The DOI matches its Crossref record; 57 of the 65 references it cites were found in a registry or an index; none of the 60 sources its claims cite is checked for support yet.
Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia
Open accessAbstract
The brain has emerged as a target for the insulin-sensitizing effects of several hormonal and nutrient-related signals. The current studies were undertaken to investigate mechanisms whereby leptin lowers circulating blood glucose levels independently of insulin. After extending previous evidence that leptin infusion directly into the lateral cerebral ventricle ameliorates hyperglycemia in rats with streptozotocin-induced uncontrolled diabetes mellitus, we showed that the underlying mechanism is independent of changes of food intake, urinary glucose excretion, or recovery of pancreatic β-cells. Instead, leptin action in the brain potently suppresses hepatic glucose production while increasing tissue glucose uptake despite persistent, severe insulin deficiency. This leptin action is distinct from its previously reported effect to increase insulin sensitivity in the liver and offers compelling evidence that the brain has the capacity to normalize diabetic hyperglycemia in the presence of sufficient amounts of central nervous system leptin.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
In streptozotocin-induced uncontrolled diabetic rats, intracerebroventricular leptin normalized blood glucose by day 7 independently of food intake, urinary glucose loss, or pancreatic β-cell recovery. The effect involved insulin-independent suppression of hepatic glucose production and increased tissue glucose uptake, with normalization of plasma glucagon and corticosterone.
Key findings
- Intracerebroventricular leptin (1 g/d) normalized blood glucose by day 7 in STZ-diabetic rats, whereas subcutaneous leptin at the same dose did not; pair feeding to leptin-treated intake also did not attenuate hyperglycemia.
- Urinary glucose was undetectable in icv leptin-treated diabetic rats versus marked glycosuria in STZ-veh rats; plasma insulin remained very low, pancreatic preproinsulin mRNA was reduced by >95%, and glucose tolerance was near normal despite no increase in circulating insulin.
- Tracer studies showed icv leptin reduced glucose appearance/HGP to nondiabetic values and increased glucose uptake in red gastrocnemius muscle, brain, BAT, and heart; during a hyperglycemic clamp at approximately 210 mg/dl, HGP was suppressed and glucose utilization increased despite severe insulin deficiency.
- Hepatic G6Pase and Pepck expression was reduced by icv leptin; plasma glucagon and corticosterone elevations in STZ diabetes were prevented by icv leptin; hepatic Igfbp2 mRNA was increased >25-fold in diabetic rats and further increased by leptin, which the authors argue is unlikely to explain the HGP effect.
Methods
- Adult male Wistar rats received two daily sc injections of STZ (40 mg/kg body weight) to induce uncontrolled diabetes, plus lateral ventricle cannula and sc osmotic minipump for icv vehicle or leptin (1 g/d) for up to 11 days; five groups (n = 7–9 per group): veh-veh, STZ-veh, STZ-leptin, STZ-veh-pair-fed, and STZ-leptin-sc.
- Daily food intake, body weight, water intake, and blood glucose were measured; ip glucose tolerance tests (2 g/kg) were performed on day 9; arterial catheters were used for plasma glucagon, corticosterone, and catecholamine measurements.
- Glucose turnover was assessed with [3-3H]glucose and 2[14C]deoxyglucose tracer dilution, including a hyperglycemic clamp at approximately 210 mg/dl; hepatic gene expression was measured by real-time PCR, and liver triglyceride/glycogen and body composition were also analyzed.
Limitations
- The paper states that Rd could not be compared between icv leptin-treated and veh-treated STZ-diabetic rats because glycosuria confounds Rd; it also states that whether reduced glucagon contributes to, or results from, leptin-mediated resolution of hyperglycemia is unknown, and that mechanisms of leptin regulation of the hypothalamic-pituitary-adrenal axis remain incompletely understood.
- The paper states that autonomic/SNS involvement is suspected but not directly tested here; it notes that prior denervation or adrenergic blockade studies did not measure Rg.
- Evident from the text: findings are limited to male Wistar rats with STZ-induced diabetes and short-term central leptin infusion, so human type 1 diabetes and long-term outcomes are not established; causal roles of glucagon and corticosterone normalization are not definitively separated from other mechanisms.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Plasma corticosterone levels were similarly elevated in animals with STZ diabetes, a response also prevented by icv leptin but not PF (Fig. 6B).”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > CNS leptin infusion normalizes plasma glucagon and corticosterone levels in STZ-induced diabetes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although the action of leptin in the CNS was also associated with normalization of elevated plasma glucagon levels, consistent with an earlier report (4), our data suggest that factors, in addition to glucagon, contribute to the glucoselowering effect of CNS leptin action.”
- Also stated in: § CNS leptin infusion normalizes plasma glucagon and corticosterone levels in STZ-induced diabetes · plain
“the elevation in plasma glucagon levels observed in STZ-treated animals was prevented by central leptin administration (Fig. 6A).”
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Also stated in: § CNS leptin infusion normalizes plasma glucagon and corticosterone levels in STZ-induced diabetes · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“leptin action in the brain potently suppresses hepatic glucose production while increasing tissue glucose uptake despite persistent, severe insulin deficiency.”
