HEXA-FC protein therapy increases skeletal muscle glucose uptake and improves glycaemic control in mice with insulin resistance and in a mouse model of type 2 diabetes

Abstract

Aims/hypothesis: Type 2 diabetes is a chronic metabolic disorder characterised by insulin resistance and sustained hyperglycaemia, and is a major cause of blindness, kidney failure, heart attacks and stroke. Our team has recently identified hexosaminidase A (HEXA) as an endocrine factor secreted by the liver that regulates sphingolipid metabolism in skeletal muscle. Specifically, HEXA converts GM2 to GM3 gangliosides within cell-surface lipid rafts. Remodelling of ganglioside composition by HEXA enhances IGF1 signalling in skeletal muscle, increasing muscle glucose uptake and improving blood glucose control. Methods: We produced a long-acting HEXA-FC fusion protein (murine HEXA and the fragm..