Portal glucose infusion in the mouse induces hypoglycemia: evidence that the hepatoportal glucose sensor stimulates glucose utilization.
Abstract
To analyze the role of the murine hepatoportal glucose sensor in the control of whole-body glucose metabolism, we infused glucose at a rate corresponding to the endogenous glucose production rate through the portal vein of conscious mice (Po-mice) that were fasted for 6 h. Mice infused with glucose at the same rate through the femoral vein (Fe-mice) and mice infused with a saline solution (Sal-mice) were used as controls. In Po-mice, hypoglycemia progressively developed until glucose levels dropped to a nadir of 2.3 +/- 0.1 mmol/l, whereas in Fe-mice, glycemia rapidly and transiently developed, and glucose levels increased to 7.7 +/- 0.6 mmol/l before progressively returning to fasting glycemic levels. Plasma insulin levels were similar in both Po- and Fe-mice during and at the end of the infusion periods (21.2 +/- 2.2 vs. 25.7 +/- 0.9 microU/ml, respectively, at 180 min of infusion). The whole-body glucose turnover rate was significantly higher in Po-mice than in Fe-mice (45.9 +/- 3.8 vs. 37.7 +/- 2.0 mg x kg(-1) x min)-1), respectively) and in Sal-mice (24.4 +/- 1.8 mg x kg(-1) x min(-1)). Somatostatin co-infusion with glucose in Po-mice prevented hypoglycemia without modifying the plasma insulin profile. Finally, tissue glucose clearance, which was determined after injecting 14C-2-deoxyglucose, increased to a higher level in Po-mice versus Fe-mice in the heart, brown adipose tissue, and the soleus muscle. Our data show that stimulation of the hepatoportal glucose sensor induced hypoglycemia and increased glucose utilization by a combination of insulin-dependent and insulin-independent or -sensitizing mechanisms. Furthermore, activation of the glucose sensor and/or transmission of its signal to target tissues can be blocked by somatostatin.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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 fasting and in the feeding situation, the vagus nerve is responsible for energy storage.
“Thus, in the fasting and in the feeding situation, the vagus nerve is responsible for energy storage.”
From Interaction of the endocrine system with inflammation: a function of energy and volume regulation (2014) · cites this paper as [41]
Cited by
Sorted by citations
GLUT2, glucose sensing and glucose homeostasis
Thorens, B. (2015) · Diabetologia · doi:10.1007/s00125-014-3451-1 · Cited by 722 · see citing works
“Studies of RIPGlut1;Glut2mice showed that the signal generated by glucose infusion into the portal vein and that stimulates glucose utilisation by peripheral tissues required GLUT2 expression [45, 46].”
BackgroundSelf-citationGlucose transporters in adipose tissue, liver, and skeletal muscle in metabolic health and disease
Chadt, A., & Al-Hasani, H. (2020) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-020-02417-x · Cited by 510 · see citing works
“Postprandial stimulation of the vagal afferents within the hepatoportal vein inhibits glucagon secretion from pancreatic alpha cells and, on the other hand, leads to enhanced glucose transport into muscle and adipose tissue [21, 57].”
BackgroundThe AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity
Viollet, B., Andreelli, F., Jørgensen, S. B., Perrin, C., Geloen, A., Flamez, D., Mu, J., Lenzner, C., Baud, O., Bennoun, M., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci16567 · Cited by 499 · see citing works
Self-citationPoggi, M., Bastelica, D., Gual, P., Iglesias, M. A., Grémeaux, T., Knauf, C., Peiretti, F., Verdier, M., Juhan-Vague, I., Tanti, J., et al. (2007) · Diabetologia · doi:10.1007/s00125-007-0654-8 · Cited by 351 · see citing works
“Glucose turnover studies and in vivo glucose utilisation index in individual tissues These experiments were performed as described [23, 24].”
