针对糖尿病病理生理缺陷的双相调控-默沙东ppt课件.ppt

* * * T2DM患者ac功能紊乱可以认为是ac对葡萄糖敏感性受损，一方面表现为绝对空腹胰高血糖素水平高于非糖尿病受试者。空腹高胰高血糖素血症的存在，有助于增加肝糖输出率。ac的葡萄糖敏感性受损的另一表现为高血糖诱导抑制胰高血糖素释放的作用丧失。也就是说在T2DM患者葡萄糖灌注或负荷，或高碳水化合物餐后，血浆胰高血糖素水平较非DM受试者下降幅度较少。Ac功能紊乱最重要的一个临床表现为对低血糖的适当反应缺失。由于ac对葡萄糖的敏感性受损，所以在血糖水平下降时，胰高血糖素分泌不足增加严重低血糖的风险，而在空腹和餐后胰高血糖素分泌过度，进而促进T2DM高血糖的进展。 * Ac功能紊乱不只出现在T2DM患者，而是在疾病的早期阶段IGT阶段就已经出现胰岛素分泌减少，胰高血糖素抑制不足，所致肝糖输出显著增加。这种现象在肥胖和非肥胖患者相似。 Rate of endogenous glucose appearance and mean arterial plasma insulin and glucagon concentrations before and after ingestion of oral glucose at time 0 in individuals with IGT (?) and with NGT (°). In non-diabetic individuals, increased insulin secretion and suppression of glucagon both contribute to the reduction in hepatic glucose output after a meal. Figure 3 illustrates how diminished glucagon suppression and reduced insulin secretion correlate with significantly increased hepatic glucose output in an IGT population compared with healthy individuals ( p 0.02). These effects are observed in both non-obese and obese individuals. * 这张幻灯进一步解释T2DM中ac对葡萄糖的敏感性减低。在T2DM患者中，对急性胰高糖素反应的抑制达最大值的一半时所需的血糖水平较NGT显著增加，提示了T2DM患者aC对葡萄糖抑制作用的敏感性是减弱的。 the plasma glucose level required for half-maximal suppression of the AGRarg is substantially higher in diabetic subjects than in normal, glucose-tolerant subjects, suggesting that the sensitivity of the alpha cell to the suppressive effects of glucose is decreased [29]. * * 30多年前， Unger and Orci 就提出了“双激素假说”解释糖尿病中高血糖的起源。他们证明了除了相对和绝对的胰岛素分泌不足外，相对高胰高血糖素血症也是糖尿病进程的关键因素。 * * * Insulin and Glucagon Dynamics in Response to Meals Are Abnormal in Type 2 Diabetes A clinical study described postprandial glucose, insulin, and glucagon dynamics in patients with type 2 diabetes mellitus (n=12) vs nondiabetic control subjects (n=11).1 After a large carbohydrate meal, mean plasma glucose concentrations rose from 228 mg/100 mL to a peak of 353 mg/100 mL in patients with type 2 diabetes mellitus, compared with an increase from 84 mg/100 mL to a peak of 137 mg/100 mL in nondiabetic subje