Sodium-potassium pump in cultured fibroblasts from obese donors; no evidence for an inherent decrease of basal or insulin-stimulated activity.
Na, K-ATPase activity may have a significant role in cellular thermogenesis. Reduced thermogenesis and an increased accumulation of unused calories in the form of fat could result from reduced basal or insulin-stimulated Na,K-ATPase activity in obese insulin-resistant man. We have previously demonstrated reduced Na,K-ATPase activity in intact red cells and their isolated membranes from obese humans. To determine if the reduced enzyme activity in obese subjects is the result of inherent cellular defects in the regulation of Na,K-pump activity, basal and insulin-stimulated rates of ouabain-inhibitable Rb uptake were measured in diploid fibroblasts from subjects with a range of body mass indices (BMI). Cell cultures were established from five extremely obese subjects (BMI greater than 40 kg/m2) with fasting hyperinsulinemia (38 +/- 6 microU/mL) and in four control (BMI less than 30 kg/m2) normoinsulinemic (14 +/- 3 microU/mL) subjects. Basal (17 +/- 3 v 23 +/- 2 nmol/L/min/10(10) cells +/- SEM) and maximal insulin-stimulated Na,K-pump activities (26 +/- 3 v 32 +/- 3 nmol/L/min/10(10) cells) were similar in the obese and control subjects. Maximal insulin stimulation for both groups was observed in four to eight minutes, and one-half maximal response required 2.5 ng/ml insulin. Cell density was negatively correlated with basal (r = 0.75, p less than 0.001) and maximally stimulated Na,K-pump activity (r = -0.73, p less than 0.001). Adjustment for this relationship did not influence the conclusions. Comparison of the results from the obese and control groups indicates (a) no evidence for an intrinsic cellular difference in basal Na,K-pump activity related to obesity and (b) no difference in insulin regulation of Na,K-pump activity, in fibroblasts from obese subjects.
D000328:Adult; D001693:Biological Transport, Active / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D009765:Obesity / Q000201:enzymology / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D011868:Radioisotopes; D012413:Rubidium; D012867:Skin / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D007328:Insulin; D011868:Radioisotopes; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium; D011188:Potassium