Self-citationGlucose transport and sensing in the maintenance of glucose homeostasis and metabolic harmony
Herman, M. A. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29027 · Cited by 349 · see citing works
Isoform-specific Regulation of Insulin-dependent Glucose Uptake by Akt/Protein Kinase B
Bae, S. S., Cho, H., Mu, J., & Birnbaum, M. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306782200 · Cited by 312 · see citing works
Knauf, C. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25764 · Cited by 310 · see citing works
Heterogeneous metabolic adaptation of C57BL/6J mice to high-fat diet
Burcelin, R., Crivelli, V., Dacosta, A., Roy-Tirelli, A., & Thorens, B. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00332.2001 · Cited by 292 · see citing works
Self-citationRole of the gut-brain axis in energy and glucose metabolism
Wachsmuth, H. R., Weninger, S. N., & Duca, F. A. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00677-w · Cited by 269 · see citing works
Kupffer cell activation is a causal factor for hepatic insulin resistance
Lanthier, N., Molendi‐Coste, O., Horsmans, Y., van Rooijen, N., Cani, P. D., & Leclercq, I. A. (2009) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00391.2009 · Cited by 258 · see citing works
“Femoral iv catheter was implanted 7 days before clamp studies (4).”
Burcelin, R., Costa, A. D., Drucker, D. J., & Thorens, B. (2001) · Diabetes · doi:10.2337/diabetes.50.8.1720 · Cited by 251 · see citing works
“The active form of GLP-1 is GLP1-(7-37) or GLP-1-(7-36)amide; it is also intriguing that the half-life of GLP-1-(7-37) and GLP-1-(7-36)amide is very short (;0.”
BackgroundMethodInfluentialSelf-citationThe role of the autonomic nervous liver innervation in the control of energy metabolism
Yi, C., la Fleur, S. E., Fliers, E., & Kalsbeek, A. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.01.006 · Cited by 229 · see citing works
“needs activation of the glucagon-like peptide-1 (GLP-1) receptor [109-114], and is GLUT-2 dependent [115].”
BackgroundPreitner, F., Ibberson, M. R., Franklin, I., Binnert, C., Pende, M., Gjinovci, A., Hansotia, T., Drucker, D. J., Wollheim, C. B., Burcelin, R., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20518 · Cited by 254 · see citing works
“We have demonstrated that the function of this sensor is suppressed when the GLP-1 receptor is absent, as in Glp-1R–/– mice or when inactivated by the antagonist exendin-(9-39).”
BackgroundMethodInfluentialSelf-citationBertrand, C., Valet, P., & Castan‐Laurell, I. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00115 · Cited by 219 · see citing works
“, 2007), and an improved insulin sensitivity (Burcelin et al., 2000; Delaere et al., 2010).”
BackgroundGlucose sensing by the hepatoportal sensor is GLUT2-dependent: in vivo analysis in GLUT2-null mice.
Burcelin, R., Dolci, W., & Thorens, B. (2000) · Diabetes · doi:10.2337/diabetes.49.10.1643 · Cited by 211 · see citing works
“As a readout for the signal generated by this sensor, we used the observation reported in the accompanying article (11) that glucose infusion through the portal vein induces hypoglycemia by a mechanism that involved increased glucose utilization in a subset of tissues, which could be blocked by somatostatin.”
BackgroundMethodInfluentialSelf-citationIntestinal Cholecystokinin Controls Glucose Production through a Neuronal Network
Cheung, G. W. C., Kokorovic, A., Lam, C., Chari, M., & Lam, T. K. T. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.07.005 · Cited by 179 · see citing works
“For the neuronal regulation of glucose homeostasis by the small intestine, a hepatoportal sensor [18;19] and a gut-brain-liver [20] neuronal axis induced by glucose and lipid respectively have”
BackgroundInfluentialThe physiological control of eating: signals, neurons, and networks
Watts, A. G., Kanoski, S. E., Sanchez-Watts, G., & Langhans, W. (2022) · Physiological Reviews · doi:10.1152/physrev.00028.2020 · Cited by 168 · see citing works
Kowalski, G. M., & Bruce, C. R. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00165.2014 · Cited by 154 · see citing works
“Of note, there is evidence in mice that somatostatin is rather ineffective at inhibiting insulin secretion (32, 134), which may limit its application to the mouse.”
BackgroundWaget, A., Cabou, C., Masseboeuf, M., Cattan, P., Armanet, M., Karaca, M., Castel, J., Garret, C., Payros, G., Maida, A., et al. (2011) · Endocrinology · doi:10.1210/en.2011-0286 · Cited by 153 · see citing works
“We first demonstrated that this mechanism increased muscle glucose utilization through an insulin-independent mechanism (28); our current data reveal an imperfect correlation between the effect of sitagliptin to control glucose and changes in portal and plasma insulin levels.”
