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Journal of Endocrinology (2005) 187, 45-53    DOI: 10.1677/joe.1.06333
© 2005 Society for Endocrinology

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Differential effect of inbred mouse strain (C57BL/6, DBA/2, 129T2) on insulin secretory function in response to a high fat diet

Sofianos Andrikopoulos, Christine M Massa, Kathryn Aston-Mourney, Alexandra Funkat, Barbara C Fam, Rebecca L Hull1, Steven E Kahn1 and Joseph Proietto

University of Melbourne, Department of Medicine (AH/NH), Heidelberg Repatriation Hospital, Heidelberg Heights, Victoria 3081, Australia
1 Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, Washington 98108, USA

(Requests for offprints should be addressed to S Andrikopoulos, University of Melbourne, Department of Medicine (AH/NH), Heidelberg Repatriation Hospital, 300 Waterdale Road, Heidelberg Heights, Victoria 3081, Australia; Email: sof{at}unimelb.edu.au)

The increasing production of genetically-modified mouse models has necessitated studies to determine the inherent physiological characteristics of commonly used mouse strains. In this study we examined insulin secretory function in response to an intravenous bolus of glucose or glucose plus arginine in anesthetized C57BL/6, DBA/2 and 129T2 mice fed either a control or high fat diet for 6 weeks. The results show that 129T2 mice had higher fasting plasma glucose levels and lower fasting plasma insulin levels compared with C57BL/6 and DBA/2 mice regardless of diet. Furthermore, 129T2 mice were glucose intolerant and secreted significantly less insulin in response to glucose and glucose plus arginine irrespective of diet compared with the other two strains of mice. DBA/2 mice hypersecreted insulin in response to glucose and glucose plus arginine compared with C57BL/6 and 129T2 mice. Moreover while first phase insulin secretion was appropriately increased in response to the high fat diet in C57BL/6 and 129T2 mice, this was not the case for DBA/2 mice. Mean islet area was decreased in response to a high fat diet in DBA/2 mice, while there was no dietary effect on the other two strains. This study highlights the inherent genetic differences that exist among seemingly normal strains of mice that are commonly used to make transgenic and knockout mice. Understanding these differences will provide researchers with the information to choose the appropriate genetic background on which to express their particular genetic alteration.




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