Efficient energy storage in adipose tissues requires optimal function of the insulin-producing β-cell, whereas its dysfunction promotes diabetes. The associated paradox related to β-cell efficiency is that excessive accumulation of fat in adipose tissue predisposes for type 2 diabetes. Insulin exocytosis is regulated by intracellular metabolic signal transduction, with glutamate dehydrogenase playing a key role in the amplification of the secretory response. Here, we used mice with β-cell-selective glutamate dehydrogenase deletion (βGlud1(-/-)), lacking an amplifying pathway of insulin secretion. As opposed to control mice, βGlud1(-/-) animals fed a high calorie diet maintained glucose tolerance and did not develop diet-induced obesity. Islets of βGlud1(-/-) mice did not increase their secretory response upon high calorie feeding, as did islets of control mice. Inhibited adipose tissue expansion observed in knock-out mice correlated with lower expression of genes responsible for adipogenesis. Rather than being efficiently stored, lipids were consumed at a higher rate in βGlud1(-/-) mice compared with controls, in particular during food intake periods. These results show that reduced β-cell function prior to high calorie feeding prevented diet-induced obesity.
Keywords: beta cell (B-cell); insulin secretion; obesity; transgenic mice; type 2 diabetes.
© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.