Protein tyrosine phosphatases: molecular switches in metabolism and diabetes

• Genetic polymorphisms for particular PTPs are associated with altered risk of diabetes.
• PTPs affect β cell and immune cell function associated with autoimmune diabetes.
• PTPs have specific activities in the regulation of leptin signaling and appetite.
• Hepatocytes use different PTP members in a receptor-dependent manner.
• PTPs are promising drug targets for the treatment of obesity and diabetes.

Protein tyrosine phosphatases (PTPs) are a large family of enzymes that generally oppose the actions of protein tyrosine kinases (PTKs). Genetic polymorphisms for particular PTPs are associated with altered risk of both type 1 diabetes (T1D) and type 2 diabetes (T2D). Moreover, recent evidence suggests that PTPs play crucial roles in metabolism. They can act as regulators of liver homeostasis, food intake, or immune-mediated pancreatic β cell death. In this review we describe the mechanisms by which different members of the non-receptor PTP (PTPN) family influence metabolic physiology. This ‘metabolic job’ of PTPs is discussed in depth and the role of these proteins in different cell types compared. Understanding the pathways regulated by PTPs will provide novel therapeutic strategies for the treatment of diabetes.