- Also stated in: § Effect of icv leptin infusion on HGP and glucose uptake in STZ-induced diabetes · plain
“glucose uptake was significantly increased in red gastrocnemius muscle and brain in STZdiabetic animals that received icv leptin relative to veh (Fig. 3C).”
- Also stated in: § Discussion · boosted
“we demonstrate that leptin acts in the CNS to potently inhibit glucose production and simultaneously increase tissue glucose utilization in diabetic animals.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Effect of icv leptin infusion on HGP and glucose uptake in STZ-induced diabetes · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we showed that the underlying mechanism is independent of changes of food intake, urinary glucose excretion, or recovery of pancreatic -cells.”
- Also stated in: § CNS leptin infusion normalizes blood glucose levels in STZ-induced diabetes · plain
“This effect was due neither to a leptin-mediated reversal of diabetic hyperphagia, because hyperglycemia was not attenuated in STZ-veh-PF animals”
- Also stated in: § Discussion · plain
“via a mechanism that cannot be explained by reduced food intake, increased urinary glucose losses, or recovery of pancreatic -cells”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § CNS leptin infusion normalizes blood glucose levels in STZ-induced diabetes · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“leptin action in the brain potently suppresses hepatic glucose production while increasing tissue glucose uptake despite persistent, severe insulin deficiency.”
- Also stated in: § Effect of icv leptin infusion on HGP and glucose uptake in STZ-induced diabetes · hedged
“Central leptin administration dramatically reduced Ra to nondiabetic control values (Fig. 3A), strongly suggesting that normalization of diabetic hyperglycemia resulted, at least in part, from reduced HGP.”
- Also stated in: § Discussion · boosted
“we demonstrate that leptin acts in the CNS to potently inhibit glucose production and simultaneously increase tissue glucose utilization in diabetic animals.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Effect of icv leptin infusion on HGP and glucose uptake in STZ-induced diabetes · hedged
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“By comparison, hepatic expression of these genes was significantly reduced in STZ-diabetic rats receiving icv leptin”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > Effect of icv leptin infusion on HGP and glucose uptake in STZ-induced diabetes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we showed that the underlying mechanism is independent of changes of food intake, urinary glucose excretion, or recovery of pancreatic -cells.”
- Also stated in: § Potential mechanism(s) mediating the glucose-lowering action of CNS leptin · plain
“the severe insulin deficiency (under both basal and glucose-stimulated conditions) caused by STZ-induced -cell destruction was not ameliorated by icv leptin.”
- Also stated in: § Discussion · plain
“via a mechanism that cannot be explained by reduced food intake, increased urinary glucose losses, or recovery of pancreatic -cells”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Potential mechanism(s) mediating the glucose-lowering action of CNS leptin · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“nor to a peripheral effect of leptin, because sc infusion of leptin at the same dose did not affect blood glucose in STZ-diabetic rats (Fig. 1D).”
- Also stated in: § Discussion · plain
“does not involve a peripheral action of leptin.”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > CNS leptin infusion normalizes blood glucose levels in STZ-induced diabetes
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we showed that the underlying mechanism is independent of changes of food intake, urinary glucose excretion, or recovery of pancreatic -cells.”
- Also stated in: § Potential mechanism(s) mediating the glucose-lowering action of CNS leptin · plain
“urinary glucose was undetectable in diabetic animals that received icv leptin similar to nondiabetic controls, whereas STZ-veh-treated animals displayed the expected, marked glycosuria (Fig. 2A).”
- Also stated in: § Discussion · plain
“via a mechanism that cannot be explained by reduced food intake, increased urinary glucose losses, or recovery of pancreatic -cells”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Potential mechanism(s) mediating the glucose-lowering action of CNS leptin · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“hepatic expression of the key gluconeogenic genes G6Pase and Pepck were markedly increased in the liver of STZ-veh-treated animals relative to nondiabetic controls (Fig. 4, A and B).”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > Effect of icv leptin infusion on HGP and glucose uptake in STZ-induced diabetes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 16
- Probably not a substantial claim. 4
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“plasma levels of NEFAs and ketone bodies were also elevated in STZ-veh animals and normalized with icv leptin administration but only after blood glucose levels had returned to normal (Fig. 6, E and F).”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > CNS leptin infusion normalizes plasma glucagon and corticosterone levels in STZ-induced diabetes
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“water intake was markedly increased in both groups of STZ-veh-treated animals, owing to the dehydrating effect of pronounced glycosuria in uDM (26), whereas water intake in diabetic animals receiving icv leptin was equivalent to that of nondiabetic controls (Fig. 2B).”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > Potential mechanism(s) mediating the glucose-lowering action of CNS leptin
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“leptin-treated STZ-diabetic rats exhibited similar weight loss to STZ-diabetic rats receiving icv veh but exhibited a greater loss of fat mass (Supplemental Fig. 1”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > CNS leptin infusion normalizes blood glucose levels in STZ-induced diabetes
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In nondiabetic animals, plasma insulin and C-peptide levels were significantly increased during the hyperglycemic clamp (P Ͻ 0.05) (Fig. 5, A and B), resulting in complete suppression of HGP and enhancement of glucose utilization by more than 250% (Fig. 5, E-H).”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > Effect of icv leptin infusion on HGP and glucose uptake in STZ-induced diabetes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Similarly, despite persistent, severe insulin deficiency, HGP was suppressed and glucose utilization was increased in STZ-diabetic rats receiving icv leptin, although less than that observed in nondiabetic animals (Fig. 5, E-H).”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > Effect of icv leptin infusion on HGP and glucose uptake in STZ-induced diabetes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“food intake was significantly increased by d 5 after STZ administration in diabetic animals receiving icv veh, and this effect was completely blocked by icv leptin (Fig. 1C).”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > CNS leptin infusion normalizes blood glucose levels in STZ-induced diabetes
