Development of obesity in Zucker rats. Early insulin resistance in muscles but normal sensitivity in white adipose tissue.
Euglycemic-hyperinsulinemic clamps were performed on 4- and 12-wk-old anesthetized lean and obese Zucker rats. During the clamp studies, total glucose production and utilization were assessed with a 3-[3H]glucose perfusion, whereas local glucose utilization was determined by measuring 2-deoxy-1-[3H]glucose 6-phosphate accumulation in various tissues. In the basal state, 4 wk-old obese rats were hyperinsulinemic (159 +/- 8 vs. 82 +/- 9 microU/ml), whereas glucose turnover rate was similar to that observed in lean rats (14.9 +/- 1.9 vs. 12.5 +/- 1.9 mg X min-1 X kg-1). Glucose utilization was identical in skeletal muscles, whereas it was increased in white adipose tissue of obese rats (22 +/- 4 vs. 8 +/- 2 ng X min-1 X mg-1). At plasma insulin level of 500 microU/ml, glucose production was totally suppressed in both groups, whereas overall glucose utilization was slightly less in 4-wk-old obese than in lean rats. This was due to a reduced stimulation of glucose utilization in skeletal muscles and brown adipose tissue. In contrast, glucose utilization in periovarian white adipose tissue was similarly increased in lean and obese rats. For a maximal insulin concentration (1500 microU/ml), all the differences were abolished between lean and obese young Zucker rats. In older (12-wk-old) obese rats, glucose utilization in various tissues was markedly reduced at maximal insulin level compared with that observed in age-matched lean animals.(ABSTRACT TRUNCATED AT 250 WORDS)
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D005260:Female; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker
D007328:Insulin; D005947:Glucose