Lipid-induced insulin resistance is not mediated by impaired transcapillary transport of insulin and glucose in humans.

Abstract

Increased lipid availability reduces insulin-stimulated glucose disposal in skeletal muscle, which is generally explained by fatty acid-mediated inhibition of insulin signaling. It remains unclear whether lipids also impair transcapillary transport of insulin and glucose, which could become rate controlling for glucose disposal. We hypothesized that lipid-induced insulin resistance is induced by inhibiting myocellular glucose uptake and not by interfering with the delivery of insulin or glucose. We measured changes in interstitial glucose and insulin in skeletal muscle of healthy volunteers during intravenous administration of triglycerides plus heparin or glycerol during physiologic and supraphysiologic hyperinsulinemia, by combining microdialysis with oral glucose tolerance tests and euglycemic-hyperinsulinemic clamps. Lipid infusion reduced insulin-stimulated glucose disposal by ~70% (P < 0.05) during clamps and dynamic insulin sensitivity by ~12% (P < 0.05) during oral glucose loading. Dialysate insulin and glucose levels were unchanged or even transiently higher (P < 0.05) during lipid than during glycerol infusion, whereas regional blood flow remained unchanged. These results demonstrate that short-term elevation of free fatty acids (FFAs) induces insulin resistance, which in skeletal muscle occurs primarily at the cellular level, without impairment of local perfusion or transcapillary transport of insulin and glucose. Thus, vascular effects of FFAs are not rate controlling for muscle insulin-stimulated glucose disposal.

• Authors: Julia Szendroedi, Martin Frossard, Nikolas Klein, Christian Bieglmayer, Oswald Wagner, Giovanni Pacini, Janette Decker, Peter Nowotny, Markus Müller, Michael Roden
• Journal: Diabetes (Diabetes) Vol. 61 Issue 12 Pg. 3176-80 (Dec 2012) ISSN: 1939-327X [Electronic] United States
• PMID: 22891212 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Fatty Acids, Nonesterified
• Insulin
• Triglycerides
• Heparin
• Glucose

Topics

• Biological Transport (drug effects)
• Fatty Acids, Nonesterified (blood)
• Glucose (metabolism)
• Heparin (pharmacology)
• Humans
• Insulin (metabolism)
• Insulin Resistance (physiology)
• Male
• Microdialysis
• Muscle, Skeletal (drug effects, metabolism)
• Regional Blood Flow (drug effects)
• Triglycerides (pharmacology)