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
Cell signaling, ER stress, insulin resistance, insulin signaling, leptin signaling, obesity, PTP1B, PTP1B inhibitors,
type 2 diabetes.
Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USA.