Pancreatic islet adaptation to fasting is dependent on peroxisome proliferator-activated receptor α transcriptional up-regulation of fatty acid oxidation

S Gremlich, C Nolan, R Roduit, R Burcelin… - …, 2005 - academic.oup.com
S Gremlich, C Nolan, R Roduit, R Burcelin, ML Peyot, V Delghingaro-Augusto, B Desvergne
Endocrinology, 2005academic.oup.com
The cellular response to fasting and starvation in tissues such as heart, skeletal muscle, and
liver requires peroxisome proliferator-activated receptor-α (PPARα)-dependent up-
regulation of energy metabolism toward fatty acid oxidation (FAO). PPARα null (PPARαKO)
mice develop hyperinsulinemic hypoglycemia in the fasting state, and we previously showed
that PPARα expression is increased in islets at low glucose. On this basis, we hypothesized
that enhanced PPARα expression and FAO, via depletion of lipid-signaling molecule (s) for …
The cellular response to fasting and starvation in tissues such as heart, skeletal muscle, and liver requires peroxisome proliferator-activated receptor-α (PPARα)-dependent up-regulation of energy metabolism toward fatty acid oxidation (FAO). PPARα null (PPARαKO) mice develop hyperinsulinemic hypoglycemia in the fasting state, and we previously showed that PPARα expression is increased in islets at low glucose. On this basis, we hypothesized that enhanced PPARα expression and FAO, via depletion of lipid-signaling molecule(s) for insulin exocytosis, are also involved in the normal adaptive response of the islet to fasting. Fasted PPARαKO mice compared with wild-type mice had supranormal ip glucose tolerance due to increased plasma insulin levels. Isolated islets from the PPARα null mice had a 44% reduction in FAO, normal glucose use and oxidation, and enhanced glucose-induced insulin secretion. In normal rats, fasting for 24 h increased islet PPARα, carnitine palmitoyltransferase 1, and uncoupling protein-2 mRNA expression by 60%, 62%, and 82%, respectively. The data are consistent with the view that PPARα, via transcriptionally up-regulating islet FAO, can reduce insulin secretion, and that this mechanism is involved in the normal physiological response of the pancreatic islet to fasting such that hypoglycemia is avoided.
Oxford University Press