Interactions between insulin and glucocorticoids in the maintenance of genetic obesity.
Glucoregulation and body composition were examined in 3-mo-old C57BL/6 ob/ob mice 6 wk after streptozotocin (STZ) or STZ plus adrenalectomy. STZ depressed somatic growth in ob/ob mice but did not cause hyperglycemia until immunoreactive insulin (IRI) was 40% (100 microU/ml) that of intact ob/ob mice. When IRI approached that of lean mice (40 microU/ml), ob/ob mice displayed severe hyperglycemia (800+ mg/dl) and other sequelae of type I diabetes but still maintained the same 50% body fat as untreated obese mice. In contrast, STZ diabetes in lean mice caused disproportionate reductions in body fat. Adrenalectomy before STZ led to the same insulinopenia, depressed growth, and hyperglycemia as STZ alone, but, after combined treatment, percent body fat declined in proportion to IRI. Thus a subgroup of severely diabetic adrenalectomized STZ obese mice with very low IRI (20 microU/ml) had body fat contents and fat-free masses equal to those of weight-matched lean mice. The data suggest that hypercorticoidism rather than hyperinsulinemia is largely responsible for obesity in ob/ob mice. However, in the absence of adrenal glucocorticoids, or perhaps with just their normalization, hyperinsulinemia appears necessary for maintaining excessive body energy stores.
Dubuc
P U
PU
Sansum Medical Research Foundation, Santa Barbara, California 93105.
D000273:Adipose Tissue / Q000187:drug effects; D000315:Adrenalectomy; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition; D001835:Body Weight / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D005938:Glucocorticoids / Q000502:physiology*; D006943:Hyperglycemia / Q000139:chemically induced; D007328:Insulin / Q000097:blood / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D013311:Streptozocin / Q000494:pharmacology
D001786:Blood Glucose; D005938:Glucocorticoids; D007328:Insulin; D013311:Streptozocin