胰高血糖素受体拮抗改善胰岛功能与胰岛素抵抗引起的小鼠高脂饮食。
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Winzell女士、品牌CL、Wierup N, Sidelmann UG, Sundler F,西村E, Ahren B
胰高血糖素受体拮抗改善胰岛功能与胰岛素抵抗引起的小鼠高脂饮食。
Diabetologia。2007年7月,50 (7):1453 - 62。2007年5月4日Epub。
- PubMed ID
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17479245 (在PubMed]
- 文摘
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目的/假说:胰高血糖素分泌增加预测葡萄糖耐量的恶化,导致高血糖症和高胰高血糖素水平在2型糖尿病。因此,抑制胰高血糖素的行动或许是潜在的新目标降低高血糖症。在这里,我们调查是否慢性治疗胰高血糖素受体拮抗剂(GRA)改善胰岛功能障碍在雌性小鼠高脂饮食(HFD)。材料与方法:HFD 8周后,小鼠治疗小分子草(300毫克/公斤,填喂法一次每天)长达30天。胰岛素分泌研究后口服给药和静脉注射葡萄糖和静脉注射精氨酸后胰高糖素分泌的功能。胰岛形态学检查和胰岛素分泌和葡萄糖氧化以孤立的小岛。结果:空腹血浆葡萄糖水平降低草(6.0 + / - 0.2 vs 7.4 + / - 0.5更易/ l;p = 0.017)。急性静脉注射葡萄糖胰岛素反应增强(1300 + / - 110 vs 790 + / - 64 pmol / l;p < 0.001)。 The early insulin response to oral glucose was reduced in mice on HFD + GRA (1,890 +/- 160 vs 3,040 +/- 420 pmol/l; p = 0.012), but glucose excursions were improved. Intravenous arginine significantly increased the acute glucagon response (129 +/- 12 vs 36 +/- 6 ng/l in controls; p < 0.01), notably without affecting plasma glucose. GRA caused a modest increase in alpha cell mass, while beta cell mass was similar to that in mice on HFD + vehicle. Isolated islets displayed improved glucose-stimulated insulin secretion after GRA treatment (0.061 +/- 0.007 vs 0.030 +/- 0.004 pmol islet(-1) h(-1) at 16.7 mmol/l glucose; p < 0.001), without affecting islet glucose oxidation. CONCLUSIONS/INTERPRETATION: Chronic glucagon receptor antagonism in HFD-fed mice improves islet sensitivity to glucose and increases insulin secretion, suggesting improvement of key defects underlying impaired glucose tolerance and type 2 diabetes.