Free fatty acids increase insulin secretion and modulates expression of genes involved in insulin biosynthesis in islets from malnourished rats / Acido graxo aumenta a secreção de insulina e modula a expressão de genes envolvidos na biossintese de insulina em ilhotas de ratos submetidos a desnutrição proteica

AUTOR(ES)

Vanessa Cristina Arantes

DATA DE PUBLICAÇÃO

2006

RESUMO

A severe reduction in insulin release in response to glucose is consistently noticed in protein-deprived rats and is attributed partly to the chronic exposure to elevated levels of free fatty acids. Since the pancreatic and duodenal transcription factor homeobox 1 (PDX-1) is important for the maintenance of B-cell physiology, and since PDX-1 expression is altered in the islets of rats fed a low protein diet, we assessed PDX-1 and insulin mRNA expression, as well as PDX-1 and p38/SAPK2 protein expression, in islets from young rats fed low (6%; LP) or normal (17%; C) protein diets and maintained for 48 h in culture medium containing 5.6 mmol glucose/L with or without 0.6 mmol palmitic acid/L. We also measured glucoseinduced insulin secretion and glucose metabolism. Insulin secretion by isolated islets in response to 16.7 mmol glucose/L was reduced in LP compared to C rats. In the presence of free fatty acids, there was an increase in insulin secretion in both groups At 2.8 mmol glucose/L, the metabolism of this sugar was reduced in LP islets, regardless of the presence of this fatty acid. However, when challenged with 16.7 mmol glucose/L, LP and C islets showed a severe reduction in glucose oxidation in the presence of free fatty acid. The PDX-1 and insulin mRNA were significantly higher when free fatty acid was added to the culture medium in both groups of islets.The effect of palmitic acid on PDX-1 and p38/SAPK2 protein levels was similar in LP and C islets, but the increase was much more evident in LP islets. These results demonstrate the complex interrelationship between nutrients in the control of insulin release and support the view that fatty acids play an important role in glucose homeostasis by affecting molecular mechanisms and stimulus/secretion coupling pathways

ASSUNTO(S)

malnutrition fatores de transcrição ilhotas de desnutrição langerhans transcription factors islands of langerhans

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