Increased L-CPT-1 activity and altered gene expression in pancreatic islets of malnourished adult rats: a possible relationship between elevated free fatty acid levels and impaired insulin secretion

• Published in: The Journal of nutritional biochemistry Vol. 19; no. 2; pp. 85 - 90
• Main Authors: de Barros Reis, Marise Auxiliadora, Arantes, Vanessa Cristina, Cunha, Daniel Andrade, Latorraca, Márcia Queiroz, Toyama, Marcos Hikari, Carneiro, Everardo Magalhães, Boschero, Antonio Carlos
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-02-2008; New York, NY: Elsevier Science; Elsevier Science
• Subjects: animal disease models; Animals; Base Sequence; Biological and medical sciences; blood lipids; Carnitine O-Palmitoyltransferase - genetics; Carnitine O-Palmitoyltransferase - metabolism; carnitine palmitoyltransferase; diet-related diseases; DNA Primers; Endocrine pancreas; enzyme activity; fatty acid oxidation; Fatty acids; Fatty Acids, Nonesterified - blood; Female; free fatty acids; Fundamental and applied biological sciences. Psychology; Gene Expression; gene overexpression; Genes; Glucose - pharmacology; Hormones. Régulation; hyperlipidemia; Insulin - metabolism; insulin resistance; Insulin Secretion; islets of Langerhans; Islets of Langerhans - enzymology; kwashiorkor; L-CPT-1; Liver - enzymology; long term effects; Low-protein diet; Male; Malnutrition; Malnutrition - enzymology; maternal nutrition; messenger RNA; mitochondria; nutrition-genotype interaction; ontogeny; pancreatic islet ontogeny; Polymerase Chain Reaction; postpartum period; Pregnancy; prenatal care; Rats; Rats, Wistar; Vertebrates: endocrinology; Low-protein diet; L-CPT-1; Malnutrition; Fatty acids; Genes; Insulin secretion; Animal model; Pancreatic hormone; Molecular form; Deficient diet; Rat; Liver; Lipids; Free fatty acid; Carnitine O-palmitoyltransferase; Endocrine secretion; Endocrine pancreas; Acyltransferases; Digestive system; Enzyme; Transferases; Rodentia; Nutrition disorder; Langerhans islet; Gene expression; Metabolism; Insulin; Protein; Feeding; Vertebrata; Mammalia; Adult animal; Hormonal regulation
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2007.01.005

Intrauterine growth restriction is associated with chronically elevated levels of serum fatty acids and reduced glucose-stimulated insulin secretion. Lipid metabolism in pancreatic β cells is critical for the regulation of insulin secretion, and the chronic exposure to fatty acids results in higher palmitate oxidation rates and an altered insulin response to glucose. Using a rat model of isocaloric protein restriction, we examined whether pre- and postnatal protein malnutrition influences the properties of pancreatic islet carnitine palmitoyltransferase-1 (liver isoform, L-CPT-1), a rate-limiting enzyme that regulates fatty acid oxidation in mitochondria. The activity of L-CPT-1 in pancreatic islets increased in the low protein (LP), although the L-CPT-1 mRNA levels were unaffected by malnutrition. The susceptibility of enzyme to inhibition by malonyl-CoA was unaltered and the content of malonyl-CoA was reduced in LP cells. Because the mitochondrial oxidation of fatty acids is related to the altered expression of a number of genes encoding proteins involved in insulin secretion, the levels of expression of insulin and GLUT-2 mRNA were assessed. A reduced expression of both genes was observed in malnourished rats. These results provide further evidence that increased L-CPT-1 activity and changes in gene expression in pancreatic islets may be involved in the reduced insulin secretion seen in malnourished rats.