Glucosamine Inhibits Glucokinase In Vitro and Produces a Glucose-Specific Impairment of In Vivo Insulin Secretion in Rats
Glucosamine Inhibits Glucokinase In Vitro and Produces a Glucose-Specific Impairment of In Vivo Insulin Secretion in Rats
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葡萄糖胺在体外抑制葡萄糖激酶并对大鼠体内胰岛素分泌产生葡萄糖特异性损害
DOI：
10.2337/diab.43.10.1173
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发表时间：
1994
期刊：
影响因子：
7.7
通讯作者：
B. Dunning
中科院分区：
文献类型：
--
作者：
B. Balkan;B. Dunning
非胰岛素依赖型糖尿病（NIDDM）的一个特征是对静脉葡萄糖缺乏急性胰岛素反应，而对其他促分泌素的反应得以维持。据推测，葡萄糖感知受损源于β细胞葡萄糖激酶缺陷。目前尚不清楚胰腺葡萄糖激酶活性降低是否会产生类似于NIDDM中观察到的胰岛素分泌缺陷。在这项研究中，葡萄糖胺对葡萄糖激酶活性和胰岛功能的影响进行了评估，在体外和体内。氨基葡萄糖（5 mmol/l）可降低胰岛匀浆中的葡萄糖激酶活性，并降低离体胰岛对葡萄糖（200 mg/dl）的胰岛素反应，而对精氨酸（20 mmol/l，100 mg/dl葡萄糖）的反应不受影响。在清醒的正常大鼠中，氨基葡萄糖降低血浆胰岛素，随后增加血糖。在输注葡萄糖（10 mg·min-1·15 min）前10 min给予氨基葡萄糖可降低胰岛素反应。主要效应是相对于基础胰岛素水平降低，第一时相胰岛素反应减弱。精氨酸（10 mg·min-1·15 min）在两组中均诱导双相胰岛素释放。尽管氨基葡萄糖轻微降低了绝对胰岛素反应，但相对于输注前水平是正常的。在所有实验中，胰高血糖素分泌不受葡萄糖胺的影响。结果表明，葡萄糖胺在体外抑制β-细胞葡萄糖激酶活性。此外，葡糖胺损害葡萄糖诱导的胰岛素分泌，但不损害精氨酸诱导的胰岛素分泌。我们的结论是，葡萄糖胺，可能通过减少葡萄糖激酶活性，损害胰岛素分泌的方式在NIDDM中看到的。
A characteristic feature of non-insulin-dependent diabetes mellitus (NIDDM) is the lack of an acute insulin response to intravenous glucose with maintenance of the response to other secretagogues. It has been hypothesized that impaired glucose sensing stems from defective β-cell glucokinase. It remains unclear whether decreased pancreatic glucokinase activity will produce defects of insulin secretion similar to those observed in NIDDM. In this study, the effects of glucosamine on glucokinase activity and on islet function were assessed in vitro and in vivo. Glucosamine (5 mmol/l) reduced glucokinase activity in islet homogenate and diminished the insulin response to glucose (200 mg/dl) by isolated islets, whereas the response to arginine (20 mmol/l at 100 mg/dl glucose) was unaffected. In conscious normal rats, glucosamine lowered plasma insulin, followed by an increase in blood glucose. Administration of glucosamine 10 min before an infusion of glucose (10 mg · min−1 · 15 min) reduced the insulin response. The primary effect was an attenuation of the first-phase insulin response relative to the decreased basal insulin levels. Arginine (10 mg · min−1 · 15 min) induced biphasic insulin release in both groups. Although glucosamine slightly reduced the absolute insulin response, it was normal relative to preinfusion levels. In all experiments, glucagon secretion was unaffected by glucosamine. The results indicate that glucosamine inhibits β-cell glucokinase activity in vitro. In addition, glucosamine impairs glucose- but not arginine-induced insulin secretion. We conclude that glucosamine, probably via a reduction of glucokinase activity, impairs insulin secretion in a manner comparable to that seen in NIDDM.
影响因子：
15.9
作者：
WARD, WK;BOLGIANO, DC;PORTE, D
通讯作者：
PORTE, D
葡萄糖调节大鼠胰腺培养胰岛中的葡萄糖激酶活性。
DOI：
--
发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Liang,Y;Najafi,H;Matschinsky,FM
通讯作者：
Matschinsky,FM