PPARalpha activation reverses adverse effects induced by high-saturated-fat feeding on pancreatic beta-cell function in late pregnancy.
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 PPARalpha activation or substitution of 7% of dietary fatty acids (FAs) with long-chain omega-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 omega-3 FA suppressed GSIS in vivo but did not modify the effect of saturated-fat feeding to impair GSIS by perifused islets. PPARalpha 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.
Holness
Mark J
MJ
Centre for Diabetes and Metabolic Medicine, Institute of Cell and Molecular Science, St.Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Smith
Nicholas D
ND
Greenwood
Gemma K
GK
Sugden
Mary C
MC
D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage*; D019587:Dietary Supplements; D005227:Fatty Acids / Q000008:administration & dosage / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000494:pharmacology; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D047493:PPAR alpha / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D004041:Dietary Fats; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D007328:Insulin; D047493:PPAR alpha; D005947:Glucose