Betatrophin: A liver-derived hormone for the pancreatic β-cell proliferation

Abstract

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.

Keywords: Type 2 diabetes mellitus; Insulin resistance; Liver-derived betatrophin; Pancreas β-cell regeneration

Core tip: Yi et al have characterized a secreted protein named betatrophin that potently regulates β-cell proliferation. Evidently, betatrophin is identical to re-feeding-induced fat and liver protein, lipasin and atypical angiopoeitin-like 8, all of which were characterized as regulators of lipid homeostasis, by three independent groups of investigators. Yi et al were the first to demonstrate that hepatic expression of betatrophin in mice caused a dramatic surge in proliferation of the pancreatic β-cells with a concomitant improvement of their glucose tolerance. The discovery of a circulating hormone that specifically targets β-cell proliferation is a promising development towards a better clinical management of diabetes.