Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA.
Cell Cycle. 2011 Dec 15;10(24):4217-24. doi: 10.4161/cc.10.24.18595.
Rapamycin prolongs healthy lifespan in yeast, flies and mammals and delays age-related diseases, including cancer and atherosclerosis. Rapamycin is considered for prevention of diabetic complications, such as retinopathy and nephropathy, and acute treatment with rapamycin decreases insulin resistance. However, under certain conditions, chronic administration of rapamycin may cause glucose intolerance and even provoke type II diabetes. This does not fit logically with its potential effects against diabetic complications. This also seems puzzling, because calorie restriction (CR) can prevent type II diabetes and its complications, and rapamycin mimics CR. It was somehow forgotten that almost two centuries ago, Claude Bernard discovered "starvation diabetes," as shown later, characterized by glucose intolerance, decreased insulin, increased lipoproteins and ketones, gluconeogenesis and hepatic resistance to insulin. This reversible condition is not true diabetes: it does not lead to diabetic complications, and CR extends healthy lifespan. If rapamycin is a CR-mimetic, no wonder it may, in certain models, induce "hunger diabetes." But will rapamycin prevent true type II diabetes? Here are some answers.
雷帕霉素延长酵母、苍蝇和哺乳动物的健康寿命，并延缓与年龄相关的疾病，包括癌症和动脉粥样硬化。雷帕霉素被认为可预防糖尿病并发症，如视网膜病变和肾病，急性使用雷帕霉素可降低胰岛素抵抗。然而，在某些情况下，长期使用雷帕霉素可能导致葡萄糖不耐受，甚至引发 2 型糖尿病。这与它预防糖尿病并发症的潜在作用在逻辑上不符。这也似乎令人费解，因为热量限制（CR）可以预防 2 型糖尿病及其并发症，而雷帕霉素模拟 CR。不知怎的，人们忘记了大约两个世纪前，克劳德·伯纳德发现了“饥饿性糖尿病”，如后来所表明的，其特征是葡萄糖不耐受、胰岛素减少、脂蛋白和酮体增加、糖异生和肝对胰岛素的抵抗。这种可逆的情况并不是真正的糖尿病：它不会导致糖尿病并发症，CR 延长了健康寿命。如果雷帕霉素是一种 CR 模拟物，那么在某些模型中，它可能会导致“饥饿性糖尿病”也就不足为奇了。但是雷帕霉素会预防真正的 2 型糖尿病吗？以下是一些答案。