BackgroundSelf-citationCura, A. J., & Carruthers, A. (2012) · Comprehensive physiology · doi:10.1002/cphy.c110024 · Cited by 163 · see citing works
Role of Central Nervous System Glucagon-Like Peptide-1 Receptors in Enteric Glucose Sensing
Knauf, C., Cani, P. D., Kim, D., Iglesias, M. A., Chabo, C., Waget, A., Colom, A., Rastrelli, S., Delzenne, N. M., Drucker, D. J., et al. (2008) · Diabetes · doi:10.2337/db07-1788 · Cited by 123 · see citing works
“This would require the use of different sets of tracers not applicable to mouse infusion procedures, as discussed previously (4).”
MethodResultSelf-citationInteraction of the endocrine system with inflammation: a function of energy and volume regulation
Straub, R. H. (2014) · Arthritis Research & Therapy · doi:10.1186/ar4484 · Cited by 121 · see citing works
“In the feeding situation, vagal afferents together with gastrointestinal hormones such as cholecystokinin transmit signals to the dorsal vagal complex, leading to satiety signals, activation of the sympathetic nervous system (SNS) (short-lived post-prandial thermogenesis and hypermetabolism), activation of efferent va…”
Backgroundα-cell glucokinase suppresses glucose-regulated glucagon secretion
Basco, D., Zhang, Q., Salehi, A. A., Tarasov, A. I., Dolci, W., Herrera, P. L., Spiliotis, I., Berney, X. P., Tarussio, D., Rorsman, P., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03034-0 · Cited by 111 · see citing works
Self-citationGLP-1, the Gut-Brain, and Brain-Periphery Axes
Cabou, C., & Burcelin, R. (2011) · The Review of Diabetic Studies · doi:10.1900/rds.2011.8.418 · Cited by 110 · see citing works
“Initially, we showed that a low rate infusion of glucose into the portal vein caused a paradoxical hypoglycemia [65-66].”
BackgroundSelf-citationGLUT2 in pancreatic and extra-pancreatic gluco-detection
Thorens, B. (2001) · Molecular Membrane Biology · doi:10.1080/09687680110100995 · Cited by 110 · see citing works
“This corrected all the glucose metabolic abnormalities of GLUT27 /7 hepatocytes (Burcelin et al. 2000c).”
BackgroundInfluentialSelf-citationZderic, T. W., Davidson, C. J., Schenk, S., Byerley, L. O., & Coyle, E. F. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00159.2003 · Cited by 110 · see citing works
GLUT2 and the incretin receptors are involved in glucose-induced incretin secretion
Cani, P. D., Holst, J. J., Drucker, D. J., Delzenne, N. M., Thorens, B., Burcelin, R., & Knauf, C. (2007) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2007.06.003 · Cited by 106 · see citing works
Self-citationKnauf, C., Cani, P. D., Ait-Belgnaoui, A., Bénani, A., Dray, C., Cabou, C., Colom, A., Uldry, M., Rastrelli, S., Sabatier, E., et al. (2008) · Endocrinology · doi:10.1210/en.2008-0180 · Cited by 99 · see citing works
Self-citationGastric Bypass Reduces Symptoms and Hormonal Responses in Hypoglycemia
Abrahamsson, N., Lau, J., Sundbom, M., Wiklund, U., Karlsson, F. A., & Eriksson, J. W. (2016) · Diabetes · doi:10.2337/db16-0341 · Cited by 92 · see citing works
“Autonomic nerve activation contributes to hormonal responses and also directly influences glucose turnover in liver, muscle, and adipose tissue (11).”
BackgroundControl of hepatocyte metabolism by sympathetic and parasympathetic hepatic nerves
Püschel, G. P. (2004) · The Anatomical Record Part A Discoveries in Molecular Cellular and Evolutionary Biology · doi:10.1002/ar.a.20091 · Cited by 83 · see citing works
“Sensing of the portal-arterial gradient was dependent on Glut2 glucose transporter (Burcelin et al., 2000a) and GLP-1 receptor (probably in the portal sensing area) (Burcelin et al., 2001) as well as the Glut4 transporter and the AMP-kinase in skeletal muscle (Burcelin et al., 2003a).”
