NORMAL INSULIN SENSITIVITY DURING THE PHASE OF GLUCOSE-INTOLERANCE BUT INSULIN RESISTANCE AT THE ONSET OF DIABETES IN THE SPONTANEOUSLY DIABETIC BB RAT
NORMAL INSULIN SENSITIVITY DURING THE PHASE OF GLUCOSE-INTOLERANCE BUT INSULIN RESISTANCE AT THE ONSET OF DIABETES IN THE SPONTANEOUSLY DIABETIC BB RAT
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DOI：
10.1007/bf00297448
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发表时间：
1989-12-01
期刊：
影响因子：
8.2
通讯作者：
GIRARD, J
中科院分区：
文献类型：
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作者：
BAUDON, MA;FERRE, P;GIRARD, J
在易患糖尿病的BB大鼠中，30%至50%的动物经历胰腺B细胞的自身免疫破坏，导致短期的葡萄糖耐受不良，随后突然发生糖尿病。我们已经研究了葡萄糖耐受不良期和糖尿病的发病是否与胰岛素敏感性的变化，使用正常血高胰岛素钳夹结合[3- 3 H]葡萄糖输注。葡萄糖不耐受大鼠通过每四天进行一次口服葡萄糖负荷后一小时的短暂糖尿来检测。在这些大鼠中研究的胰岛素敏感性在检测后的第二天是正常的。其他糖尿病倾向的BB大鼠每天进行测试，并在糖尿的第一天进行研究。在基础状态下，糖尿病大鼠的葡萄糖产生增加（11.3 ± 0.01）。1.1相对于7.1 .+-。0.8 mg. min-1. mg ~（-1），p < 0.05。糖尿病大鼠和对照大鼠的组织葡萄糖利用率相似（8.3 ± 0.01）。0.5相对于7.1 .+-。0.8 mg. min-1. kg-1），尽管糖尿病大鼠中的高血糖症高三倍。在高胰岛素钳夹期间，糖尿病大鼠和对照大鼠的血糖被钳夹在6.1-6.6 mmol/l。在糖尿病大鼠中，在抑制肝葡萄糖产生和刺激葡萄糖利用的次最大（200 μ U/ml）和最大（1500 μ U/ml）胰岛素浓度下观察到胰岛素敏感性降低。糖尿病大鼠血浆中未检测到抗胰岛素自身抗体。在钳夹研究期间，对照组和糖尿病大鼠中胰高血糖素、儿茶酚胺、酮体和脂肪酸的血浆浓度相似。我们的研究结果表明，基础胰岛素浓度的降低是糖尿病BB大鼠在糖尿病发病时胰岛素抵抗的原因，无论是直接还是通过增加血糖。
In diabetes-prone BB rats, 30 to 50% of animals undergo autoimmune destruction of the pancreatic B-cells leading to a short period of glucose intolerance, followed by an abrupt onset of diabetes. We have examined whether the glucose intolerance period and the onset of diabetes are associated with changes in insulin sensitivity, using the euglycaemic hyperinsulinaemic clamp coupled with [3-3H] glucose infusion. Glucose intolerant rats were detected by a transient glycosuria one hour after an oral glucose load performed every four days. Insulin sensitivity studied in these rats the day following their detection was normal. Other diabetes-prone BB rats were tested daily and studied on the first day of glycosuria. In the basal state, glucose production was increased in diabetic rats (11.3 .+-. 1.1 vs 7.1 .+-. 0.8 mg .cntdot. min-1 .cntdot. mg-1, p < 0.05). Tissue glucose utilization was similar in diabetic and control rats (8.3 .+-. 0.5 vs 7.1 .+-. 0.8 mg .cntdot. min-1 .cntdot. kg-1) despite a three fold higher glycaemia in the diabetic rats. During the hyperinsulinaemic clamps, glycaemia was clamped at 6.1-6.6 mmol/l in diabetic and control rats. A decreased insulin sensitivity was observed in diabetic rats at submaximal (200 .mu.U/ml) and maximal (1500 .mu.U/ml) insulin concentrations for both inhibition of hepatic glucose production and stimulation of glucose utilization. No autoantibodies against insulin could be detected in the plasma of diabetic rats. Plasma concentrations of glucagon, catecholamines, ketone bodies and fatty acids were similar in control and diabetic rats during the clamp studies. Our results suggest that the decrease of basal insulin concentration is responsible for the insulin resistance in the diabetic BB rat at onset of diabetes, either directly or through the increased glycaemia.