The Amplifying Pathway of the ?-Cell Contributes to Diet-induced Obesity.

ABSTRACT: Efficient energy storage in adipose tissues requires optimal function of the insulin-producing ?-cell, whereas its dysfunction promotes diabetes. The associated paradox related to ?-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 ?-cell-selective glutamate dehydrogenase deletion (?Glud1(-/-)), lacking an amplifying pathway of insulin secretion. As opposed to control mice, ?Glud1(-/-) animals fed a high calorie diet maintained glucose tolerance and did not develop diet-induced obesity. Islets of ?Glud1(-/-) 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 ?Glud1(-/-) mice compared with controls, in particular during food intake periods. These results show that reduced ?-cell function prior to high calorie feeding prevented diet-induced obesity.

SUBMITTER: Vetterli L 

PROVIDER: S-EPMC4933223 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature