A modified liver enzyme with enhanced stability helps to control glycaemia

Abstract

Reducing insulin resistance in skeletal muscle is a promising potential strategy for controlling blood levels of glucose in people with type 2 diabetes mellitus (T2DM). A study published in Diabetologia now shows that treatment with HEXA–Fc (a protein created by fusing the liver enzyme hexosaminidase A (HEXA) with the fragment crystallizable (Fc) region of immunoglobulin G1) can promote glucose uptake by skeletal muscle in mice with obesity and T2DM.

Next, the researchers investigated which tissue HEXA–Fc localizes to after administration and tested the effects of HEXA–Fc on glycaemic control. They administered HEXA–Fc to wild-type mice that had been fed a high-fat diet to induce obesity, and then collected several types of tissue from the mice, including skeletal muscle, adipose tissue, hypothalamus and liver. They performed immunoblot analysis on these tissues and saw that there was more HEXA–Fc in the skeletal muscle than in any of the other tissues that were analysed. They also saw that although insulin tolerance did not change in obese mice treated with HEXA–Fc, these mice displayed a notable increase in glucose tolerance and decreased glucose-stimulated insulin secretion.