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“We recently observed that in rats with STZ diabetes, physiological leptin replacement is sufficient to normalize plasma glucagon levels but has little effect on diabetic hyperglycemia (20).”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > Discussion
What the sources say
- Not checked yetcites [20] German, 2010, Leptin deficiency causes insulin resistance induced by uncontrolled diabetes., Diabetes source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“CNS leptin suppresses HGP and increases glucose utilization in uDM during a hyperglycemic clamp.”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“CNS leptin normalizes plasma glucagon and corticosterone levels in uDM.”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Although accumulating evidence suggests that leptin (10 -13), insulin (14,15), and nutrient-related signals (16 -18) in the CNS improve hepatic insulin sensitivity”
What the sources say
- Not checked yetcites [10] Liu, 1998, Intracerebroventricular leptin regulates hepatic but not peripheral glucose fluxes., J Biol Chem source
- Not checked yetcites [11] Pocai, 2005, Central leptin acutely reverses diet-induced hepatic insulin resistance., Diabetes source
- Not checked yetcites [12] Park, 2008, Long-term effects of central leptin and resistin on body weight, insulin resistance, and β-cell function and mass by the modulation of hypothalamic leptin and insulin signaling., Endocrinology source
- Not checked yetcites [13] German, 2009, Hypothalamic leptin signaling regulates hepatic insulin sensitivity via a neurocircuit involving the vagus nerve., Endocrinology source
- Not checked yetcites [14] Obici, 2002, Hypothalamic insulin signaling is required for inhibition of glucose production., Nat Med source
- Not checked yetcites [15] Pocai, 2005, Hypothalamic K(ATP) channels control hepatic glucose production., Nature source
- Not checked yetcites [16] Obici, 2002, Central administration of oleic acid inhibits glucose production and food intake., Diabetes source
- Not checked yetcites [17] Lam, 2005, Hypothalamic sensing of circulating fatty acids is required for glucose homeostasis., Nat Med source
- Not checked yetcites [18] Pocai, 2005, A brain-liver circuit regulates glucose homeostasis., Cell Metabolism source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Several lines of evidence suggest that like leptin, insulin action in the brain of nondiabetic animals lowers ambient glycemia by increasing hepatic insulin sensitivity (14,15).”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > Discussion
What the sources say
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“leptin adminis-tration directly into the brain normalizes blood glucose in rats with uDM (5)(6)(7)(8)(9) at doses that are ineffective when administered peripherally.”
What the sources say
- Not checked yetcites 5)(6)(7)(8)(9
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data suggest that icv leptin treatment reduces food intake and stimulates energy expenditure”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > CNS leptin infusion normalizes blood glucose levels in STZ-induced diabetes
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“we recently reported that in rats with STZ diabetes, physiological leptin replacement is sufficient to normalize cir-culating glucagon and corticosterone levels, yet does not reverse hyperglycemia (20).”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > CNS leptin infusion normalizes plasma glucagon and corticosterone levels in STZ-induced diabetes
What the sources say
- Not checked yetcites [20] German, 2010, Leptin deficiency causes insulin resistance induced by uncontrolled diabetes., Diabetes source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“hepatic Igfbp-2 expression is tonically inhibited by insulin and hence dramatically up-regulated by insulin deficiency (50 -52).”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > Discussion
What the sources say
- Not checked yetcites [50] Böni-Schnetzler, 1990, Insulin regulates the expression of the insulin-like growth factor binding protein 2 mRNA in rat hepatocytes., Mol Endocrinol source
- Not checked yetcites [51] Ooi, 1992, Post-transcriptional regulation of insulin-like growth factor binding protein-2 mRNA in diabetic rat liver., Biochem Biophys Res Commun source
- Not checked yetcites [52] White, 1993, Insulin-like growth-factor binding protein (IGFBP) serum levels and hepatic IGFBP-2 and -3 mRNA expression in diabetic and insulin-treated swine (Sus scrofa)., Comp Biochem Physiol B source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“conditions associated with leptin deficiency, such as fasting and uDM, clearly raise corticosterone levels via a mechanism that can be reversed with leptin treatment (44,45,49).”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > Discussion
What the sources say
- Not checked yetcites [44] Schwartz, 1997, Evidence that elevated plasma corticosterone levels are the cause of reduced hypothalamic corticotrophin-releasing hormone gene expression in diabetes., Regul Pept source
- Not checked yetcites [45] Strack, 1995, Glucocorticoids and insulin: reciprocal signals for energy balance., Am J Physiol
- Not checked yetcites [49] Ahima, 1996, Role of leptin in the neuroendocrince response to fasting., Nature source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“suggesting a shared neuronal mechanism mediating effects of both hormones on glucose metabolism (34,35).”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > Discussion
What the sources say
- Not checked yetcites [34] Obici, 2002, Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats., Nat Neurosci source
- Not checked yetcites [35] Morton, 2005, Leptin regulates insulin sensitivity via phosphatidylinositol-3-OH kinase signaling in mediobasal hypothalamic neurons., Cell Metab source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These observations are distinct from any previously described CNS leptin action”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
In the paper
“nor was activation of the 3-adrenergic receptors required or sufficient to mediate the effects of leptin on blood glucose levels (7)”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > Discussion
What the sources say
- Not checked yetcites [7] da Silva, 2006, Chronic antidiabetic and cardiovascular actions of leptin: role of CNS and increased adrenergic activity., Am J Physiol Regul Integr Comp Physiol source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Based on these data, we infer that icv leptin normalizes blood glucose levels in STZ-diabetic rats at least in part via an insulin-independent mechanism that increases glucose utilization in tissues such as BAT and skeletal muscle.”
