Journal Article

Portal glucose infusion in the mouse induces hypoglycemia: evidence that the hepatoportal glucose sensor stimulates glucose utilization

W Dolci, B Thorens, R Burcelin

2000

Overview

Portal glucose infusion in the mouse induces hypoglycemia: evidence that the hepatoportal glucose sensor stimulates glucose utilization. R Burcelin , W Dolci and B Thorens Institute of Pharmacology, University of Lausanne, Switzerland. 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.

• Publisher: American Diabetes Association
• Subject: Animals / Biological and medical sciences / Blood Glucose - metabolism / Body fat / Carbohydrates / Diabetes / Fundamental and applied biological sciences. Psychology / Glucose / Glucose - administration & dosage / Glucose - metabolism / Homeostasis / Hypoglycemia / Hypoglycemia - chemically induced / Hypothalamus - physiology / Infusions, Intravenous / Insulin / Insulin - blood / Liver - innervation / Metabolic Clearance Rate / Metabolisms and neurohumoral controls / Mice / Mice, Inbred C57BL / Muscle Denervation / Muscle, Skeletal - innervation / Muscle, Skeletal - metabolism / Portal Vein - innervation / Sensors / Somatostatin - pharmacology / Vagus Nerve - physiology / Veins & arteries / Vertebrates: anatomy and physiology, studies on body, several organs or systems