BackgroundGut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide
Candeias, E. (2015) · World Journal of Diabetes · doi:10.4239/wjd.v6.i6.807 · Cited by 83 · see citing works
Jager, J., Corcelle, V., Grémeaux, T., Laurent, K., Waget, A., Pagès, G., Binétruy, B., MARCHAND‐BRUSTEL, Y. L., Burcelin, R., Bost, F., et al. (2010) · Diabetologia · doi:10.1007/s00125-010-1944-0 · Cited by 82 · see citing works
“Hyperinsulinaemic–euglycaemic clamp studies These experiments were performed on 12-week-old animals as described by Burcelin et al. [ 22 , 23].”
MethodSelf-citationGLP-1 Effects on Islets: Hormonal, Neuronal, or Paracrine?
Donath, M., & Burcelin, R. (2013) · Diabetes Care · doi:10.2337/dcs13-2015 · Cited by 76 · see citing works
“(9-36)amide by dipeptidyl peptidase IV in”
Self-citationGlucose sensing and the pathogenesis of obesity and type 2 diabetes
Thorens, B. (2008) · International Journal of Obesity · doi:10.1038/ijo.2008.208 · Cited by 78 · see citing works
Self-citationIonut, V., Hücking, K., Liberty, I. F., & Bergman, R. N. (2005) · Diabetologia · doi:10.1007/s00125-005-1709-3 · Cited by 77 · see citing works
“Recent work suggesting that GLP-1 can modulate the activity of the hepatoportal sensor in mice [20] has not been confirmed in other studies [21].”
ResultEvidence That Extrapancreatic GLUT2-Dependent Glucose Sensors Control Glucagon Secretion
Burcelin, R., & Thorens, B. (2001) · Diabetes · doi:10.2337/diabetes.50.6.1282 · Cited by 73 · see citing works
“In addition to central glucose detection units, other peripheral glucose sensors, such as those present in the hepatoportal vein, which we recently showed to be GLUT2dependent (46,47), may also be involved in controlling ANS activity.”
BackgroundSelf-citationRegulation of hepatic and peripheral glucose disposal
Moore, M. C., Cherrington, A. D., & Wasserman, D. H. (2003) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/s1521-690x(03)00036-8 · Cited by 74 · see citing works
Gut-derived signaling molecules and vagal afferents in the control of glucose and energy homeostasis
Thorens, B., & Larsen, P. J. (2004) · Current Opinion in Clinical Nutrition and Metabolic Care · doi:10.1097/01.mco.0000134368.91900.84 · Cited by 73 · see citing works
Self-citationKnauf, C., Rieusset, J., Foretz, M., Cani, P. D., Uldry, M., Hosokawa, M., Martinez, E., Bringart, M., Waget, A., Kersten, S., et al. (2006) · Endocrinology · doi:10.1210/en.2005-1536 · Cited by 72 · see citing works
Self-citationThe incretins: a link between nutrients and well-being
Burcelin, R. (2005) · British Journal Of Nutrition · doi:10.1079/bjn20041340 · Cited by 71 · see citing works
“4) and utilization in a subset of tissues, mostly heart, soleus and brown adipose tissue (Burcelin et al. 2000 b ).”
