| First Author | Vetterli L | Year | 2016 |
| Journal | J Biol Chem | Volume | 291 |
| Issue | 25 | Pages | 13063-75 |
| PubMed ID | 27137930 | Mgi Jnum | J:235012 |
| Mgi Id | MGI:5792619 | Doi | 10.1074/jbc.M115.707448 |
| Citation | Vetterli L, et al. (2016) The Amplifying Pathway of the beta-Cell Contributes to Diet-induced Obesity. J Biol Chem 291(25):13063-75 |
| abstractText | Efficient energy storage in adipose tissues requires optimal function of the insulin-producing beta-cell, whereas its dysfunction promotes diabetes. The associated paradox related to beta-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 beta-cell-selective glutamate dehydrogenase deletion (betaGlud1(-/-)), lacking an amplifying pathway of insulin secretion. As opposed to control mice, betaGlud1(-/-) animals fed a high calorie diet maintained glucose tolerance and did not develop diet-induced obesity. Islets of betaGlud1(-/-) 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 betaGlud1(-/-) mice compared with controls, in particular during food intake periods. These results show that reduced beta-cell function prior to high calorie feeding prevented diet-induced obesity. |
