Reduced amylin release is a characteristic of impaired glucose tolerance and type 2 diabetes in Japanese Americans
Reduced amylin release is a characteristic of impaired glucose tolerance and type 2 diabetes in Japanese Americans
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DOI：
10.2337/diabetes.47.4.640
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发表时间：
1998-04-01
期刊：
影响因子：
7.7
通讯作者：
Fujimoto, WY
中科院分区：
文献类型：
--
作者：
Kahn, SE;Verchere, CB;Fujimoto, WY
胰岛淀粉样蛋白是 2 型糖尿病的一个特征。其主要成分是正常β细胞分泌产物胰岛淀粉样多肽（IAPP）。为了确定胰岛淀粉样蛋白释放增加或不成比例是否可以解释 2 型糖尿病中淀粉样蛋白沉积的倾向，我们测量了 94 名具有正常糖耐量 (NGT；n = 56)、糖耐量受损 (IGT；n = 10) 和世界卫生组织定义的 2 型糖尿病 (n = 28) 的 94 名日裔美国人受试者中口服葡萄糖负荷后的血浆胰岛淀粉样蛋白样免疫反应性 (ALI) 和免疫反应性胰岛素 (IRI) 释放。组织标准。口服葡萄糖摄入后 30 分钟 AI、I、IRI 和葡萄糖 (G) 的增量增加用于计算 Delta ALI/Delta G 和 Delta IRI/Delta G，作为 β 细胞功能的测量。总体葡萄糖代谢通过口服葡萄糖耐量试验 2 小时期间增量葡萄糖面积（葡萄糖 AUG）进行评估。正如预期的那样，空腹时（NGT，5.0 +/- 0.4；IGT，5.5 +/- 0.1；2 型糖尿病，6.2 +/- 0.3 mmol/l；P < 0.0001）和 2 小时（NGT，6.7 +/- 0.1；IGT，9.4 +/- 0.3；2 型糖尿病，13.2 +/- 0.3）时的血浆葡萄糖浓度0.5 mmol/l；P < 0.0001）在 IGT 和 2 型糖尿病患者中升高。响应葡萄糖摄入，所有受试者的血浆 IRI 和 ALI 均增加，但这些增量在糖耐量降低的个体中较低，如 Delta IRI/Delta G（NGT，119 +/- 10.3；IGT，60.7 +/- 7.1；2 型糖尿病，49.7 +/- 5.4 pmol/l；P < 0.0001）和 Delta ALI/Delta G（NGT， 2.6 +/- 0.2；IGT，1.8 +/- 0.3；2 型糖尿病，1.2 +/- 0.1 pmol/l；P < 0.0001）。此外，30 分钟增量 ALI 和 IRI 反应的减少是成比例的，因此三组中 ALI 与 IRI 的摩尔比没有差异（NGT，2.6 +/- 0.2；IGT，2.9 +/- 0.3；2 型糖尿病，2.9 +/- 0.3%；NS）。此外，β细胞功能（以 Delta IRI/Delta G 或 Delta ALI/Delta G 测量）与葡萄糖代谢（以葡萄糖 AUG 评估）之间的关系本质上是非线性和反比的，r(2) 值分别为 0.38 (P < 0.0001) 和 0.33 (P < 0.0001)。我们的结论是，IGT 和 2 型糖尿病导致的 β 细胞功能降低包括 IRI 和 ALI 释放的相应减少。因此，2 型糖尿病中胰岛淀粉样蛋白的形成不太可能是 ALI 释放增加的结果。
Islet amyloid is a characteristic feature of type 2 diabetes. Its major component is the normal beta-cell secretory product amylin, or islet amyloid polypeptide (IAPP). To determine whether increased or disproportionate release of amylin may explain the propensity for amyloid deposition in type 2 diabetes, we measured plasma amylin-like immunoreactivity (ALI) and immunoreactive insulin (IRI) release in response to an oral glucose load in 94 Japanese-American subjects with normal glucose tolerance (NGT; n = 56), impaired glucose tolerance (IGT; n = 10), and type 2 diabetes (n = 28) as defined by World Health Organization criteria. The incremental increase In AI,I, IRI, and glucose (G) at 30 min after oral glucose ingestion was used to calculate Delta ALI/Delta G and Delta IRI/Delta G as measures of beta-cell function. Overall glucose metabolism was assessed as the incremental glucose area (glucose AUG) during the 2 h of the oral glucose tolerance test. As expected, plasma glucose concentrations at both fasting (NGT, 5.0 +/- 0.4; IGT, 5.5 +/- 0.1; type 2 diabetes, 6.2 +/- 0.3 mmol/l; P < 0.0001) and 2 h (NGT, 6.7 +/- 0.1; IGT, 9.4 +/- 0.3; type 2 diabetes, 13.2 +/- 0.5 mmol/l; P < 0.0001) were elevated in individuals with IGT and type 2 diabetes. In response to glucose ingestion, plasma IRI and ALI increased in all subjects, but these increments were lower in individuals with reduced glucose tolerance, as reflected in the Delta IRI/Delta G (NGT, 119 +/- 10.3; IGT, 60.7 +/- 7.1; type 2 diabetes, 49.7 +/- 5.4 pmol/l; P < 0.0001) and Delta ALI/Delta G (NGT, 2.6 +/- 0.2; IGT, 1.8 +/- 0.3; type 2 diabetes, 1.2 +/- 0.1 pmol/l; P < 0.0001). Moreover, these reductions in the 30-min incremental ALI and IRI responses were proportionate such that the molar ratio of ALI to IRI was not different among the three groups (NGT, 2.6 +/- 0.2; IGT, 2.9 +/- 0.3; type 2 diabetes, 2.9 +/- 0.3%; NS). Further, the relationship between beta-cell function, measured as either Delta IRI/Delta G or Delta ALI/Delta G, and glucose metabolism, assessed as glucose AUG, was nonlinear and inverse in nature, with r(2) values of 0.38 (P < 0.0001) and 0.33 (P < 0.0001), respectively. We conclude that the reduced beta-cell function of IGT and type 2 diabetes includes proportionate reductions in both IRI and ALI release. Thus, it is unlikely that the development of islet amyloid in type 2 diabetes is the result of increased release of ALI.