Dubuc P U
Sansum Medical Research Foundation, Santa Barbara, California 93105.
Am J Physiol. 1992 Sep;263(3 Pt 1):E550-5. doi: 10.1152/ajpendo.1992.263.3.E550.
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.
在3月龄的C57BL/6 ob/ob小鼠中，于链脲佐菌素（STZ）或STZ加肾上腺切除术后6周对血糖调节和身体组成进行了检测。STZ抑制了ob/ob小鼠的躯体生长，但在免疫反应性胰岛素（IRI）降至完整ob/ob小鼠的40%（100微单位/毫升）之前，并未引起高血糖。当IRI接近瘦小鼠的水平（40微单位/毫升）时，ob/ob小鼠出现严重高血糖（800+毫克/分升）及其他I型糖尿病后遗症，但仍保持与未治疗的肥胖小鼠相同的50%体脂率。相比之下，瘦小鼠中的STZ糖尿病导致体脂不成比例地减少。在STZ之前进行肾上腺切除术导致与单独使用STZ相同的胰岛素缺乏、生长抑制和高血糖，但联合治疗后，体脂百分比与IRI成比例下降。因此，一组严重糖尿病的肾上腺切除术后的STZ肥胖小鼠，其IRI非常低（20微单位/毫升），其体脂含量和去脂体重与体重匹配的瘦小鼠相当。数据表明，皮质醇增多症而非高胰岛素血症在很大程度上导致了ob/ob小鼠的肥胖。然而，在缺乏肾上腺糖皮质激素的情况下，或者可能仅在其恢复正常时，高胰岛素血症似乎是维持过多身体能量储存所必需的。
