AJP - Endocrinology and Metabolism, Vol 263, Issue 3 E550-E555, Copyright © 1992 by American Physiological Society
Interactions between insulin and glucocorticoids in the maintenance of genetic obesity
P. U. Dubuc
Sansum Medical Research Foundation, Santa Barbara, California 93105.
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.
