Insulin resistance in the heart: studies on isolated cardiocytes of genetically obese Zucker rats.
Isolated cardiac myocytes from lean and genetically obese (fa/fa) Zucker rats were used to study cellular alterations related to the obesity syndrome in this tissue. Scatchard analysis of insulin binding data suggested a reduction in the number of low affinity sites in cells from obese rats; in contrast, an unaltered high affinity segment with Kd values of 5.7 +/- 0.6 and 4.5 +/- 0.7 X 10(-10) mol/liter (n = 4) in lean and obese rats, respectively, has been observed. Insulin internalization, as estimated from the amount of increased cell-associated radioactivity in chloroquine-treated cells, was decreased by 70% from 12.8 fmol insulin/10(6) cells X 120 min in lean rats to 3.8 fmol/10(6) cells X 120 min in obese rats. Determinations of initial velocities of 3-O-methylglucose influx were used for assessing glucose transport activity. Basal activity of the glucose transport system was reduced in cells from obese animals. This was found to be due to a decreased maximum velocity of the carrier with corresponding values of 69.8 +/- 5.2 and 38.3 +/- 3.2 nmol/10 sec X 10(6) cells (n = 3) in cardiocytes from lean and obese rats, respectively. Glucose transport exhibited an unaltered sensitivity toward stimulation by insulin, but an impaired responsiveness in cardiocytes from obese rats. The data suggest involvement of both receptor and postreceptor defects in the development of an insulin-resistant state in cardiac muscle.
D019325:3-O-Methylglucose; D000818:Animals; D001692:Biological Transport; D004351:Drug Resistance; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D009206:Myocardium / Q000473:pathology*; D009765:Obesity / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D011924:Rats, Zucker; D013552:Swine
D007328:Insulin; D008757:Methylglucosides; D019325:3-O-Methylglucose; D005947:Glucose