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Glucose Metabolism In Vivo in Four Commonly Used Inbred Mouse Strains Eric D. Berglund 1 , Candice Y. Li 1 2 , Greg Poffenberger 3 , Julio E. Ayala 1 2 , Patrick T. Fueger 4 , Shannon E. Willis 3 , Marybeth M. Jewell 3 , Alvin C. Powers 1 3 5 and David H. Wasserman 1 2 1 Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 2 Vanderbilt University–NIH Mouse Metabolic Phenotyping Center, Vanderbilt University School of Medicine, Nashville, Tennessee 3 Department of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University School of Medicine, Nashville, Tennessee 4 Departments of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 5 VA Tennessee Valley Healthcare System, Nashville, Tennessee Corresponding author: Eric Berglund, eric.d.berglund{at}vanderbilt.edu Abstract OBJECTIVE —To characterize differences in whole-body glucose metabolism between commonly used inbred mouse strains. RESEARCH DESIGN AND METHODS —Hyperinsulinemic-euglycemic (∼8.5 mmol/l) and -hypoglycemic (∼3.0 mmol/l) clamps were done in catheterized, 5-h-fasted mice to assess insulin action and hypoglycemic counter-regulatory responsiveness. Hyperglycemic clamps (∼15 mmol/l) were done to assess insulin secretion and compared with results in perifused islets. RESULTS —Insulin action and 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 among 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 that in 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. Footnotes Published ahead of print at http://diabetes.diabetesjournals.org on 8 April 2008. Readers may use this article as long as the work is properly cited, the use is educational and not for profit,and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted April 3, 2008. Received November 15, 2007. DIABETES