§ Leptin Activates a Novel CNS Mechanism for Insulin-Independent Normalization of Severe Diabetic Hyperglycemia > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The authors state this as an assumption.
How CNS leptin signaling normalizes diabetic hyperglycemia in uDM, and whether this involves leptin-dependent effects on HGP or Rg, is unknown.
“how CNS leptin signaling normalizes diabetic hyperglycemia in uDM, and whether this involves leptin-dependent effects on hepatic glucose production (HGP) or tissue glucose uptake (Rg), is unknown.”
The paper relies on this without support.
Changes in plasma glucagon do not affect glucose utilization.
“an effect not readily explained by changes of plasma glucagon (which does not affect glucose utilization)”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“we recently found that continuous infusion of leptin directly into the brain normalizes blood glucose levels in STZ-induced diabetic rats via a mechanism that cannot be explained by reduced food intake, increased urinary glucose losses or a recovery of pancreatic β-cells.”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [67]
In the citing paper
“This leptin action is distinct from its previously reported effect to increase insulin sensitivity in the liver (66, 146), and offers compelling evidence of a novel mechanism through which the brain normalizes diabetic hyperglycemia without the need for insulin (67).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [67]
In the citing paper
“Instead, leptin action in the brain potently suppressed hepatic glucose production while increasing tissue glucose uptake despite persistent, severe insulin deficiency (67).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [67]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Incorrect figure panel cited for norepinephrine
MinorThe text cites Figure 6A for norepinephrine, but the figure caption identifies panel A as glucagon and panel C as norepinephrine.
“Although changes in plasma norepinephrine and epinephrine levels are unlikely to explain leptin's effects (Fig. 6, A and D)”
“Plasma glucagon (A), plasma corticosterone (B), norepinephrine (NE) (C), epinephrine (EPI) (D)”
Citations
Cites
The rat brain in stereotaxic coordinates
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Role of leptin in the neuroendocrine response to fasting
Ahima, R. S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., & Flier, J. S. (1996) · Nature · doi:10.1038/382250a0 · Cited by 3,117
Hypothalamic insulin signaling is required for inhibition of glucose production
Obici, S., Zhang, B. B., Karkanias, G., & Rossetti, L. (2002) · Nature Medicine · doi:10.1038/nm1202-798 · Cited by 904
Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats
Obici, S., Feng, Z., Karkanias, G., Baskin, D. G., & Rossetti, L. (2002) · Nature Neuroscience · doi:10.1038/nn0602-861 · Cited by 719
RIZZA, R. A., MANDARINO, L. J., & GERICH, J. E. (1982) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-54-1-131 · Cited by 696
Central Administration of Oleic Acid Inhibits Glucose Production and Food Intake
Obici, S., Feng, Z., Morgan, K., Stein, D., Karkanias, G., & Rossetti, L. (2002) · Diabetes · doi:10.2337/diabetes.51.2.271 · Cited by 654
Hypothalamic KATP channels control hepatic glucose production
Pocai, A., Lam, T. K. T., Gutierrez-Juarez, R., Obici, S., Schwartz, G. J., Bryan, J., Aguilar-Bryan, L., & Rossetti, L. (2005) · Nature · doi:10.1038/nature03439 · Cited by 645
Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats
Obici, S., Feng, Z., Karkanias, G. B., et al. (2002) · Nature Neuroscience · doi:10.1038/nn861 · Cited by 572
DeFronzo, R. A., Simonson, D. C., & Ferrannini, E. (1982) · Diabetologia · doi:10.1007/bf00253736 · Cited by 539
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8 of the 65 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Maghnie, 2003, Diabetes insipidus., Horm Res, 59, 42
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Items 101–169 of 169
Denroche, H. C., Kwon, M., Glavas, M. M., Tudurí, E., Philippe, M., Quong, W. L., & Kieffer, T. J. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.06.009 · Cited by 13
Role of autonomic nervous system in chronic CNS-mediated antidiabetic action of leptin
da Silva, A. A., Hall, J. E., Moak, S. P., Browning, J. R., Houghton, H. J., Micheloni, G. C., & do Carmo, J. M. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00301.2016 · Cited by 13
“However, we (6) and others (13) have demonstrated that the antidiabetic effects of leptin are largely independent of its anorexic effect.”
