Rajendra Raghow, Department of Veterans Affairs Medical Center, Memphis, TN 38104, United States.
World J Diabetes. 2013 Dec 15;4(6):234-7. doi: 10.4239/wjd.v4.i6.234.
The pancreatic β-cell failure which invariably accompanies insulin resistance in the liver and skeletal muscle is a hallmark of type-2 diabetes mellitus (T2DM). The persistent hyperglycemia of T2DM is often treated with anti-diabetic drugs with or without subcutaneous insulin injections, neither of which mimic the physiological glycemic control seen in individuals with fully functional pancreas. A sought after goal for the treatment of T2DM has been to harness the regenerative potential of pancreatic β-cells that might obviate a need for exogenous insulin injections. A new study towards attaining this aim was reported by Yi et al, who have characterized a liver-derived protein, named betatrophin, capable of inducing pancreatic β-cell proliferation in mice. Using a variety of in vitro and in vivo methods, Yi et al, have shown that betatrophin was expressed mainly in the liver and adipose tissue of mice. Exogenous expression of betatrophin in the liver led to dramatic increase in the pancreatic β-cell mass and higher output of insulin in mice that also concomitantly elicited improved glucose tolerance. The authors discovered that betatrophin was also present in the human plasma. Surprisingly, betatrophin has been previously described by three other names, i.e., re-feeding-induced fat and liver protein, lipasin and atypical angiopoeitin-like 8, by three independent laboratories, as nutritionally regulated liver-enriched factors that control serum triglyceride levels and lipid metabolism. Yi et al demonstration of betatrophin, as a circulating hormone that regulates β-cell proliferation, if successfully translated in the clinic, holds the potential to change the course of current therapies for diabetes.
胰腺 β 细胞的衰竭在肝脏和骨骼肌中伴随着胰岛素抵抗，这是 2 型糖尿病（T2DM）的标志。T2DM 的持续性高血糖通常用抗糖尿病药物治疗，无论是否皮下注射胰岛素，这些药物都不能模拟具有完全功能胰腺的个体的生理血糖控制。T2DM 治疗的一个追求目标是利用胰腺 β 细胞的再生潜力，从而避免对外源胰岛素注射的需求。Yi 等人报告了一项实现这一目标的新研究，他们描述了一种名为 betatrophin 的肝源蛋白，该蛋白能够在小鼠中诱导胰腺 β 细胞增殖。使用各种体外和体内方法，Yi 等人表明 betatrophin主要在小鼠的肝脏和脂肪组织中表达。肝脏中 betatrophin 的外源性表达导致胰腺 β 细胞质量的急剧增加和胰岛素产量的增加，同时还引起葡萄糖耐量的改善。作者发现 betatrophin也存在于人类血浆中。令人惊讶的是，betatrophin 之前已被三个独立实验室分别命名为 re-feeding-induced fat and liver protein、lipasin 和 atypical angiopoeitin-like 8，是营养调节的富含肝脏的因子，可控制血清甘油三酯水平和脂质代谢。如果 Yi 等人能够证明 betatrophin 是一种循环激素，可调节 β 细胞增殖，如果成功转化为临床应用，那么它有可能改变当前糖尿病治疗的进程。
