Dechenes C J, Verchere C B, Andrikopoulos S, Kahn S E
Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle 98195, USA.
Am J Physiol. 1998 Nov;275(5):E785-91. doi: 10.1152/ajpendo.1998.275.5.E785.
Aging is associated with an increased risk of type 2 diabetes. To determine whether the insulin resistance of aging is associated with an increase in amylin release or whether amylin release parallels the reduction in insulin release, we studied 10 older (72 +/- 2 yr) and 9 young (25 +/- 1 yr) subjects. Insulin sensitivity was quantified as the insulin sensitivity index (SI) and B cell function as the acute insulin and amylin responses to iv glucose (AIRg and AARg, respectively) and iv arginine at a glucose level of >25 mM (AIRmax and AARmax). To account for the effect of SI to modulate B cell function, we calculated SI x B cell function. Older subjects were insulin resistant (SI: 4.6 +/- 0.8 vs. 8.6 +/- 1.4 x 10(-5) min-1/pM, P < 0.05). Acute responses to glucose [AIRg (older vs. young): 420 +/- 106 vs. 537 +/- 87 pM; AARg: 6.5 +/- 1.7 vs. 9.0 +/- 1.5 pM] and arginine (AIRmax: 1,096 +/- 203 vs. 1,572 +/- 307 pM; AARmax: 14.0 +/- 3.5 vs. 16.5 +/- 2.4 pM) did not differ despite the difference in SI. When adjusted for SI, insulin responses were reduced in older subjects (SI x AIRg: 1.54 +/- 0.29 vs. 4.10 +/- 0. 63 x 10(-2) min-1, P = 0.001; SI x AIRmax: 4.03 +/- 0.52 vs. 12.7 +/- 2.9 x 10(-2) min-1, P < 0.01), as was amylin release (SI x AARg: 2.46 +/- 0.59 vs. 6.85 +/- 0.95 x 10(-4) min-1, P < 0.001; SI x AARmax: 4.71 +/- 0.52 vs. 13.5 +/- 2.2 x 10(-4) min-1, P < 0.001). Amylin and insulin release was proportionate, with a molar ratio of 1.5% in older and 1.4% in young subjects. Thus aging is associated with parallel impairments in the adaptation of insulin and amylin release to insulin resistance. It is unlikely that an alteration in amylin release contributes to the increased risk of type 2 diabetes.
衰老与2型糖尿病风险增加相关。为了确定衰老引起的胰岛素抵抗是否与胰岛淀粉样多肽释放增加有关，或者胰岛淀粉样多肽释放是否与胰岛素释放减少平行，我们研究了10名老年受试者（72±2岁）和9名年轻受试者（25±1岁）。胰岛素敏感性通过胰岛素敏感性指数（SI）进行量化，B细胞功能则通过静脉注射葡萄糖（分别为AIRg和AARg）和静脉注射精氨酸（葡萄糖水平>25 mM时为AIRmax和AARmax）后的急性胰岛素和胰岛淀粉样多肽反应来评估。为了考虑SI对B细胞功能的调节作用，我们计算了SI×B细胞功能。老年受试者存在胰岛素抵抗（SI：4.6±0.8 vs. 8.6±1.4×10⁻⁵ min⁻¹/pM，P<0.05）。尽管SI存在差异，但对葡萄糖的急性反应（AIRg（老年与年轻）：420±106 vs. 537±87 pM；AARg：6.5±1.7 vs. 9.0±1.5 pM）和对精氨酸的急性反应（AIRmax：1096±203 vs. 1572±307 pM；AARmax：14.0±3.5 vs. 16.5±2.4 pM）并无差异。在根据SI进行调整后，老年受试者的胰岛素反应降低（SI×AIRg：1.54±0.29 vs. 4.10±0.63×10⁻² min⁻¹，P = 0.001；SI×AIRmax：4.03±0.52 vs. 12.7±2.9×10⁻² min⁻¹，P<0.01），胰岛淀粉样多肽释放也降低（SI×AARg：2.46±0.59 vs. 6.85±0.95×10⁻⁴ min⁻¹，P<0.001；SI×AARmax：4.71±0.52 vs. 13.5±2.2×10⁻⁴ min⁻¹，P<0.001）。胰岛淀粉样多肽和胰岛素的释放是成比例的，老年受试者的摩尔比为1.5%，年轻受试者为1.4%。因此，衰老与胰岛素和胰岛淀粉样多肽释放对胰岛素抵抗的适应性平行受损有关。胰岛淀粉样多肽释放的改变不太可能导致2型糖尿病风险增加。
