4 years ago

Effect of liraglutide on dietary lipid-induced insulin resistance in humans

Julie Kurtz, Karen D'Souza, Lizette Lopez, James Deer, Arline D. Salbe, Peter D. Reaven, Sherman M. Harman, Tracy Osredkar, Juraj Koska
Aims To test whether liraglutide suppresses postprandial elevations in lipids and thus protects against high saturated fatty acid (SFA) diet-induced insulin resistance. Methods In a randomized placebo-controlled crossover study, 32 participants with normal or mildly impaired glucose tolerance received liraglutide and placebo for 3 weeks each. Insulin suppression tests (IST) were conducted at baseline and after a 24-hour SFA-enriched diet after each treatment. Plasma glucose, insulin, triglycerides and non-esterified fatty acids (NEFA) were measured over the initial 8 hours (breakfast and lunch) on the SFA diet. A subset of participants underwent ex vivo measurements of insulin-mediated vasodilation of adipose tissue arterioles and glucose metabolism regulatory proteins in skeletal muscle. Results Liraglutide reduced plasma glucose, triglycerides and NEFA concentrations during the SFA diet (by 50%, 25% and 9%, respectively), and the SFA diet increased plasma glucose during the IST (by 36%; all P < .01 vs placebo). The SFA diet-induced impairment of vasodilation on placebo (−9.4% vs baseline; P < .01) was ameliorated by liraglutide (−4.8%; P = .1 vs baseline). In skeletal muscle, liraglutide abolished the SFA-induced increase in thioredoxin-interacting protein (TxNIP) expression (75% decrease; P < .01 vs placebo) and increased 5′AMP-activated protein kinase (AMPK) phosphorylation (50% vs −3%; P = .04 vs placebo). Conclusions Liraglutide blunted the SFA-enriched diet-induced peripheral insulin resistance. This effect may be related to improved microvascular function and modulation of TxNIP and AMPK pathways in skeletal muscle.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/dom.13037

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