Obesity and
metabolic syndrome represent major public health problems, and are the biggest preventable causes of death worldwide.
Obesity is the leading risk factor for
type 2 diabetes mellitus (T2DM),
cardiovascular diseases and
non-alcoholic fatty liver disease.
Obesity-associated
insulin resistance, which is characterized by reduced uptake and utilization of
glucose in muscle, adipose and liver tissues, is a key predictor of
metabolic syndrome and T2DM. With increasing prevalence of
obesity in adults and children, the need to identify and characterize potential targets for treating
metabolic syndrome is imminent. Emerging evidence from animal models, clinical studies and cell lines studies suggest that
protein tyrosine phosphatase 1B (PTP1B), an
enzyme that negatively regulates
insulin signaling, is likely to be involved in the pathways leading to
insulin resistance. PTP1B is tethered to the cytosolic surface of endoplasmic reticulum (ER), an organelle that is responsible for folding, modification, and trafficking of
proteins. Recent evidence links the disruption of ER homeostasis, referred to as ER stress, to the pathogenesis of
obesity and T2DM. PTP1B has been recognized as an important player linking ER stress and
insulin resistance in obese subjects. This review highlights recent advances in the research related to the role of PTP1B in signal transduction processes implicated in pathophysiology of
obesity and
type 2 diabetes, and focuses on the potential therapeutic exploitation of PTP1B inhibitors for the management of these conditions.