Havel P J, Uriu-Hare J Y, Liu T, Stanhope K L, Stern J S, Keen C L, Ahrén B
Department of Nutrition, University of California, Davis 95616, USA.
Am J Physiol. 1998 May;274(5):R1482-91. doi: 10.1152/ajpregu.1998.274.5.R1482.
Evidence for regulation of circulating leptin by insulin is conflicting. Diabetes was induced in rats with streptozotocin (STZ; 40 mg.kg(-1).day(-1) x 2 days) to examine the effect of insulin-deficient diabetes and insulin treatment on circulating leptin. After 12 wk, plasma leptin concentrations in untreated rats were all < 0.4 ng/ml versus 4.9 +/- 0.9 ng/ml in control animals (P < 0.005). In rats treated with subcutaneous insulin implants for 12 wk, which reduced hyperglycemia by approximately 50%, plasma leptin was 2.1 +/- 0.6 ng/ml, whereas leptin concentrations were 6.0 +/- 1.6 ng/ml in insulin-implanted rats receiving supplemental injections of insulin for 4 days to normalize plasma glucose (P < 0.005 vs. STZ untreated). In a second experiment, plasma leptin was monitored at biweekly intervals during 12 wk of diabetes. In rats treated with insulin implants, plasma leptin concentrations were inversely proportional to glycemia (r = -0.64; P < 0.0001) and unrelated to body weight (P = 0.40). In a third experiment, plasma leptin concentrations were examined very early after the induction of diabetes. Within 24 h after STZ injection, plasma insulin decreased from 480 +/- 30 to 130 +/- 10 pM (P < 0.0001), plasma glucose increased from 7.0 +/- 0.2 to 24.8 +/- 0.5 mM, and plasma leptin decreased from 3.2 +/- 0.2 to 1.2 +/- 0.1 ng/ml (delta = -63 +/- 3%, P < 0.0001). In a subset of diabetic rats treated with insulin for 2 days, glucose decreased to 11.7 +/- 3.9 mM and leptin increased from 0.5 +/- 0.1 to 2.9 +/- 0.6 ng/ml (P < 0.01) without an effect on epididymal fat weight. The change of leptin was correlated with the degree of glucose lowering (r = 0.75, P < 0.05). Thus insulin-deficient diabetes produces rapid and sustained decreases of leptin that are not solely dependent on weight loss, whereas insulin treatment reverses the hypoleptinemia. We hypothesize that decreased glucose transport into adipose tissue may contribute to decreased leptin production in insulin-deficient diabetes.
胰岛素对循环中瘦素的调节作用，相关证据存在矛盾。通过给大鼠注射链脲佐菌素（STZ；40mg·kg⁻¹·天⁻¹×2天）诱导糖尿病，以研究胰岛素缺乏型糖尿病及胰岛素治疗对循环中瘦素的影响。12周后，未治疗大鼠的血浆瘦素浓度均<0.4ng/ml，而对照动物为4.9±0.9ng/ml（P<0.005）。皮下植入胰岛素12周的大鼠，血糖降低约50%，血浆瘦素为2.1±0.6ng/ml；而接受补充胰岛素注射4天以使血糖正常化的胰岛素植入大鼠，瘦素浓度为6.0±1.6ng/ml（与未治疗的STZ大鼠相比，P<0.005）。在第二个实验中，糖尿病12周期间每两周监测一次血浆瘦素。胰岛素植入大鼠的血浆瘦素浓度与血糖呈负相关（r=-0.64；P<小0.0001），与体重无关（P=0.40）。在第三个实验中，糖尿病诱导后很早即检测血浆瘦素浓度。STZ注射后24小时内，血浆胰岛素从480±30降至130±10pM（P<0.0001），血浆葡萄糖从7.0±0.2升至24.8±0..5mM，血浆瘦素从3.2±0.2降至1.2±0.1ng/ml（变化量=-63±3%，P<0.0001）。在一组糖尿病大鼠中，胰岛素治疗2天，血糖降至11.7±3.9mM，瘦素从0.5±0.1升至2.9±0.6ng/ml（P<0.01），对附睾脂肪重量无影响。瘦素变化与血糖降低程度相关（r=0.75，P<0.05）。因此，胰岛素缺乏型糖尿病使瘦素迅速且持续降低，这并非仅依赖于体重减轻，而胰岛素治疗可逆转低瘦素血症。我们推测，胰岛素缺乏型糖尿病中脂肪组织葡萄糖转运减少可能导致瘦素产生减少。