Self-citationDietary fat sensing via fatty acid oxidation in enterocytes: possible role in the control of eating
Langhans, W., Leitner, C., & Arnold, M. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00610.2010 · Cited by 69 · see citing works
“The available evidence from behavioral, anatomical, and electrophysiological studies now indicates that vagal afferents terminating in the wall of the hepatic portal vein (HPV) function as sensors for absorbed glucose generating signals that can influence eating (155, 157), insulin release (7, 120), and, hence, glucos…”
BackgroundImai, J., & Katagiri, H. (2021) · International Immunology · doi:10.1093/intimm/dxab023 · Cited by 63 · see citing works
Mechanisms Underlying Type 2 Diabetes Remission After Metabolic Surgery
Pérez‐Pevida, B., Escalada, J., Miras, A. D., & Frühbeck, G. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00641 · Cited by 67 · see citing works
Wu, D., Yang, M., Chen, Y., Jia, Y., Ma, Z. A., Boden, G. H., Li, L., & Yang, G. (2014) · Diabetes · doi:10.2337/db13-0899 · Cited by 66 · see citing works
Nielsen, L. B., Ploug, K. B., Swift, P. G. F., Ørskov, C., Jansen‐Olesen, I., Chiarelli, F., Holst, J. J., Hougaard, P., Pörksen, S., Holl, R. W., et al. (2007) · European Journal of Endocrinology · doi:10.1530/eje-06-0756 · Cited by 60 · see citing works
Burcelin, R., Crivelli, V., Perrin, C., Costa, A. D., Mu, J., Kahn, B. B., Birnbaum, M. J., Kahn, C. R., Vollenweider, P., & Thorens, B. (2003) · Journal of Clinical Investigation · doi:10.1172/jci16888 · Cited by 69 · see citing works
“3 M) precipitation or a perchloric acid solution (6%) (8).”
BackgroundMethodResultInfluentialSelf-citationDelaere, F., Magnan, C., & Mithieux, G. (2010) · Diabetes & Metabolism · doi:10.1016/j.diabet.2010.05.001 · Cited by 57 · see citing works
Cruciani‐Guglielmacci, C., Vincent-Lamon, M., Rouch, C., Orosco, M., Ktorza, A., & Magnan, C. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00225.2004 · Cited by 57 · see citing works
Burcelin, R., Crivelli, V., Perrin, C., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200316888 · Cited by 57 · see citing works
Self-citationGlucosensing in the gastrointestinal tract: Impact on glucose metabolism
Fournel, A., Marlin, A., Abot, A., Pasquio, C., Cirillo, C., Cani, P. D., & Knauf, C. (2016) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00015.2016 · Cited by 56 · see citing works
“Therefore, central GLP-1 is linked to the regulation of the ANS.”
InfluentialTime-dependent growth of zinc hydroxide nanostrands and their crystal structure
Peng, X., Jin, J., Kobayashi, N., et al. (2008) · Chemical Communications · doi:10.1039/b719497h · Cited by 56 · see citing works
Glucagon-Like Peptide-1 and Energy Homeostasis3
Burcelin, R., Cani, P. D., & Knauf, C. (2007) · Journal of Nutrition · doi:10.1093/jn/137.11.2534s · Cited by 55 · see citing works
Self-citationChen, M., Feng, H., Gupta, D., Kelleher, J. D., Dickerson, K. E., Wang, J., Hunt, D. G., Jou, W., Gavrilova, O., Jin, J., et al. (2009) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00443.2008 · Cited by 55 · see citing works
Gautier‐Stein, A., Zitoun, C., Lalli, E., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603258200 · Cited by 50 · see citing works
Portal glucose influences the sensory, cortical and reward systems in rats
Delaere, F., Akaoka, H., Vadder, F. D., Duchampt, A., & Mithieux, G. (2013) · European Journal of Neuroscience · doi:10.1111/ejn.12354 · Cited by 50 · see citing works
“…stimulus for the acquisition of learned food preference (Tordoff & Friedman, 1986); (iii) induces insulin secretion (Fukaya et al., 2007) and glucose uptake (Burcelin et al., 2000; Moore et al., 2000) and (iv) inhibits the sympathoadrenal response to slow-onset hypoglycaemia (Saberi et al., 2008).”
BackgroundA role for the gut-to-brain GLP-1-dependent axis in the control of metabolism
Burcelin, R., Sérino, M., & Cabou, C. (2009) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2009.09.003 · Cited by 47 · see citing works
Self-citationJohnson, K., Edgerton, D. S., Rodewald, T., Scott, M. F., Farmer, B., Neal, D. W., & Cherrington, A. D. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00275.2007 · Cited by 46 · see citing works
Merino, B., Fernández-Díaz, C. M., Parrado‐Fernández, C., González-Casimiro, C. M., Postigo, T., Lobatón, C. D., Leissring, M. A., Cózar‐Castellano, I., & Perdomo, G. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154352 · Cited by 46 · see citing works
“Following intestinal glucose absorption, GLUT2 acts as a glucose-sensor inducing a nervous signal that stimulates first-phase insulin secretion [41,42].”
