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Glucose metabolism in vivo in four commonly used inbred mouse strains

¹Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, 37232
²Vanderbilt University – NIH Mouse Metabolic Phenotyping Center, Vanderbilt University School of Medicine, Nashville, TN, 37232
³Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University School of Medicine, Nashville, TN, 37232
⁴Departments of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, 27044
⁵VA Tennessee Valley Healthcare System, Nashville, TN, 37232

Objective: Characterize differences in whole-body glucose metabolism between commonly used inbred mouse strains.

Research Design and Methods: Hyperinsulinemic-euglycemic (8.5 mmol•L^–1) and –hypoglycemic (3.0 mmol•L^–1) clamps were done in catheterized, 5h-fasted mice to assess insulin action and hypoglycemic counter-regulatory responsiveness. Hyperglycemic clamps (15 mmol•L^–1) were done to assess insulin secretion and compared to results in perifused islets.

Results: Insulin action, hypoglycemic counter-regulatory, and insulin secretory phenotypes varied considerably in four inbred mouse strains. In vivo insulin secretion was greatest in 129X1/Sv mice, but the counter-regulatory response to hypoglycemia was blunted. FVB/N mice in vivo showed no increase in glucose-stimulated insulin secretion, relative hepatic insulin resistance, and the highest counter-regulatory response to hypoglycemia. In DBA/2 mice, insulin action was lowest amongst the strains and islets isolated had the greatest glucose-stimulated insulin secretion in vitro. In C57BL/6 mice, in vivo physiological responses to hyperinsulinemia at euglycemia and hypoglycemia were intermediate relative to other strains. Insulin secretion by C57BL/6 mice was similar to other strains in contrast to the blunted glucose-stimulated insulin secretion from isolated islets.

Conclusions: Strain-dependent differences exist in four inbred mouse strains frequently used for genetic manipulation and study of glucose metabolism. These results are important for selecting inbred mice to study glucose metabolism and for interpreting and designing experiments.

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