β-Cell function and islet morphology in normal, obese, and obese β-cell mass-reduced Gottingen minipigs
β-Cell function and islet morphology in normal, obese, and obese β-cell mass-reduced Gottingen minipigs
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DOI：
10.1152/ajpendo.00352.2004
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发表时间：
2005-02-01
影响因子：
5.1
通讯作者：
Rolin, B
中科院分区：
文献类型：
--
作者：
Larsen, MO;Juhl, CB;Rolin, B
在此，我们在小型猪中桥接β细胞功能和形态。我们假设β细胞功能障碍的不同方面存在于肥胖症和β细胞质量减少的肥胖症中，通过使用脉冲式胰岛素分泌作为早期标志物。在长期（19 - 20个月）肥胖（n = 5）和肥胖β细胞减少[烟酰胺+链脲佐菌素（STZ），n = 5]小型猪和正常对照组中研究了β细胞功能（葡萄糖和精氨酸刺激加上基线和葡萄糖夹带的脉冲式胰岛素分泌）和胰岛形态学的测量，这些小型猪代表了向2型糖尿病发展的不同阶段。令人惊讶的是，肥胖者对葡萄糖和精氨酸的急性胰岛素反应（AIR）是正常的。（0.3 g/kg葡萄糖：AIR = 246 +/- 119对比对照组中的255 +/- 61 pM; 67 mg/kg精氨酸：AIR = 230 +/- 124对比对照组中的214 +/- 85 pM），但在肥胖-STZ动物中降低（0.3g/kg葡萄糖：AIR = 22 +/- 36，P < 0.01;精氨酸：AIR = 87 +/- 92 pM，P < 0.05相对于对照）。肥胖患者的基线脉动胰岛素分泌减少，（59 +/- 16 vs.对照组76 +/- 16%，P < 0.05），肥胖-STZ动物中更是如此（43 +/-13%，P < 0.01），而在肥胖动物中，（近似熵：0.85 +/- 0.14对比对照组1.13 +/- 0.13，P < 0.01）。β-细胞质量（mg/kg体重）在肥胖动物中是正常的，而在肥胖-STZ动物中是减少的，在两组中都有胰腺脂肪浸润。总之，肥胖和胰岛素抵抗与β细胞功能的普遍降低无关，但胰岛素分泌的动力学受到干扰。数据表明β细胞功能障碍的发展顺序，三组代表从正常生理学到糖尿病的进展阶段，并评估脉动性作为β细胞功能障碍的单一最敏感标志物。
Herein, we bridge beta-cell function and morphology in minipigs. We hypothesized that different aspects of beta-cell dysfunction are present in obesity and obesity with reduced beta-cell mass by using pulsatile insulin secretion as an early marker. Measures for beta-cell function ( glucose and arginine stimulation plus baseline and glucose-entrained pulsatile insulin secretion) and islet morphology were studied in long-term ( 19 - 20 mo) obese ( n = 5) and obese beta-cell-reduced [ nicotinamide + streptozotocin (STZ), n = 5] minipigs and normal controls, representing different stages in the development toward type 2 diabetes. Acute insulin response ( AIR) to glucose and arginine were, surprisingly, normal in obese (0.3 g/kg glucose: AIR = 246 +/- 119 vs. 255 +/- 61 pM in control; 67 mg/kg arginine: AIR = 230 +/- 124 vs. 214 +/- 85 pM in control) but reduced in obese-STZ animals ( 0.3 g/kg glucose: AIR = 22 +/- 36, P < 0.01; arginine: AIR = 87 +/- 92 pM, P < 0.05 vs. control). Baseline pulsatile insulin secretion was reduced in obese ( 59 +/- 16 vs. 76 +/- 16% in control, P < 0.05) and more so in obese-STZ animals ( 43 +/- 13%, P < 0.01), whereas regularity during entrainment was increased in obese animals ( approximate entropy: 0.85 +/- 0.14 vs. 1.13 +/- 0.13 in control, P < 0.01). beta-Cell mass (mg/kg body wt) was normal in obese and reduced in obese-STZ animals, with pancreatic fat infiltration in both groups. In conclusion, obesity and insulin resistance are not linked with a general reduction of beta-cell function, but dynamics of insulin secretion are perturbed. The data suggest a sequence in the development of beta-cell dysfunction, with the three groups representing stages in the progression from normal physiology to diabetes, and assessment of pulsatility as the single most sensitive marker of beta-cell dysfunction.