BackgroundYamada, T., Oka, Y., & Katagiri, H. (2007) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2007.09.006 · Cited by 45 · see citing works
Dialogue between muscle and fat
Birnbaum, M. J. (2001) · Nature · doi:10.1038/35055643 · Cited by 45 · see citing works
Hayes, M. T., Foo, J., Besic, V., et al. (2011) · Obesity Surgery · doi:10.1007/s11695-011-0380-7 · Cited by 42 · see citing works
What can bariatric surgery teach us about the pathophysiology of type 2 diabetes?
Andréelli, F., Amouyal, C., Magnan, C., & Mithieux, G. (2009) · Diabetes & Metabolism · doi:10.1016/s1262-3636(09)73456-1 · Cited by 40 · see citing works
The gut-brain axis: a major glucoregulatory player
Burcelin, R. (2010) · Diabetes & Metabolism · doi:10.1016/s1262-3636(10)70468-7 · Cited by 37 · see citing works
Self-citationCentral control of glucose homeostasis: the brain – endocrine pancreas axis
Thorens, B. (2010) · Diabetes & Metabolism · doi:10.1016/s1262-3636(10)70466-3 · Cited by 38 · see citing works
Self-citationA gene knockout approach in mice to identify glucose sensors controlling glucose homeostasis
Thorens, B. (2003) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-002-0954-2 · Cited by 35 · see citing works
“Reprinted with permission from [62] and [63] 487”
BackgroundSelf-citationNeuronal glucose sensing mechanisms and circuits in the control of insulin and glucagon secretion.
Thorens, B. (2024) · Physiological Reviews · doi:10.1152/physrev.00038.2023 · Cited by 31 · see citing works
“When glucose is infused in the portal vein at a relatively high rate, corresponding to endogenous glucose production, it triggers glucose uptake in muscle, heart, and brown fat by an insulin-in-dependent mechanism (137 – 139).”
BackgroundSelf-citationForegut exclusion disrupts intestinal glucose sensing and alters portal nutrient and hormonal milieu
Pal, A., Rhoads, D. B., & Tavakkoli, A. (2015) · Diabetes · doi:10.2337/db14-1578 · Cited by 29 · see citing works
“In addition to the foregut, evidence is emerging for a sensory function of the portal vein (8,9).”
BackgroundThe AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity
Viollet, B., Andréelli, F., Jørgensen, S. B., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200316567 · Cited by 29 · see citing works
Self-citationMechanisms for the cardiovascular effects of glucagon-like peptide-1
Poudyal, H. (2015) · Acta Physiologica · doi:10.1111/apha.12604 · Cited by 28 · see citing works
“Portal glucose infusion in GLUT2 knockout mice did not induce the hypoglycaemia and re-expression of GLUT2 in hepatocytes did not restore the development of hypoglycaemia after initiating portal vein glucose infusion (Burcelin et al. 2000a).”
BackgroundInfluentialMoore, M. C., Cardin, S., Edgerton, D. S., Farmer, B., Neal, D. W., Lautz, M., & Cherrington, A. D. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00343.2003 · Cited by 28 · see citing works
“Interestingly, the only skeletal muscle that Burcelin et al (7) observed to exhibit a substantial enhancement of glucose uptake following portal glucose infusion was soleus (composed primarily of oxidative fibers), suggesting that 5-HT is involved in the extrahepatic effects of the portal signal.”
BackgroundResultInfluentialThe role of hepatic portal glucose sensing in modulating responses to hypoglycaemia in man
Smith, D., Pernet, A., Reid, H., Bingham, E., Rosenthal, J., Macdonald, I. A., Umpleby, A. M., & Amiel, S. A. (2002) · Diabetologia · doi:10.1007/s00125-002-0909-3 · Cited by 27 · see citing works
“Portal-arterial glucose gradients have been implicated in the control of net hepatic glucose uptake [38, 39, 40], food intake [41], and recently tissue glucose utilisation [42].”
