Insulin action kinetics in adipocytes from obese and noninsulin-dependent diabetes mellitus subjects: identification of multiple cellular defects in glucose transport.
Recent results from in vivo studies have shown that the kinetics of insulin action are impaired in lean and obese noninsulin-dependent diabetes mellitus (NIDDM) subjects as well as in obese nondiabetic subjects. We have measured the onset and loss of insulin action on glucose transport in adipocytes obtained from obese nondiabetic and obese NIDDM subjects to determine the contributions of obesity and diabetes to these cellular defects in insulin action. Basal and maximally insulin-stimulated rates of 3-O-methylglucose transport in adipocytes from obese and obese NIDDM subjects were reduced to 50% of the values in cells from normal subjects (P less than 0.05). The activation of glucose transport by insulin (4.3 nmol/L) was slower in cells from obese NIDDM patients. Half of the maximal insulin effect (A50) was reached by 23.0 +/- 5.0 min compared to 9.4 +/- 1.1 min in normal cells (P less than 0.05). Conversely, the deactivation of insulin-stimulated glucose transport upon removal of insulin was more rapid in adipocytes from the obese and obese NIDDM subjects. Half of the maximal insulin effect (D50) was lost by 12.4 +/- 1.7 min in obese NIDDM cells and by 8.9 +/- 1.9 min in obese subjects compared to 25.3 +/- 1.9 min in adipocytes from normal subjects (P less than 0.01). In conclusion, 1) basal and insulin-stimulated rates of glucose transport are similarly reduced in adipocytes from obese and obese NIDDM subjects; and 2) adipocytes from obese and obese NIDDM subjects display defects in the kinetics of insulin action, slower activation and accelerated deactivation, that mirror the defects measured in vivo. Both impairments in the kinetics of insulin action may contribute to the insulin resistance in these subject groups.
Ciaraldi
T P
TP
Department of Medicine, University of California School of Medicine, La Jolla 92093.
Molina
J M
JM
Olefsky
J M
JM
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001692:Biological Transport; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D009765:Obesity / Q000378:metabolism* / Q000473:pathology
D007328:Insulin; D005947:Glucose