BackgroundInfluentialChanges in Satiety Hormones in Response to Leptin Treatment in a Patient with Leptin Deficiency
Roth, C. L., von Schnurbein, J., Elfers, C., Moß, A., & Wabitsch, M. (2018) · Hormone Research in Paediatrics · doi:10.1159/000489884 · Cited by 13
Distinct Roles for Brain and Pancreas in Basal and Postprandial Glucose Homeostasis
Alonge, K. M., Porte, D., & Schwartz, M. W. (2023) · Diabetes · doi:10.2337/db22-0969 · Cited by 13
Self-citationSingha, A. K., Yamaguchi, J., Gonzalez, N. S., Ahmed, N. I., Toney, G. M., & Fujikawa, T. (2019) · Endocrinology · doi:10.1210/en.2018-00907 · Cited by 11
The Adipokine Profile and the Cardiometabolic Risk in Non-Obese Young Adults
Oțelea, M. R., Streinu‐Cercel, A., Băicuş, C., & Nițescu, M. (2019) · Balkan Medical Journal · doi:10.4274/balkanmedj.galenos.2018.2018.0789 · Cited by 12
“In patients with type 2 diabetes, AIP was strongly associated with markers of impaired glucose metabolism (27).”
BackgroundSingha, A. K., Palavicini, J. P., Pan, M., Farmer, S., Sandoval, D. A., Han, X., & Fujikawa, T. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.588447 · Cited by 10
AgRP neuron hyperactivity drives hyperglycemia in a mouse model of type 2 diabetes
Gou, Y., Glat, M. J., Damian, V. M., Bryan, C. L., Phan, B. A., Faber, C. L., Trivedi, A., Hwang, M. K., Scarlett, J. M., Morton, G. J., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci189842 · Cited by 13
“…potently inhibiting Mc4r signaling, this combination is implicated in the hyperphagia, obesity, and diabetes of leptin-deficient models, and reversal of this effect is implicated in the restoration of euglycemia to diabetic animals following central administration of either leptin (33) or FGF1 (5).”
Self-citationZouhar, P., Rakipovski, G., Bokhari, M. H., Busby, O., Paulsson, J. F., Conde‐Frieboes, K. W., Fels, J. J., Raun, K., Andersen, B., Cannon, B., et al. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00253.2019 · Cited by 10
“Although leptin does not directly activate BAT thermogenesis in normal mice (12), it induces glucose uptake into BAT in type 1 diabetic animals (15).”
BackgroundChronic CNS-mediated cardiometabolic actions of leptin: potential role of sex differences
da Silva, A. A., Pinkerton, M., Spradley, F. T., Palei, A. C., Hall, J. E., & do Carmo, J. M. (2020) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00027.2020 · Cited by 10
Leptin and Insulin in COPD: Unveiling the Metabolic-Inflammatory Axis—A Narrative Review
Catană, O. M., Nemeş, A. F., Cioboată, R., Toma, C., Mitroi, D. M., Călăraşu, C., & Streba, C. T. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14082611 · Cited by 11
“It is noteworthy that certain antidiabetic medications (metformin, pioglitazone, sitagliptin, liraglutide, and empagliflozin) have demonstrated the capacity to lower leptin levels [225,226], yet the comprehensive clinical implications of these medications remain to be fully elucidated.”
Khan, M. M. (2022) · World Journal of Psychiatry · doi:10.5498/wjp.v12.i6.827 · Cited by 9
Harris, R. B. S. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00143.2021 · Cited by 9
Mirrakhimov, E. M., Bektasheva, E., Isakova, J. T., et al. (2023) · Archives of Medical Science · doi:10.5114/aoms/170121 · Cited by 8
Szilvássy, Z., Németh, J., Kovacs, P. L., Paragh, G., Sári, R. Z., Vı́gh, L., & Peitl, B. (2011) · Metabolism · doi:10.1016/j.metabol.2011.10.010 · Cited by 8
Leptin concentrations in type 2 diabetes and non-diabetes Nigerian-Africans.
Onyemelukwe, O. U., Ogoina, D., & Onyemelukwe, G. C. (2020) · PubMed Central · Cited by 8
Neuroendocrine Control of Body Energy Homeostasis
Affinati, A. H., & Myers, M. G. (2021) · Europe PMC (PubMed Central) · Cited by 8
Leptin, GABA, and Glucose Control
Kahn, B. B., & Minokoshi, Y. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.08.015 · Cited by 8
“Leptin increases glucose utilization in peripheral tissues, suppresses hepatic glucose production, and reverses hyperglucagonemia in insulin-deficient rodents (German et al., 2011; Wang et al., 2010) (Figure 1).”
BackgroundBrain Defense of Glycemia in Health and Diabetes
Mirzadeh, Z., & Faber, C. L. (2024) · Diabetes · doi:10.2337/dbi24-0001 · Cited by 8
Bektur, E., Şahin, E., & Bayçu, C. (2019) · Europe PMC (PubMed Central) · doi:10.22038/ijbms.2019.34529.8190 · Cited by 7
“Leptin infusion or gene therapy, can reverse hyperglycemia without a detectable rise in circulating insulin levels in STZ-treated rats (33) and mice (45), nonobese diabetic (NOD) mice (46), insulin deficient Akita mice (46) and BioBreeding rats with virally-induced beta cell destruction.”