BackgroundGLP-1-Based Strategies: A Physiological Analysis of Differential Mode of Action
Burcelin, R., Gourdy, P., & Dalle, S. (2014) · Physiology · doi:10.1152/physiol.00009.2013 · Cited by 26 · see citing works
Self-citationVella, A. V., Shah, P., Basu, R., Basu, A., Camilleri, M., Schwenk, W. F., & Rizza, R. A. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00178.2001 · Cited by 26 · see citing works
Amouyal, C., & Andréelli, F. (2016) · Journal of Diabetes Research · doi:10.1155/2016/5908656 · Cited by 25 · see citing works
Carmean, C. M., Bobe, A. M., Yu, J. C., Volden, P. A., & Brady, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067807 · Cited by 23 · see citing works
Regulation of hepatic metabolism by enteral delivery of nutrients
Dardevet, D. P., Moore, M. C., Rémond, D., Grueter, C. A., & Cherrington, A. D. (2006) · Nutrition Research Reviews · doi:10.1017/s0954422407315175 · Cited by 24 · see citing works
Joubert, M., Metayer, L., Prévost, G., et al. (2014) · Acta Diabetologica · doi:10.1007/s00592-014-0636-5 · Cited by 24 · see citing works
Mechanism of rapid-phase insulin response to elevation of portal glucose concentration
Fukaya, M., Mizuno, A., Arai, H., Muto, K., Uebanso, T., Matsuo, K., Yamamoto, H., Taketani, Y., Doi, T., & Takeda, E. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00536.2006 · Cited by 24 · see citing works
Metabolic response to high-carbohydrate and low-carbohydrate meals in a nonhuman primate model
Fabbrini, E., Higgins, P. B., Magkos, F., Bastarrachea, R. A., Voruganti, V. S., Comuzzie, A. G., Shade, R. E., Gastaldelli, A., Horton, J. D., Omodei, D., et al. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00347.2012 · Cited by 22 · see citing works
García-Luna, C., Sanchez‐Watts, G., Arnold, M., de Lartigue, G., DeWalt, N., Langhans, W., & Watts, A. G. (2021) · eNeuro · doi:10.1523/eneuro.0419-20.2021 · Cited by 20 · see citing works
“…exocrine (Love et al., 2007) and endocrine function (Buijs et al., 2001; Taborsky and Mundinger, 2012), particularly insulin secretion (Ahrén and Taborsky, 1986; Nagase et al., 1993), a mechanism that may contribute to the hypoglycemic response to HPV hyperglycemia (Burcelin et al., 2000).”
Mithieux, G. (2010) · Diabetes & Metabolism · doi:10.1016/s1262-3636(10)70467-5 · Cited by 19 · see citing works
Cura, A. J., & Carruthers, A. (2012) · Comprehensive physiology · doi:10.1002/j.2040-4603.2012.tb00424.x · Cited by 19 · see citing works
Johnson, K., Edgerton, D. S., Rodewald, T., Scott, M. F., Farmer, B., Neal, D. W., & Cherrington, A. D. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00642.2007 · Cited by 18 · see citing works
Malbert, C.-H., Chauvin, A., Horowitz, M., & Jones, K. L. (2021) · Diabetes · doi:10.2337/db20-0361 · Cited by 18 · see citing works
Brain Processing of Duodenal and Portal Glucose Sensing
Boubaker-Vitre, J., Val‐Laillet, D., Guérin, S., & Malbert, C. (2012) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2012.02326.x · Cited by 18 · see citing works
Gautier‐Stein, A., Zitoun, C., Lalli, E., et al. (2006) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)84039-5 · Cited by 18 · see citing works
Comparison of intraduodenal and intravenous glucose metabolism under clamp conditions in humans
Féry, F., Tappy, L., Deviere, J. M. E., et al. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00201.2003 · Cited by 18 · see citing works
Distinct Classes of Central GLUT2-Dependent Sensors Control Counterregulation and Feeding
Marty, N., Bady, I., & Thorens, B. (2006) · Diabetes · doi:10.2337/db06-s014 · Cited by 17 · see citing works
“We have provided evidence that this sensor, activated by intraportal glucose infusion in conscious mice, increases the rate of glucose clearance by a subset of peripheral tissues: brown fat, soleus muscle, and the heart (8).”
