Implication of a novel Gla-containing protein, Gas6 in the pathogenesis of insulin resistance, impaired glucose homeostasis, and inflammation: A review

Growth arrest specific 6 (Gas6), a vitamin K-dependent protein plays a significant role in the regulation of cellular homeostasis via binding with TAM-receptor tyrosine kinases. Several studies reported the role of Gas6 in cancer, glomerular injury, obesity, and inflammation, however, very little is known about its role in insulin resistance (IR) and impaired glucose metabolism. Majority of the studies reported an inverse correlation of Gas6 protein levels or gene polymorphism with plasma glucose, HbA1c, IR, and inflammatory cytokines among type 2 diabetes (T2D) and obese subjects. However, few studies reported a positive correlation of Gas6 protein levels or gene polymorphism with IR and inflammation among obese subjects. This review for the first time provides an overview of the association of Gas6 protein levels or gene polymorphism with IR, glucose intolerance, and inflammation among T2D and obese subjects. This review also depicts the probable mechanism underlying the association of Gas6 with glucose intolerance and inflammation. The outcome of this review will increase the understanding about the role of Gas6 in the pathogenesis of IR, glucose intolerance and inflammation and that should in turn lead to the design of clinical interventions to improve glucose metabolism and the lives of the T2D patients.