The role of somatostatin in pathophysiology of obesity and diabetes mellitus

生长抑素在肥胖和糖尿病病理生理学中的作用

• 批准号: 60570529
• 负责人: SEINO Yutaka
• 金额: $ 1.09万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1985
• 资助国家: 日本
• 起止时间: 1985 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-60570529/
• 关键词: Somatostatin; Vagus; Cholinergic neuron; Non cholinergic neuron; Obesity

We have found previously that somatostatin secretion is enhanced and somatostatin metabolism is delayed in obese and diabetic animals, resulting in hypersomatostatinemia which may play an important role in pathophysiology of obesity and diabetes mellitus. Since somatostatin is thought to be neuropeptide, it is important to elucidate the mechanism of neural regulation of somatostatin secretion. We have developped a new in vitro procedure of the isolated rat pancreas or stomach with vagal innervation. Electrical vagal stimulation produced an inhibition in somatostatin release. When atropine was infused, somatostatin release induced by vagal was enhanced. In the presence of hexamethonium, vagal stimulation failed to affect somatostatin secretion. Propranolol did not influence somatostatin response to vagal stimulation as phentolamine did. Simultaneous administration of propranolol and phentholamine had no effect on somatostatin response. These findings suggest that somatostatin secretion is controlled not only a cholinergic inhibitory neuron but also by a noncholinergic, e.g. peptidergic stimulatory neuron, both of which is regulated through preganglionic vagal fibers via nicotinic receptor.

我们以前发现肥胖和糖尿病动物生长抑素分泌增加，生长抑素代谢延迟，导致高生长抑素血症，这可能在肥胖和糖尿病的病理生理学中起重要作用。由于生长激素抑制素被认为是一种神经肽，因此阐明生长激素抑制素分泌的神经调节机制具有重要意义。我们建立了一种新的离体大鼠胰或胃迷走神经支配的方法。电刺激迷走神经可抑制生长抑素的释放。注射阿托品后，迷走神经诱导的生长抑素释放增强。在六烃季铵的存在下，迷走神经刺激未能影响生长抑素分泌。普萘洛尔不影响生长抑素反应迷走神经刺激酚妥拉明。普萘洛尔和酚妥拉明同时给药对生长抑素反应无影响。这些结果表明，生长抑素的分泌不仅是由胆碱能抑制神经元，但也由非胆碱能，如肽能刺激神经元，这两个都是通过调节节前迷走神经纤维通过烟碱受体。

项目成果

M. Seno, Y. Seino, J. Takemura, S. Nishi, H. Ishida, N. Kitano, H. Imura, T. Taminato and H. Imura: "Comparison of somatostatin-28 and -14 clearance by the perfused rat liver" Can J Phys Pharm. 63. 62-67 (1985)

M. Seno、Y. Seino、J. Takemura、S. Nishi、H. Ishida、N. Kitano、H. Imura、T. Taminato 和 H. Imura：“灌注大鼠生长抑素-28 和 -14 清除率的比较

S. Nishi, Y. Seino, H. Ishida, M. Seno, T. Taminato, H. Sakurai and H. Imura: "Vagal regulation of insulin, glucagon and somatostatin secretion in vitro in the rat" J Clin Invest.

S. Nishi、Y. Seino、H. Ishida、M. Seno、T. Taminato、H. Sakurai 和 H. Imura：“大鼠体外胰岛素、胰高血糖素和生长抑素分泌的迷走神经调节”J Clin Invest。

Y. Seino, S. Nishi and H. Imura: "Vagal modulation of arginine- and glucagon-induced pancreatic somatostatin secretion" Life Sci. 37. 651-656 (1985)

Y. Seino、S. Nishi 和 H. Imura：“精氨酸和胰高血糖素诱导的胰腺生长抑素分泌的迷走神经调节”《生命科学》。

S. Nishi, Y. Seino, J. Takemura, H. Ishida, M. Seno, T. Chiba, C. Yanaihara, N. Yanaihara and H. Imura: "Vagal regulation of gastrin-releasing peptide (GRP), gastric somatostatin and gastrin secretion in vitro" Am J Physiol: Endocrinol and Metab. 248. E42

S. Nishi、Y. Seino、J. Takemura、H. Ishida、M. Seno、T. Chiba、C. Yanaihara、N. Yanaihara 和 H. Imura：“胃泌素释放肽 (GRP)、胃生长抑素的迷走神经调节

M.Seno;Y.Seino;J.Takemura;S.Nishi;H.Ishida;N.Kitano;H.Imura,T:Taminato;H.Imura: Can J Phys Pharm. 63. 62-67 (1985)

M.Seno；Y.Seino；J.Takemura；S.Nishi；H.Ishida；N.Kitano；H.Imura，T：Taminato；H.Imura：Can J Phys Pharm。