BackgroundSelf-citationHepatic interoception in health and disease
Berthoud, H., Münzberg, H., Morrison, C. D., & Neuhuber, W. (2024) · Autonomic Neuroscience · doi:10.1016/j.autneu.2024.103174 · Cited by 17 · see citing works
“…insulin, is critical for regulation of postprandial hepatic glucose uptake and the overall allocation of glucose to other organs (Adkins-Marshall et al., 1992; Burcelin et al., 2000; Cherrington et al., 1987; Galassetti et al., 1998; Stumpel and Jungermann, 1997), reviewed by (Moore et al., 2012).”
InfluentialImpact of PPAR-α induction on glucose homoeostasis in alcohol-fed mice
Lebrun, V., Molendi‐Coste, O., Lanthier, N., Sempoux, C. L., Cani, P. D., van Rooijen, N., Stärkel, P., Horsmans, Y., & Leclercq, I. A. (2013) · Clinical Science · doi:10.1042/cs20130064 · Cited by 15 · see citing works
Effect of Portal Glucose Sensing on Systemic Glucose Levels in SD and ZDF Rats
Pal, A., Rhoads, D. B., & Tavakkoli, A. (2016) · PLoS ONE · doi:10.1371/journal.pone.0165592 · Cited by 14 · see citing works
Charpentier, J., Waget, A., Klopp, P., Magnan, C., Cruciani‐Guglielmacci, C., Lee, S. J., Burcelin, R., & Grasset, E. (2018) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00348.2017 · Cited by 15 · see citing works
“lixisenatide has been described as des-38-proline-exendin-4(1-39)-peptidylpenta-L-lysyl-L-lysinamide, which is derived from the first 39 amino acids of exendin 4 omitting proline at position 38 and adding six lysine residues (11).”
BackgroundSelf-citationGrasset, E., Puel, A., Charpentier, J., Klopp, P., Christensen, J. E., Lelouvier, B., Servant, F., Blasco‐Baqué, V., Tercé, F., & Burcelin, R. (2021) · Acta Diabetologica · doi:10.1007/s00592-021-01790-y · Cited by 14 · see citing works
Self-citationMithieux, G. (2012) · Current Diabetes Reports · doi:10.1007/s11892-012-0257-8 · Cited by 13 · see citing works
Ertl, A. C., Mann, S. L., Richardson, A., Briscoe, V. J., Blair, H. B., Tate, D. B., & Davis, S. N. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90470.2008 · Cited by 11 · see citing works
Impact of portal glucose delivery on glucose metabolism in conscious, unrestrained mice
Chueh, F., Malabanan, C. M., & McGuinness, O. P. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00608.2005 · Cited by 11 · see citing works
Zangeneh, F., Basu, R., Shah, P., et al. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00055.2003 · Cited by 11 · see citing works
The Hepatoportal Glucose Sensor
Thorens, B. (2004) · KARGER eBooks · doi:10.1159/000079027 · Cited by 10 · see citing works
Self-citationThe contribution of afferent signals from the liver to metabolic regulation during exercise
Lavoie, J.-M. (2002) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y02-137 · Cited by 10 · see citing works
Zheng, D., Ionut, V., Mooradian, V., Stefanovski, D., & Bergman, R. N. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00280.2009 · Cited by 9 · see citing works
- Authors
- Burcelin, R., Dolci, W., & Thorens, B.
- Affiliations
- University of Lausanne (CH)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2000-10-01
- Volume
- 49
- Issue
- 10
- Pages
- 1635-1642
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2137028096
- Cited by
- 137
- References
- 0
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 6 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 5 · 2015: 6 · 2014: 6 · 2013: 11 · 2012: 6
- FWCI
- 7.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- hypoglycemia, glucose infusion, portal vein, somatostatin, insulin, insulin-independent glucose uptake, heart, brown adipose tissue, soleus muscle, glucose clearance, 2-deoxyglucose, glucose metabolism
- MeSH terms
- Animals, Blood Glucose, Glucose, Homeostasis, Hypoglycemia, Hypothalamus, Infusions, Intravenous, Insulin, Liver, Metabolic Clearance Rate, Mice, Inbred C57BL, Muscle Denervation, Portal Vein, Somatostatin, Vagus Nerve, Muscle, Skeletal, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
