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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.
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“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]
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GLUT2, glucose sensing and glucose homeostasis
Thorens, B. (2015) · Diabetologia · doi:10.1007/s00125-014-3451-1 · Cited by 722
“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
“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
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 361
“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 360
Metadata
- 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 › Endocrinology, Diabetes and Metabolism › 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
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