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

Juraj Koska, Lizette Lopez, Karen D'Souza, Tracy Osredkar, James Deer, Julie Kurtz, Arline D. Salbe, Sherman M. Harman, Peter D. Reaven

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)69-76
Number of pages8
JournalDiabetes, Obesity and Metabolism
Volume20
Issue number1
DOIs
StatePublished - Jan 2018
Externally publishedYes

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Insulin Resistance
Fatty Acids
Lipids
Diet
Placebos
Insulin
Glucose
Skeletal Muscle
Thioredoxins
AMP-Activated Protein Kinases
Vasodilation
Triglycerides
Liraglutide
Lunch
Proteins
Glucose Intolerance
Breakfast
Arterioles
Vascular Resistance
Cross-Over Studies

Keywords

  • insulin resistance
  • liraglutide
  • randomised trial

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Effect of liraglutide on dietary lipid-induced insulin resistance in humans. / Koska, Juraj; Lopez, Lizette; D'Souza, Karen; Osredkar, Tracy; Deer, James; Kurtz, Julie; Salbe, Arline D.; Harman, Sherman M.; Reaven, Peter D.

In: Diabetes, Obesity and Metabolism, Vol. 20, No. 1, 01.2018, p. 69-76.

Research output: Contribution to journalArticle

Koska, J, Lopez, L, D'Souza, K, Osredkar, T, Deer, J, Kurtz, J, Salbe, AD, Harman, SM & Reaven, PD 2018, 'Effect of liraglutide on dietary lipid-induced insulin resistance in humans', Diabetes, Obesity and Metabolism, vol. 20, no. 1, pp. 69-76. https://doi.org/10.1111/dom.13037
Koska, Juraj ; Lopez, Lizette ; D'Souza, Karen ; Osredkar, Tracy ; Deer, James ; Kurtz, Julie ; Salbe, Arline D. ; Harman, Sherman M. ; Reaven, Peter D. / Effect of liraglutide on dietary lipid-induced insulin resistance in humans. In: Diabetes, Obesity and Metabolism. 2018 ; Vol. 20, No. 1. pp. 69-76.
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