BackgroundMeek, T. H., Matsen, M. E., Faber, C. L., Samstag, C. L., Damian, V. M., Hồng, N. T., Scarlett, J. M., Flak, J. N., Myers, M. G., & Morton, G. J. (2018) · Endocrinology · doi:10.1210/en.2017-03199 · Cited by 7
Self-citationToward the Decipherment of Molecular Interactions in the Diabetic Brain
Chomová, M. (2022) · Biomedicines · doi:10.3390/biomedicines10010115 · Cited by 8
“The continuous infusion of leptin at supraphysiological doses directly into the brains of T1DM rats led to blood glucose normalization [38].”
BackgroundGlucoregulatory responses to hypothalamic preoptic area cooling
Muta, K., Matsen, M. E., Acharya, N., Stefanovski, D., Bergman, R. N., Schwartz, M. W., & Morton, G. J. (2019) · Brain Research · doi:10.1016/j.brainres.2019.01.002 · Cited by 6
“For studies involving frequently sampled glucose tolerance tests (FSIGTs), rats underwent surgical implantation of indwelling catheters (Instech Laboratories, Inc., PA) into the jugular vein and carotid artery as previously described (German et al., 2011; Morton et al., 2017; Rojas et al., 2015).”
MethodSelf-citationReno, C. M., Ding, Y., & Sherwin, R. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00361.2015 · Cited by 6
Liu, X.-W., Yin, J., Ma, Q.-S., Qi, C., Mu, J.-Y., Zhang, L., Gao, L., & Jing, Y. (2017) · High Altitude Medicine & Biology · doi:10.1089/ham.2016.0141 · Cited by 5
“…present in the arcuate nucleus, including growth hormone-releasing factor neurons, endorphin neurons, P-substance neurons, NYP neurons, POMC neurons, melano-FIG cortin neurons, dopamine neurons, and GABA neurons (Coppari et al., 2005; Huo et al., 2009; German et al., 2011; Berglund et al., 2012).”
Central leptin pathways in metabolic homeostasis
Zhao, Y., Laule, C. F., & Rahmouni, K. (2025) · Clinical Science · doi:10.1042/cs20257748 · Cited by 5
“These reductions in systemic glucose were associated with increased glucose uptake by peripheral organs [166].”
Efeito da redução de ninhada sobre as respostas autonômicas e metabólicas de ratos Wistar
Rinaldi, W., Ribeiro, T. A., MINCACHE, A. S. M., Fabricio, G. S., Tófolo, L. P., Gomes, R. M., Mendes, F. C. V., & Mathias, P. C. D. F. (2012) · Revista de Nutrição · doi:10.1590/s1415-52732012000300002 · Cited by 5
da Silva, A. A., Hall, J. E., Dai, X., Wang, Z., Salgado, M. C., & do Carmo, J. M. (2021) · Diabetes · doi:10.2337/db21-0126 · Cited by 4
The Role of Brain in Glucose Metabolism
Obici, S., & Martins, P. J. F. (2009) · Springer eBooks · doi:10.1007/978-0-387-09841-8_6 · Cited by 5
Mildner, M., Müller‐Fielitz, H., Stölting, I., Jöhren, O., Steckelings, U. M., & Raasch, W. (2017) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-017-1346-7 · Cited by 3
An acute method to test leptin responsiveness in rats
Desai, B. N., & Harris, R. B. S. (2014) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00548.2013 · Cited by 3
“leptin infusions in our experiments had no effect on glucagon levels measured at the end of the 302 infusion in normal and sucrose rats in spite of emerging evidence of the inhibitory effect of leptin on glucagon secretion 303 and circulating glucagon levels (6, 8, 35, 36).”
BackgroundA role for leptin-regulated neurocircuitry in subordination stress
Flak, J. N. (2016) · Physiology & Behavior · doi:10.1016/j.physbeh.2016.11.019 · Cited by 3
Ahima, R. S., Scolaro, L. M., & Park, H.-K. (2016) · Springer eBooks · doi:10.1007/978-3-319-11251-0_24 · Cited by 5
An unexpected role for the brain in the pathogenesis of diabetic ketoacidosis
Mirzadeh, Z., Morton, G. J., Hirsch, I. B., & Schwartz, M. W. (2025) · Journal of Clinical Investigation · doi:10.1172/jci196357 · Cited by 2
“…we and others made an unexpected discovery: In rodent models of uncontrolled type 1 diabetes (T1D), the most severe manifestations of insulin deficiency — hyperglycemia and diabetic ketoacidosis (DKA) — can be fully reversed by infusing the adipocyte hormone leptin directly into the brain (1, 2).”
Self-citationSystemic Glucose Regulation by a Hindbrain Inhibitory Circuit in a Mouse Model of Type 1 Diabetes
Juras, J. A., Pitra, S., & Smith, B. N. (2024) · Neuroendocrinology · doi:10.1159/000536142 · Cited by 2
“Early investigation focused on hypothalamic nuclei, into which injection of insulin, glucose, or leptin decreases systemic blood glucose levels [8 – 10], while deletion of insulin or leptin receptors decreases glucose tolerance and leads to insulin resistance [11, 12].”
