title: Lipid-induced insulin resistance does not impair insulin access to skeletal muscle.
abstract: Elevated plasma free fatty acids (FFA) induce insulin resistance in skeletal muscle. Previously, we have shown that experimental insulin resistance induced by lipid infusion prevents the dispersion of insulin through the muscle, and we hypothesized that this would lead to an impairment of insulin moving from the plasma to the muscle interstitium. Thus, we infused lipid into our anesthetized canine model and measured the appearance of insulin in the lymph as a means to sample muscle interstitium under hyperinsulinemic euglycemic clamp conditions. Although lipid infusion lowered the glucose infusion rate and induced both peripheral and hepatic insulin resistance, we were unable to detect an impairment of insulin access to the lymph. Interestingly, despite a significant, 10-fold increase in plasma FFA, we detected little to no increase in free fatty acids or triglycerides in the lymph after lipid infusion. Thus, we conclude that experimental insulin resistance induced by lipid infusion does not reduce insulin access to skeletal muscle under clamp conditions. This would suggest that the peripheral insulin resistance is likely due to reduced cellular sensitivity to insulin in this model, and yet we did not detect a change in the tissue microenvironment that could contribute to cellular insulin resistance.
authors: Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California Cathryn.Kolka@cshs.org.
authors: Cathryn M
authors: http://orcid.org/0000-0002-6636-7062
authors: CM
authors: Kolka
authors: Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Joyce M
authors: JM
authors: Richey
authors: Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Ana Valeria B
authors: AV
authors: Castro
authors: Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Josiane L
authors: JL
authors: Broussard
authors: Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Viorica
authors: V
authors: Ionut
authors: Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors: Richard N
authors: RN
authors: Bergman
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015309:Glucose Clamp Technique; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008055:Lipids / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008055:Lipids
keywords: glucose; insulin; interstitium; lipid; skeletal muscle