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Title: High fat feeding unmasks variable insulin responses in male C57BL/6 mouse substrains.
Austin Authors: Hull, Rebecca L;Willard, Joshua R;Struck, Matthias D;Barrow, Breanne M;Brar, Gurkirat S;Andrikopoulos, Sofianos;Zraika, Sakeneh
Affiliation: Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA
Division of Metabolism Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, Washington, USA
Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Issue Date: Apr-2017
Date: 2017-01-30
Publication information: The Journal of Endocrinology 2017; 233(1): 53-64
Abstract: Mouse models are widely used for elucidating mechanisms underlying type 2 diabetes. Genetic background profoundly affects metabolic phenotype; therefore, selecting the appropriate model is critical. Although variability in metabolic responses between mouse strains is now well recognized, it also occurs within C57BL/6 mice, of which several substrains exist. This within-strain variability is poorly understood and could emanate from genetic and/or environmental differences. To better define the within-strain variability, we performed the first comprehensive comparison of insulin secretion from C57BL/6 substrains 6J, 6JWehi, 6NJ, 6NHsd, 6NTac and 6NCrl. In vitro, glucose-stimulated insulin secretion correlated with Nnt mutation status, wherein responses were uniformly lower in islets from C57BL/6J vs C57BL/6N mice. In contrast, in vivo insulin responses after 18 weeks of low fat feeding showed no differences among any of the six substrains. When challenged with a high-fat diet for 18 weeks, C57BL/6J substrains responded with a similar increase in insulin release. However, variability was evident among C57BL/6N substrains. Strikingly, 6NJ mice showed no increase in insulin release after high fat feeding, contributing to the ensuing hyperglycemia. The variability in insulin responses among high-fat-fed C57BL/6N mice could not be explained by differences in insulin sensitivity, body weight, food intake or beta-cell area. Rather, as yet unidentified genetic and/or environmental factor(s) are likely contributors. Together, our findings emphasize that caution should be exercised in extrapolating data from in vitro studies to the in vivo situation and inform on selecting the appropriate C57BL/6 substrain for metabolic studies.
DOI: 10.1530/JOE-16-0377
ORCID: 0000-0002-8932-8592
Journal: The Journal of Endocrinology
PubMed URL: 28138002
Type: Journal Article
Subjects: C57BL/6 substrains
high-fat diet
insulin secretion
Appears in Collections:Journal articles

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