Role of Protein Kinase C in Insulin Resistance and Metabolic Syndrome

One mechanism contributing to insulin resistance is the serine/threonine phosphorylation of critical proteins involved in insulin signaling, particularly the insulin receptor, its downstream substrates, and the activation of protein tyrosine phosphatases. These modifications are associated with decreased insulin signaling, leading to insulin resistance. Protein kinase C (PKC), a family of serine/threonine kinases activated by lipids and/or Ca2+, is essential for regulating metabolism and maintaining cellular homeostasis. These kinases regulate glucose uptake and lipid storage, thereby influencing energy balance through tissue-specific mechanisms. However, dysregulation of PKC activity is closely associated with the development of metabolic syndrome (MetS), a cluster of interconnected physiological and biochemical alterations, including insulin resistance, lipid dysregulation, chronic inflammation, hypertension, and obesity, all of which increase the risk of cardiovascular disease (CVD) and type 2 diabetes (T2D). Notably, alterations in PKC signaling can impair insulin’s ability to facilitate glucose uptake and storage and disrupt lipid storage mechanisms, thereby exacerbating insulin resistance. These dysfunctions significantly contribute to the pathophysiology of MetS. This review aims to examine PKC activation under normal physiological conditions, with particular emphasis on its role in insulin signaling, and to explore how PKC dysregulation participates in the pathophysiology of insulin resistance and MetS.