Insulin-receptor kinase activity of adipose tissue from morbidly obese humans with and without NIDDM.
We have determined glucose transport, insulin binding, and insulin-receptor kinase activity in adipose tissue from morbidly obese patients with and without non-insulin-dependent diabetes mellitus (NIDDM). The insulin sensitivity and responsiveness of glucose transport in freshly isolated adipocytes were significantly reduced in NIDDM subjects compared with nondiabetics. This was due in part to decreased insulin binding in adipocytes. Reduced specific 125I-labeled insulin binding was also observed in crude detergent extracts and partially purified insulin receptors from adipose tissue. In addition, the basal and insulin-stimulated tyrosine-specific protein kinase activity per milligram of protein was significantly decreased in NIDDM patients compared with nondiabetics. The differences between maximally insulin-stimulated and basal kinase activities expressed by insulin-binding activity were also significantly reduced in NIDDM subjects. We conclude that insulin resistance in morbidly obese patients with NIDDM is due to both insulin-binding and postbinding defects. One of the postbinding defects in NIDDM appears to be impaired insulin-receptor kinase activity of fat tissue.
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism
D007328:Insulin; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D005947:Glucose