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.
Intrauterine growth restriction is associated with chronically elevated levels of serum fatty acids and reduced glucose-stimulated insulin secretion. Lipid metabolism in pancreatic beta 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.
de Barros Reis
Marise Auxiliadora
MA
Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas, 13083970 Campinas, SP, Brazil. marise_reis@cpd.ufmt.br
Arantes
Vanessa Cristina
VC
Cunha
Daniel Andrade
DA
Latorraca
Márcia Queiroz
MQ
Toyama
Marcos Hikari
MH
Carneiro
Everardo Magalhães
EM
Boschero
Antonio Carlos
AC
D000818:Animals; D001483:Base Sequence; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D015870:Gene Expression; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000201:enzymology*; D008099:Liver / Q000201:enzymology; D008297:Male; D044342:Malnutrition / Q000201:enzymology*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D017931:DNA Primers; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D002334:Carnitine O-Palmitoyltransferase; D005947:Glucose