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Functional Abnormality of the Pancreatic B Cells in terms of Proinsulin Secretion

胰腺 B 细胞胰岛素原分泌功能异常

基本信息

批准号：
02671107
负责人：
IWAMOTO Yasuhiko
金额：
$ 1.34万
依托单位：
Jichi Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02671107/
关键词：
Proinsulin Secretion Proinsulin insulin Ratio Pancreatic B cell Function NIDDM Borderline Glucose Intolerance (IGT)Family History of Diabetes Mellitus Oral Hypoglycemic Agent 糖尿病発症因子膵β細胞機能インスリン非依在性糖尿病糖負荷試験境昇型肥満

项目摘要

Previously we reported the disproportionate elevation of serum proinsulin (PI)/insulin (I) ratio in patients with diabetes mellitus, and PI/I ratio seems to be one of clinical indicators of the functional state of the pancreatic B cells. In this study, in order to investigate the effects of several diabetogenic factors on proinsulin secretion, we measured serum proinsulin both at fasting and after oral glucose load in obese subjects with various glucose tolerance, in aged subjects with normal glucose tolerance, and in the borderline glucose intolerant subjects with and without family history of diabetes mellitus. In addition, we studied the effect of sulfonylurea therapy on proinsulin secretion in NIDDM patients.1. In obese subjects both insulin and proinsulin are elevated and the PI/I ratio remained unchanged, suggesting that each B cell seems to function normally in obese subjects.2. There was no significant difference in serum PI/I ratio between those with and without family history of diabetes mellitus.3. Proinsulin secretion is disproportionately increased in aged subjects as compared to that in young subjects, suggesting the functional abnormality of the pancreatic B cells in aged subjects.4. Disproportionate elevation of proinsulin in borderline glucose intolerance was more marked in low insulin responders (insulinogenic index 0.4). In combination with the previous reports that low insulin responders are known at higher risk to develop diabetes, the elevation of PI/I may provide an additional marker to predict the risk of development of NIDDM.5. After improvement of glycemic control by sulfonylurea therapy, the elevation of serum PI/I ratio in NIDDM patients could be reduced, suggesting that the relative hypersecretion of proinsulin is a reversible change rather than an irreversible change.

我们曾报道糖尿病患者血清胰岛素原（PI）/胰岛素（I）比值不成比例地升高，PI/I比值似乎是反映胰腺B细胞功能状态的临床指标之一。为了探讨几种致糖尿病因素对胰岛素原分泌的影响，我们测定了不同糖耐量的肥胖者、糖耐量正常的老年人、有或无糖尿病家族史的临界糖耐量者空腹和口服葡萄糖负荷后的血清胰岛素原。此外，我们还研究了磺脲类药物治疗对NIDDM患者胰岛素原分泌的影响.在肥胖患者中，胰岛素和胰岛素原均升高，PI/I比值保持不变，表明肥胖患者的每个B细胞似乎功能正常。有糖尿病家族史与无糖尿病家族史者的PI/I比值无显著性差异.老年人胰岛素原的分泌与年轻人相比不成比例地增加，提示老年人胰腺B细胞功能异常.在临界葡萄糖耐受不良中，胰岛素原不成比例的升高在低胰岛素应答者中更为显著（胰岛素生成指数0.4）。结合先前的报道，低胰岛素应答者已知具有更高的糖尿病风险，PI/I的升高可能提供预测NIDDM风险的额外标志物。经磺脲类药物改善血糖控制后，NIDDM患者PI/I比值的升高可降低，提示胰岛素原的相对高分泌是一种可逆的变化，而非不可逆的变化。