Protein malnutrition potentiates the amplifying pathway of insulin secretion in adult obese mice

Nayara Carvalho Leite, Flávia De Paula, Patrícia Cristine Borck, Jean Franciesco Vettorazzi, Renato Chaves Souto Branco, Camila Lubaczeuski, Antonio Carlos Boschero, Claudio Cesar Zoppi, Everardo Magalhães Carneiro

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Pancreatic beta cell (β) dysfunction is an outcome of malnutrition. We assessed the role of the amplifying pathway (AMP PATH) in β cells in malnourished obese mice. C57Bl-6 mice were fed a control (C) or a low-protein diet (R). The groups were then fed a high-fat diet (CH and RH). AMP PATH contribution to insulin secretion was assessed upon incubating islets with diazoxide and KCl. CH and RH displayed increased glucose intolerance, insulin resistance and glucose-stimulated insulin secretion. Only RH showed a higher contribution of the AMP PATH. The mitochondrial membrane potential of RH was decreased, and ATP flux was unaltered. In RH islets, glutamate dehydrogenase (GDH) protein content and activity increased, and the AMP PATH contribution was reestablished when GDH was blunted. Thus, protein malnutrition induces mitochondrial dysfunction in β cells, leading to an increased contribution of the AMP PATH to insulin secretion through the enhancement of GDH content and activity.

Original languageEnglish (US)
Article number33464
JournalScientific reports
Volume6
DOIs
StatePublished - Sep 16 2016
Externally publishedYes

ASJC Scopus subject areas

  • General

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