Lipid and insulin infusion-induced skeletal muscle insulin resistance is likely due to metabolic feedback and not changes in IRS-1, Akt, or AS160 phosphorylation
Andrew J Hoy, Amanda E Brandon, Nigel Turner, Matthew J Watt, Clinton R Bruce, Gregory J Cooney, Edward W Kraegen
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | AMER PHYSIOLOGICAL SOC | Published : 2009
Type 2 diabetes is characterized by hyperlipidemia, hyperinsulinemia, and insulin resistance. The aim of this study was to investigate whether acute hyperlipidemia-induced insulin resistance in the presence of hyperinsulinemia was due to defective insulin signaling. Hyperinsulinemia (approximately 300 mU/l) with hyperlipidemia or glycerol (control) was produced in cannulated male Wistar rats for 0.5, 1 h, 3 h, or 5 h. The glucose infusion rate required to maintain euglycemia was significantly reduced by 3 h with lipid infusion and was further reduced after 5 h of infusion, with no difference in plasma insulin levels, indicating development of insulin resistance. Consistent with this finding,..View full abstract
Awarded by National Institute of Diabetes and Digestive and Kidney Diseases
Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
This study was funded by grants from the National Health and Medical Research Council (NHMRC) of Australia and National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-067509. A. J. Hoy is supported by an Australian Postgraduate Award from the University of New South Wales. N. Turner and M. J. Watt are supported by Career Development Awards from the NHMRC of Australia. C. R. Bruce is supported by NHMRC Peter Doherty Postdoctoral Fellowship 325645. G. J. Cooney and E. W. Kraegen are supported by the NHMRC of Australia Research Fellowships Scheme.