Harris R B, Mitchell T D, Yan X, Simpson J S, Redmann S M
Departments of Neuroscience and Biostatistics, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA.
Am J Physiol Regul Integr Comp Physiol. 2001 Jul;281(1):R115-32. doi: 10.1152/ajpregu.2001.281.1.R115.
Obese, diabetic C57BL/Ks db/db mice that lack the long-form leptin receptor exhibit no decrease in body weight or food intake when treated with leptin. Here we compared responses to leptin in two strains of db/db mice: C57BL/6J mice that are hyperglycemic and hyperinsulinemic and C57BL/Ks that are hyperglycemic and normo- or hypoinsulinemic. Chronic intraperitoneal infusion of 10 microgram leptin/day partially reversed hyperglycemia in C57BL/6J male mice but exaggerated the diabetic state of female mice. Bolus intraperitoneal injections of 40 microgram leptin/day did not effect glucose in either strain of male db/db mice, whereas chronic intraperitoneal infusion of 20 microgram leptin/day significantly reduced fasting blood glucose in male mice from both strains, especially C57BL/6J mice. Food intake, body weight, rectal temperature, and body fat did not change. Chronic intraperitoneal infusion of 10 microgram leptin/day significantly reduced body fat in lean db/+ C57BL/6J but not in C57BL/Ks mice. Thus peripherally administered leptin is active in mice that have only short-form leptin receptors, and the response is dependent on the method of leptin administration and the background strain.
缺乏长型瘦素受体的肥胖糖尿病C57BL/Ks db/db小鼠在接受瘦素治疗时体重和食物摄入量并未减少。在此，我们比较了两种db/db小鼠品系对瘦素的反应：血糖高且胰岛素高的C57BL/6J小鼠以及血糖高且胰岛素正常或偏低的C57BL/Ks小鼠。每天腹腔内慢性输注10微克瘦素可部分逆转C57BL/6J雄性小鼠的高血糖，但会加剧雌性小鼠的糖尿病状态。每天腹腔内推注40微克瘦素对两种品系的雄性db/db小鼠的血糖均无影响，而每天腹腔内慢性输注20微克瘦素可显著降低两种品系雄性小鼠的空腹血糖，尤其是C57BL/6J小鼠。食物摄入量、体重、直肠温度和体脂均未改变。每天腹腔内慢性输注10微克瘦素可显著降低瘦的db/+ C57BL/6J小鼠的体脂，但对C57BL/Ks小鼠无效。因此，外周给予的瘦素在仅具有短型瘦素受体的小鼠中具有活性，且反应取决于瘦素的给药方法和背景品系。
