Molecular and functional characterization of the K+ and Ca2+ channels involved in b-cell stimulus/secretion coupling in isolated islets from malnourished mice submitted to a high fat diet

Abstract

In insulin secretion, the K+ ATP (KATP) and Ca2+-voltage (Cav)-sensitive channels play an important role in the generation and maintenance of the action potential that contributes for beta-cell stimulus/secretion coupling. Several evidences show that decreased expression or activity of these channels result in lower beta-cell responsiveness. In this way, our laboratory has studied the mechanisms involved in metabolic responses in undernutrition and obesity, conditions that may account to type 2 diabetes development. We demonstrated that isolated islets from rodent submitted to a low protein diet (LP) showed decreased insulin secretion in response to glucose. This effect is followed by changes in the biphasic insulin secretory response to glucose where LP islets did not show first phase of secretion accompanied by a lower insulin release during the second phase. Decreased beta-cell function in LP islets was also observed in the presence of depolarizing agents and potentiators of the secretion. These effects are associated with a lower Ca2+ handling from the external and internal pools. However, isolated islets from high fat diet rodents showed hypersecretion to compensate the impaired insulin action. Therefore we hypothesize that the association between LP and high fat diet may lead to severe changes in endocrine pancreatic function such as decreased activity and expression of ion channels that are involved in the coupling between stimulus/excitability in beta-cell. The aim of this study is to perform a molecular and morphological characterization of the KATP and Cav channels in islets from LP mice fed a high fat diet. (AU)