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

Author(s)

Leite, Nayara Carvalho ; de Paula, Flavia ; Borck, Patricia Cristine ; Vettorazzi, Jean Franciesco ; Souto Branco, Renato Chaves ; Lubaczeuski, Camila ; Boschero, Antonio Carlos ; Zoppi, Claudio Cesar ; Carneiro, Everardo Magalhaes

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 6, SEP 16 2016.
• Web of Science Citations: 6

Abstract

Pancreatic beta cell (beta) dysfunction is an outcome of malnutrition. We assessed the role of the amplifying pathway (AMP PATH) in beta 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 beta cells, leading to an increased contribution of the AMP PATH to insulin secretion through the enhancement of GDH content and activity. (AU)

• FAPESP's process: 11/19536-2 - Metabolic control of insulin secretion in islets of Langerhans from mice submitted to experimental protein malnourishment and obesity
• Grantee: Everardo Magalhães Carneiro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center
• Grantee: Licio Augusto Velloso
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 11/09012-6 - Molecular mechanisms involved in the dysfunction and death of pancreatic beta cells in Diabetes Mellitus: strategies for the prevention of islet dysfunction and for islet mass recuperation in different cellular and animal models
• Grantee: Antonio Carlos Boschiero
• Support Opportunities: Research Projects - Thematic Grants