Showing papers by "Jerrold M. Olefsky published in 1989"
TL;DR: The results suggest that human adipocytes contain two distinct receptor populations, both of which bind insulin but only one of which is capable of insulin-stimulated tyrosine phosphorylation.
Abstract: We used anti-insulin-receptor and anti-phosphotyrosine antibodies to elucidate the mechanism of decreased insulin-receptor tyrosine kinase activity observed in subjects with non-insulin-dependent diabetes mellitus (NIDDM). Lectin-purified insulin receptors were labeled with 125I-labeled NAPA-DP-insulin and autophosphorylated in the presence of 500 microM unlabeled ATP. Immunoprecipitation occurred in 43 +/- 8% of the autophosphorylated, 125I-labeled receptors from nondiabetic subjects with anti-phosphotyrosine antibodies in contrast to 100% immunoprecipitation with anti-insulin-receptor antibodies. Anti-phosphotyrosine antibodies immunoprecipitated only 14 +/- 6% of NIDDM receptors (P less than .05 vs. nondiabetic receptors). A significant correlation existed between maximal insulin-stimulated receptor tyrosine kinase activity and the proportion of receptors immunoprecipitated by anti-phosphotyrosine antibodies (r = .76, P less than .01). These results suggest that human adipocytes contain two distinct receptor populations, both of which bind insulin but only one of which is capable of insulin-stimulated tyrosine phosphorylation. In nondiabetic subjects, 40-50% of the receptors that bind insulin are capable of insulin-stimulated tyrosine autophosphorylation. The proportion of receptors that bind insulin but are incapable of insulin-stimulated tyrosine autophosphorylation is increased in NIDDM; the magnitude of this increase correlated with the magnitude of the decrease in kinase activity.
42 citations
TL;DR: The slower overall rates of activation of maximal insulin-stimulated glucose transport observed in adipocytes from obese subjects mirror the slower rates of stimulation of glucose disposal in vivo, which suggests that the in vivo findings are caused by a cellular abnormality in insulin action at a step beyond the binding of insulin to its receptor.
Abstract: Recent studies from our laboratory have shown that the rate at which insulin activates glucose disposal in vivo is much slower in obese subjects compared with lean controls To determine if this was caused by an abnormality in activation of insulin-stimulated glucose transport at the cellular level, we measured the rate at which insulin stimulated glucose transport in human adipocytes from obese volunteers Basal rates of 3-O-methylglucose transport in the absence of insulin were lower (020 +/- 004 vs 040 +/- 011 pmol10(-5) cells10 s-1, P less than 25) in adipocytes from obese subjects (n = 10) than in lean control subjects (n = 5), but this did not achieve statistical significance Maximal insulin-stimulated (4300 pM insulin) glucose transport rates were significantly decreased in obesity (281 +/- 081 vs 115 +/- 020 pmol10(-5) cells10 s-1, P less than 005) It took longer for adipocytes from obese subjects to achieve half-maximal activation of insulin-stimulated glucose transport than those from lean subjects (15 +/- 2 vs 94 +/- 12 min, P less than 05) The slower overall rates of activation of maximal insulin-stimulated glucose transport observed in adipocytes from obese subjects mirror the slower rates of stimulation of glucose disposal in vivo, which suggests that the in vivo findings are caused by a cellular abnormality in insulin action at a step beyond the binding of insulin to its receptor(ABSTRACT TRUNCATED AT 250 WORDS)
36 citations
TL;DR: Study of variations in the number of insulin receptor and insulin receptor mRNA levels in (Hep G2) cells in response to growth and insulin treatment demonstrates that the increase in insulin receptor number/cell in growth-arrested cells is paralleled by an increase inulin receptor mRNA content with no change in the receptor degradation rates.
36 citations