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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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Influential
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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