EFFECTS OF GROWTH HORMONE-RELEASING HORMONE ON THE SECRETION OF ISLET HORMONES AND ON GLUCOSE-HOMEOSTASIS IN LEAN AND GENETICALLY OBESE-DIABETIC (OB/OB) MICE AND NORMAL RATS
EFFECTS OF GROWTH HORMONE-RELEASING HORMONE ON THE SECRETION OF ISLET HORMONES AND ON GLUCOSE-HOMEOSTASIS IN LEAN AND GENETICALLY OBESE-DIABETIC (OB/OB) MICE AND NORMAL RATS
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DOI：
10.1677/joe.0.1230019
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发表时间：
1989-10-01
影响因子：
4
通讯作者：
BUCHANAN, KD
中科院分区：
文献类型：
--
作者：
BAILEY, CJ;WILKES, LC;BUCHANAN, KD
本文研究了合成人生长激素释放激素（1-40）（hGHRH-40）对瘦型和遗传性肥胖糖尿病（ob/ob）小鼠及正常大鼠内分泌胰腺功能和葡萄糖稳态的影响。在5.6和16.7mmol葡萄糖/l下，向来自正常瘦小鼠的孵育胰岛中加入1 μ mol hGHRH-40/l分别增加90%和37%的胰岛素释放。较低浓度的hGHRH-40不影响胰岛素释放。在5.6mmol葡萄糖/l时，hGHRH-40（1 μ mol/l）使胰多肽释放增加50%。一系列浓度的hGHRH-40（1 nmol/l-1 μ mol/l）在5.6mmol葡萄糖/l时使胰高血糖素释放减少42-73%，在16.7mmol葡萄糖/l时减少38-70%。在5.6mmol葡萄糖/l时，生长抑素释放被1 μ mol hGHRH-40/l增加（8倍），但在1 nmol hGHRH-40/l时，生长抑素释放被减少（> 50%）。在16.7mmol葡萄糖/升时，0.01-1 μ mol hGHRH-40/l增加生长抑素释放（3 - 4倍），但1 nmol hGHRH-40/l产生50%的减少。在体内，将hGHRH-40（50 μ g/kg体重i. p.）对禁食的瘦型和肥胖/肥胖小鼠没有改变葡萄糖和胰岛素的基础血浆浓度，或葡萄糖和胰岛素对伴随的腹膜内葡萄糖激发的反应。对麻醉大鼠静脉注射hGHRH-40（20 μ g/kg体重）增加了肝门静脉中胰岛素的血浆浓度。较低剂量的hGHRH-40（0.2 μ g/kg）是无效的，并且两种剂量的hGHRH-40都不改变血浆葡萄糖。结果表明，hGHRH-40对胰岛激素的分泌发挥剂量依赖性作用，但这似乎不足以对血浆葡萄糖稳态产生可测量的作用。
The effect of synthetic human growth hormone-releasing hormone(1-40) (hGHRH-40) on the function of the endocrine pancreas and on glucose homeostasis in lean and genetically obese-diabetic (ob/ob) mice and normal rats has been examined. The addition of 1 .mu.mol hGHRH-40/l to incubated islets from normal lean mice increased insulin release by 90 and 37% at 5.6 and 16.7 mmol glucose/l respectively. Lower concentrations of hGHRH-40 did not affect insulin release. hGHRH-40 (1 .mu.mol/l) increased pancreatic polypeptide release by 50% at 5.6 mmol glucose/l. A range of concentrations of hGHRH-40 (1 nmol/l-1 .mu.mol/l) reduced glucagon release by 42-73% at 5.6 mmol glucose/l, and by 38-70% at 16.7 mmol glucose/l. Somatostatin release was increased (eightfold) by 1 .mu.mol hGHRH-40/l at 5.6 mmol glucose/l, but at 1 nmol hGHRH-40/l somatostatin release was reduced (by > 50%). At 16.7 mmol glucose/litre 0.01-1 .mu.mol hGHRH-40/l increased somatostatin release (three- to fourfold), but 1 nmol hGHRH-40/l produced a reduction of 50%. In vivo, administration of hGHRH-40 (50 .mu.g/kg body weight i.p.) to fasted lean and ob/ob mice did not alter basal plasma concentrations of glucose and insulin, or the glucose and insulin response to a concomitant i.p. glucose challenge. Intravenous injection of hGHRH-40 (20 .mu.g/kg body weight) to anaesthetized rats increased plasma concentrations of insulin in the hepatic portal vein. A lower dose of hGHRH-40 (0.2 .mu.g/kg) was ineffective, and neither dose of hGHRH-40 altered plasma glucose. The results indicate that hGHRH-40 exerts dose-dependent effects on the secretion of islet hormones, but this does not appear to be sufficient to produce measurable effects on plasma glucose homeostasis.