Marked and rapid decreases of circulating leptin in streptozotocin diabetic rats: reversal by insulin
Open accessAbstract
Evidence for regulation of circulating leptin by insulin is conflicting. Diabetes was induced in rats with streptozotocin (STZ; 40 mg ⋅ kg−1⋅ day−1× 2 days) to examine the effect of insulin-deficient diabetes and insulin treatment on circulating leptin. After 12 wk, plasma leptin concentrations in untreated rats were all <0.4 ng/ml versus 4.9 ± 0.9 ng/ml in control animals ( P < 0.005). In rats treated with subcutaneous insulin implants for 12 wk, which reduced hyperglycemia by ∼50%, plasma leptin was 2.1 ± 0.6 ng/ml, whereas leptin concentrations were 6.0 ± 1.6 ng/ml in insulin-implanted rats receiving supplemental injections of insulin for 4 days to normalize plasma glucose ( P< 0.005 vs. STZ untreated). In a second experiment, plasma leptin was monitored at biweekly intervals during 12 wk of diabetes. In rats treated with insulin implants, plasma leptin concentrations were inversely proportional to glycemia ( r= −0.64; P < 0.0001) and unrelated to body weight ( P = 0.40). In a third experiment, plasma leptin concentrations were examined very early after the induction of diabetes. Within 24 h after STZ injection, plasma insulin decreased from 480 ± 30 to 130 ± 10 pM ( P < 0.0001), plasma glucose increased from 7.0 ± 0.2 to 24.8 ± 0.5 mM, and plasma leptin decreased from 3.2 ± 0.2 to 1.2 ± 0.1 ng/ml (Δ = −63 ± 3%, P < 0.0001). In a subset of diabetic rats treated with insulin for 2 days, glucose decreased to 11.7 ± 3.9 mM and leptin increased from 0.5 ± 0.1 to 2.9 ± 0.6 ng/ml ( P< 0.01) without an effect on epididymal fat weight. The change of leptin was correlated with the degree of glucose lowering ( r = 0.75, P < 0.05). Thus insulin-deficient diabetes produces rapid and sustained decreases of leptin that are not solely dependent on weight loss, whereas insulin treatment reverses the hypoleptinemia. We hypothesize that decreased glucose transport into adipose tissue may contribute to decreased leptin production in insulin-deficient diabetes.
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At least some beneficial effects of insulin treatment in uncontrolled insulin-deficient diabetes may arise from an associated increase of leptin action because plasma leptin levels are normalized by insulin treatment in uDM rats.
“at least some of the beneficial effects of insulin treatment may in fact arise from an associated increase of leptin action since plasma leptin levels are normalized by insulin treatment in uDM rats (78).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [78]
Uncontrolled insulin-deficient diabetes is characterized by hyperglycemia and hyperphagia, progressive loss of body fat stores, and dramatic reduction of circulating leptin and insulin.
“uDM is characterized by both hyperglycemia and hyperphagia (102), with progressive loss of body fat stores, and with a dramatic reduction of circulating levels of leptin as well as insulin (78).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [78]
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“normalized by insulin treatment in uDM rats (78).”
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Self-citation
- Authors
- Havel, P. J., Uriu-Hare, J. Y., Liu, T., Stanhope, K. L., Stern, J. S., Keen, C. L., & Ahrén, B.
- Affiliations
- Lund University (SE)
- Department of Nutrition, University of California, Davis, California 95616; and Department of Medicine, Lund University, S-20502 Malmö, Sweden
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 1998-05-01
- Volume
- 274
- Issue
- 5
- Pages
- R1482-R1491
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2112457773
- Cited by
- 198
- References
- 45
- Citations by year
- 2024: 2 · 2023: 4 · 2021: 8 · 2020: 3 · 2019: 2 · 2018: 6 · 2017: 1 · 2016: 8 · 2015: 13 · 2014: 7 · 2013: 10 · 2012: 10
- FWCI
- 4.84
- Type
- journal article
- Language
- en
- Open access
- green
- escholarship.org
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (5r01dk018899-18)
- Medical Research Council
- National Cancer Institute
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-07355, T32DK007355, DK 50129, R01DK050129, DK-18899)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- leptin, insulin, streptozotocin-induced diabetes, insulin deficiency, insulin therapy, plasma leptin concentration, glycemia, hyperglycemia, leptin regulation, insulin resistance, epididymal adipose tissue, body weight, diabetes reversal, leptin resistance, adipose tissue, energy homeostasis, rats, mice
- MeSH terms
- Animals, Blood Glucose, Body Weight, Diabetes Mellitus, Experimental, Eating, Hypoglycemic Agents, Insulin, Male, Proteins, Streptozocin, Rats, Sprague-Dawley, Leptin, Rats
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