Kahn S E, Verchere C B, Andrikopoulos S, Asberry P J, Leonetti D L, Wahl P W, Boyko E J, Schwartz R S, Newell-Morris L, Fujimoto W Y
Division of Metabolism, Endocrinology and Nutrition, University of Washington and VA Puget Sound Health Care System, Seattle 98108, USA.
Diabetes. 1998 Apr;47(4):640-5. doi: 10.2337/diabetes.47.4.640.
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 ALI, IRI, and glucose (G) at 30 min after oral glucose ingestion was used to calculate deltaALI/deltaG and deltaIRI/deltaG as measures of beta-cell function. Overall glucose metabolism was assessed as the incremental glucose area (glucose AUC) 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 deltaIRI/deltaG (NGT, 119+/-10.3; IGT, 60.7+/-7.1; type 2 diabetes, 49.7 +/-5.4 pmol/l; P < 0.0001) and deltaALI/deltaG (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 deltaIRI/deltaG or deltaALI/deltaG, and glucose metabolism, assessed as glucose AUC, was nonlinear and inverse in nature, with r2 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.
胰岛淀粉样变是2型糖尿病的一个特征性表现。其主要成分是正常β细胞分泌产物胰淀素，即胰岛淀粉样多肽（IAPP）。为了确定胰淀素释放增加或不成比例是否可以解释2型糖尿病中淀粉样沉积的倾向，我们按照世界卫生组织标准，对94名糖耐量正常（NGT；n = 56）、糖耐量受损（IGT；n = 10）和2型糖尿病（n = 28）的日裔美国人进行口服葡萄糖负荷试验，测量了血浆胰淀素样免疫反应性（ALI）和免疫反应性胰岛素（IRI）的释放。口服葡萄糖后30分钟时ALI、IRI和葡萄糖（G）的增量用于计算ΔALI/ΔG和ΔIRI/ΔG，作为β细胞功能的指标。口服葡萄糖耐量试验2小时期间的葡萄糖增量面积（葡萄糖AUC）用于评估总体葡萄糖代谢情况。正如预期的那样，空腹（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小时时（NGT，6.7±0.1；IGT，9.4±0.3；2型糖尿病，13.2±0.5 mmol/l；P < 0.0001）的血浆葡萄糖浓度在IGT和2型糖尿病患者中均升高。口服葡萄糖后，所有受试者的血浆IRI和ALI均升高，但葡萄糖耐量降低的个体中这些增量较低，这在ΔIRI/ΔG（NGT，119±10.3；IGT，60.7±7.1；2型糖尿病，49.7±5.4 pmol/l；P < 0.0001）和ΔALI/ΔG（NGT；2.6±0.2；IGT，1.8±0.3；2型糖尿病，1.2±0.1 pmol/l；P < 0.0001）中得到体现。此外，30分钟增量ALI和IRI反应的这些降低是成比例的，使得三组之间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%；无显著性差异）。此外，以ΔIRI/ΔG或ΔALI/ΔG衡量的β细胞功能与以葡萄糖AUC评估的葡萄糖代谢之间的关系本质上是非线性且呈负相关的，r2值分别为0.38（P < 0.0001）和0.33（P < 0.0001）。我们得出结论，IGT和2型糖尿病患者β细胞功能降低包括IRI和ALI释放的成比例降低。因此，2型糖尿病中胰岛淀粉样变的发生不太可能是ALI释放增加的结果。