BackgroundModelling remission from overweight type 2 diabetes reveals how altering advice may counter relapse
Sweatman, C. Z. W. H. (2024) · Mathematical Biosciences · doi:10.1016/j.mbs.2024.109180 · Cited by 2
Systemic Glucose Homeostasis Requires Pancreatic but Not Neuronal ATP-sensitive Potassium Channels
Li, A. H., Tsai, W.-S., Tsai, W.-H., & Yang, S. (2025) · Function · doi:10.1093/function/zqaf002 · Cited by 2
Ahima, R. S., Scolaro, L. M., & Park, H.-K. (2015) · Springer eBooks · doi:10.1007/978-3-319-12125-3_24-1 · Cited by 2
Neuroendocrine Control of Energy Stores
Cone, R. D., & Elmquist, J. K. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-29738-7.00035-6 · Cited by 2
THE RELATIONSHIP THE LEPTIN HORMONE, OBESITY AND DIABETES
Sarı, A., & Sadeq, M. B. (2020) · NWSA Academic Journals · doi:10.12739/nwsa.2020.15.2.3a0095 · Cited by 2
The role of brain in the regulation of glucose homeostasis
Lyngdoh, J., Marbaniang, E., Lynrah, K. G., & Lyngdoh, M. (2015) · International Journal of Medical Science and Public Health · doi:10.5455/ijmsph.2015.25072015364 · Cited by 1
Kim, S., & Kim, D. (2012) · InTech eBooks · doi:10.5772/51795 · Cited by 1
“Leptin is transported across the blood brain barrier (BBB) by binding to its receptor in the arcuate nucleus of the hypothalamus to regulate glucose metabolism via central leptin signaling, which modulates sympathetic and neuroendocrine activities [126, 127], as well as though peripheral signaling in insulin-sensitive…”
BackgroundGlucose handling by the brain and its implication in metabolic syndrome
Mukhopadhyay, R., Chowdhury, A. S., & Palui, R. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-85732-1.00083-9 · Cited by 1
Leptina: descripción de su intrigante biología. Una revisión. Parte I
López-Dionicio, Y. I., Ortíz-Flores, M., Hidalgo, I., Ortiz-Vilchis, P., Guevara, G., Nájera, N., Ceballos, G. M., & Meaney, E. (2025) · Cardiovascular and Metabolic Science · doi:10.35366/119633 · Cited by 1
Fu, L., Sugiyama, M., Kamal, S., Ide, T., Takeda, T., Kuno, M., Takagi, H., Koike, T., Arima, H., & Banno, R. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26104595 · Cited by 4
“Notably, intracerebroventricular leptin administration has been shown to normalize glucose metabolism in rodent models of T1DM in the absence of insulin [11,12].”
InfluentialBiomarkers of Insulin Resistance
Cox‐York, K. A., & Pereira, R. I. (2019) · Contemporary Endocrinology · doi:10.1007/978-3-030-25057-7_11 · Cited by 1
Beyene, Z. (2021) · Zenodo (CERN European Organization for Nuclear Research) · doi:10.47191/ijpbms/v1-i7-02 · Cited by 1
Elucidating the Roles of TCAP-1 on Glucose Transport and Muscle Physiology
Chen, Y. (2014) · TSpace (University of Toronto) · Cited by 1
Paracrine signaling by pancreatic δ cells determines the glycemic set point in micePreprint
Huang, J. L., Lee, S. C. L., Pourhosseinzadeh, M. S., Krämer, N., Guillen, J. V., Cinque, N., Aniceto, P. A., Koike, S., & Huising, M. O. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.06.29.496132 · Cited by 1
Leptin and Intermediary Metabolism: Focus on Glucoregulation and Lipids
Morgan, R. C., & Considine, R. V. (2014) · Springer eBooks · doi:10.1007/978-3-319-09915-6_7
MicroRNA-mediated regulation of Cadm1 contributes to beta cell function and energy homeostasis
Rathjen, T. (2015) · Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver · doi:10.17169/refubium-6345
Histomorphometric analysis of the effects of calcitonin on alveolar socket repair in diabetic rats
Delgado, A. D. M., Gomes, M. F., Amorim, J. B. O., et al. (2012) · Brazilian Dental Science · doi:10.14295/bds.2012.v15i2.763
Control of Appetite/Satiety and Energy Balance
Elmquist, J. K., & Horton, J. D. (2015) · Wiley eBooks · doi:10.1002/9781118512074.ch28
Cheng, L. (2015) · Research Online (University of Wollongong)
The Role Of Adipose Tissue In Glucose Homeostasis
Lyngdoh, J., Marbaniang, E., & Sangma, M. (2016) · International Journal Of Medical Science And Clinical Invention · doi:10.18535/ijmsci/v3i9.01
“Besides increasing insulin sensitivity, leptin has also been found to lower glucose level by reducing the levels of counter-regulatory hormones like growth hormones, corticosterone and even glucagon in insulin deficient rodents [27,33,34].”
