PPARalpha activation reverses adverse effects induced by high-saturated-fat feeding on pancreatic beta-cell function in late pregnancy

Autor: Nicholas D. Smith, Mark J. Holness, Mary C. Sugden, Gemma K. Greenwood
Rok vydání: 2006
Předmět:
Zdroj: American journal of physiology. Endocrinology and metabolism. 292(4)
ISSN: 0193-1849
Popis: We examined whether the additional demand for insulin secretion imposed by dietary saturated fat-induced insulin resistance during pregnancy is accommodated at late pregnancy, already characterized by insulin resistance. We also assessed whether effects of dietary saturated fat are influenced by PPARα activation or substitution of 7% of dietary fatty acids (FAs) with long-chain ω-3 FA, manipulations that improve insulin action in the nonpregnant state. Glucose tolerance at day 19 of pregnancy in the rat was impaired by high-saturated-fat feeding throughout pregnancy. Despite modestly enhanced glucose-stimulated insulin secretion (GSIS) in vivo, islet perifusions revealed an increased glucose threshold and decreased glucose responsiveness of GSIS in the saturated-fat-fed pregnant group. Thus, insulin resistance evoked by dietary saturated fat is partially countered by augmented insulin secretion, but compensation is compromised by impaired islet function. Substitution of 7% of saturated FA with long-chain ω-3 FA suppressed GSIS in vivo but did not modify the effect of saturated-fat feeding to impair GSIS by perifused islets. PPARα activation (24 h) rescued impaired islet function that was identified using perifused islets, but GSIS in vivo was suppressed such that glucose tolerance was not improved, suggesting modification of the feedback loop between insulin action and secretion.
Databáze: OpenAIRE