Scientific article
Open access

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

Published inThe Journal of biological chemistry, vol. 291, no. 25, p. 13063-13075
Publication date2016

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.

  • diabetes
  • insulin
  • pancreatic islets
Citation (ISO format)
VETTERLI, Laurene Marine et al. The Amplifying Pathway of the β-Cell Contributes to Diet-induced Obesity. In: The Journal of biological chemistry, 2016, vol. 291, n° 25, p. 13063–13075. doi: 10.1074/jbc.M115.707448
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Article (Published version)
ISSN of the journal0021-9258

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