BackgroundThe metabolic effects of leptin therapy and glucagon suppression therapy in mouse models of diabetes
Neumann, U. H. (2017) · cIRcle (University of British Columbia) · doi:10.14288/1.0348695
“Lastly, insulin-deficient rodents, which had depleted WAT depots, exhibited hyperglycemia, insulin resistance, and impaired glucose tolerance, all of which were improved by leptin therapy [167, 176, 177, 230-235].”
BackgroundInfluentialCNS hormonal and nutritional regulation of glucose and energy homeostasis
Abraham, M. A. (2017) · TSpace (University of Toronto)
Estudo das funções da leptina durante o período intrauterino e infância no camundongo.
Lobo, A. M. R. (2019) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2019.tde-21032019-161135
Biodiversity of the Adipocyte-Derived Hormone, Leptin
Manjunathan, R., Kasiviswanathan, D., & Jayaraman, S. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.100576
“The cytokine enhances neovascularization through VEGF in many cancerous conditions [102, 103].”
BackgroundThe Role of Brain in Glucose Metabolism
Obici, S., & Martins, P. J. F. (2016) · Springer eBooks · doi:10.1007/978-3-319-20797-1_6-1
Ahima, R. S., Scolaro, L. M., & Park, H.-K. (2017) · Springer eBooks · doi:10.1007/978-3-319-12125-3_24-2
The Role of Brain in Glucose Metabolism
Obici, S., & Martins, P. J. F. (2017) · Springer eBooks · doi:10.1007/978-3-319-18741-9_6
Zakharova, I. O., Bayunova, L. V., Derkach, K. V., Ilyasov, I. O., Morina, I. Y., Shpakov, A. O., & Avrova, N. F. (2022) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093022060072
Is Diabetes Pre-coded in the Brain? Role of Hypothalamus, Addiction Network and Social Cognition
Chatterjee, S., Dubey, S., Ghosh, R., & Bhattacharjee, R. (2023) · Asian Journal of Diabetology · doi:10.59793/ajd.v24i2.541
Aravindakshan, M. R., Ghosh, D., Mandal, C., Sarkar, J., Maity, S. K., & Chakrabarti, P. (2024) · medRxiv · doi:10.1101/2024.06.18.24309097
“The augmentations carried out in the OMM are as follows: • leptin-induced glucose absorption in peripheral tissues independent of insulin[5, 33], • leptin-induced inhibition of insulin secretion [7], • leptin production from adipose tissue modelled through BMI.”
BackgroundNi, W., Shen, Y., Shichao, L., Liu, S., Sun, L., Zhao, D., Dong, Z., Wang, S., Wang, W., & Liu, M. (2025) · Food Frontiers · doi:10.1002/fft2.70139
Cardiometabolic regulation by adipocyte-derived leptin and the brain melanocortin system
Hall, J. E., Omoto, A. C. M., do Carmo, J. M., da Silva, A. A., Mouton, A. J., Wang, Z., & Hall, M. E. (2026) · Clinical Science · doi:10.1042/cs20250039
“Administration of exogenous leptin exerts powerful actions on glucose regulation, markedly increasing glucose uptake and metabolism in multiple tissues, while reducing hepatic glucose production and enhancing insulin sensitivity [109].”
Metadata
- Authors
- German, J. P., Thaler, J. P., Wisse, B. E., Oh-I, S., Sarruf, D. A., Matsen, M. E., Fischer, J. D., Taborsky, G. J., Schwartz, M. W., & Morton, G. J.
- Affiliations
- University of Washington (US)
- Diabetes and Obesity Center of Excellence (J.P.G., J.P.T., B.E.W., S.O.-I., D.A.S., M.E.M., J.D.F., M.W.S., G.J.M.), Department of Medicine, University of Washington, Seattle, Washington 98109
- VA Puget Sound Health Care System (US)
- Corresponding author
- Morton, Gregory J.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2010-12-15
- Volume
- 152
- Issue
- 2
- Pages
- 394-404
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC3037161
- OpenAlex
- W1996800212
- Semantic Scholar
- 7c46f9454e2b40dacf481b15d5c0a823b6dc64a7
- Cited by
- 169
- References
- 65
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 7 · 2023: 4 · 2022: 7 · 2021: 12 · 2020: 10 · 2019: 10 · 2018: 6 · 2017: 14 · 2016: 18 · 2015: 23 · 2014: 14 · 2013: 16 · 2012: 11
- FWCI
- 4.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- University of Washington
- National Institutes of Health (1u24dk076126-01)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK074758, DK-083042, U24-DK076126, DK 035816, DK-050154-13, R56DK050154, R01DK050154, R01DK090320, P30DK035816, R01DK083042)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, diabetic hyperglycemia, insulin-independent glucose regulation, hepatic glucose production, tissue glucose uptake, streptozotocin-induced diabetes, insulin deficiency
- MeSH terms
- Animals, Blood Glucose, Body Composition, Brain, Corticosterone, Diabetes Mellitus, Experimental, Glucagon, Glucose Tolerance Test, Hyperglycemia, Insulin, Male, Rats, Wistar, Reverse Transcriptase Polymerase Chain Reaction, Leptin, Rats
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