Impaired insulin binding to isolated adipocytes in experimental diabetic ketoacidosis
Impaired insulin binding to isolated adipocytes in experimental diabetic ketoacidosis
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实验性糖尿病酮症酸中毒中胰岛素与分离脂肪细胞的结合受损
DOI：
10.1007/bf00281550
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发表时间：
1981
期刊：
影响因子：
8.2
通讯作者：
K. Alberti
中科院分区：
文献类型：
--
作者：
J. Whittaker;C. Cuthbert;V. Hammond;K. Alberti
摘要本文研究了链脲佐菌素糖尿病酮症酸中毒大鼠体内胰岛素敏感性及胰岛素与脂肪细胞的体外结合。体内胰岛素敏感性测量为每小时1 U/kg体重胰岛素输注后急性（20分钟）血糖下降与动脉血pH呈正相关（r=0.92, p < 0.01: n=38）。在pH < 6.9时，血糖没有下降。为了研究胰岛素与脂肪细胞的结合，将酮症酸中毒动物分为中度酮症酸中毒组（pH < 7.0）和重度酮症酸中毒组（pH < 6.9）。在pH 7.6-7.8时，酮症酸中毒和正常大鼠的细胞中胰岛素与脂肪细胞的结合最大。在所有ph值的研究中，糖尿病大鼠的总结合减少（p < 0.01），在严重糖尿病组中更明显（p < 0.001）。在pH 7.4时，糖尿病患者与正常大鼠相比，125i -胰岛素结合降低（0.89±0.14比2.0±0.24%，2×105细胞/ml: n=6, p < 0.01）；重度酮症酸中毒大鼠与中度酮症酸中毒大鼠相比，125i -胰岛素结合降低（0.5±0.08%/2×105细胞，n=6, p < 0.05）。平衡结合研究表明，两组糖尿病患者脂肪细胞的表观亲和力（KD = 2.8±0.2×10-9 mol/l，中度酮症酸中毒n=6; 2.5±0.3×10-9 mol/l，重度酮症酸中毒n=6）均较对照动物（KD = 1.8±0.15×10-9 mol/l, n=6）略有下降。Scatchard分析显示，受体浓度也有下降，严重酮症酸中毒组下降幅度更大。这些发现可以部分解释严重酮症酸中毒的胰岛素抵抗。
SummaryInsulin sensitivity in vivo and insulin binding in vitro to adipocytes have been studied in streptozotocin diabetic rats with ketoacidosis. Insulin sensitivity in vivo measured as the acute (20 min) fall in blood glucose in response to an insulin infusion of 1 U/kg body weight per hour correlated positively with arterial blood pH (r=0.92, p < 0.01: n=38). At pH < 6.9 there was no fall in blood glucose. For studies of insulin binding to adipocytes ketoacidotic animals were divided into a group with moderate ketoacidosis (pH > 7.0) and a second group with severe ketoacidosis (pH < 6.9). Insulin binding to adipocytes was maximal in cells from both ketoacidotic and from normal rats at pH 7.6–7.8. Total binding was decreased in the diabetic rats (p < 0.01) and this was more marked in the severely diabetic group (p < 0.001) at all pHs studied. At pH 7.4, 125I-insulin binding was decreased in diabetics compared with normal rats (0.89±0.14 versus 2.0±0.24% with 2×105 cells/ml: n=6; p < 0.01) and also in the severe compared with the moderate ketoacidotic rats (0.5± 0.08%/2×105 cells; n=6, p < 0.05). Equilibrium binding studies showed that there was a small decrease in apparent affinity in adipocytes from both groups of diabetics (KD = 2.8±0.2×10-9 mol/l, n =6 in moderate ketoacidosis; 2.5±0.3×10-9 mol/l, n=6 in severe ketoacidosis) compared with control animals (KD = 1.8±0.15×10-9 mol/l, n= 6). Scatchard analysis revealed that there was also a decrease in receptor concentration which was greater in the severely ketoacidotic group. These findings may explain in part the insulin resistance of severe ketoacidosis.