ANGPTL8 (betatrophin) role in diabetes and metabolic diseases

Diabetes is a major disease worldwide that is reaching epidemic levels. Its increased prevalence as well as its association with a high number of complications such as cardiovascular diseases, nephropathy, and retinopathy makes it an important disease for investigation. ANGPTL8 is a recently identified hormone that has been associated with two functionally important processes in the development of type 2 diabetes, insulin resistance as well as lipid metabolism. Initial work has shown that ANGPTL8 was expressed in liver, white adipose, and brown adipose tissues. ANGPTL8 regulates the activity of lipoprotein lipase, which is a key enzyme in lipoprotein lipolysis pathway through its direct interaction with ANGPTL3. It has been also reported that it regulates the replication of β-cells in response to insulin resistance. As a result, many recent studies have focused on the association of ANGPTL8 with diabetes and obesity as well as its association with various metabolic markers in order to better understand its physiological role in glucose homeostasis and lipid metabolism. In this review, we will highlight some of the key clinical findings, mainly from human studies, that investigated the role of ANGPTL8 in metabolic diseases such as diabetes, obesity, and the metabolic syndrome.