Metabolic effects of L-citrulline in type 2 diabetes

The prevalence of type 2 diabetes (T2D) is increasing worldwide. Decreased nitric oxide (NO) bioavailability is involved in the pathophysiology of T2D and its complications. L-citrulline (Cit), a precursor of NO production, has been suggested as a novel therapeutic agent for T2D. Available data from human and animal studies indicate that Cit supplementation in T2D increases circulating levels of Cit and L-arginine while decreasing circulating glucose and free fatty acids and improving dyslipidemia. The underlying mechanisms for these beneficial effects of Cit include increased insulin secretion from the pancreatic beta cells, increased glucose uptake by the skeletal muscle, as well as increased lipolysis and beta-oxidation, and decreased glyceroneogenesis in the adipose tissue. Thus, Cit has antihyperglycemic, antidyslipidemic, and antioxidant effects and has the potential to be used as a new therapeutic agent in the management of T2D. This review summarizes available literature from human and animal studies to explore the effects of Cit on metabolic parameters in T2D. It also discusses the possible mechanisms underlying Cit-induced improved metabolic parameters in T2D.

Automated summary

The prevalence of type 2 diabetes (T2D) is increasing worldwide. L-citrulline (Cit), a precursor of nitric oxide (NO) production, has been suggested as a potential therapeutic agent for T2D. Cit supplementation in T2D has shown positive effects on glucose, lipid, and antioxidant metabolism through multiple mechanisms, including increased insulin secretion, glucose uptake, lipolysis, and decreased glyceroneogenesis.