Metabolic effects of L-citrulline in type 2 diabetes.

2023-01-25
Acta physiologica (Oxford, England) 237(3)
- Fatemeh Bagheripour
- Sajad Jeddi
- Khosrow Kashfi
- Asghar Ghasemi

PubMed: 36645144
DOI: 10.1111/apha.13937

Study Design

Type: Review

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 β cells, increased glucose uptake by the skeletal muscle, as well as increased lipolysis and β-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.

Research Insights

L-Citrulline→Improved Dyslipidemia
Cit supplementation in T2D increases circulating levels of Cit and L-arginine while decreasing circulating glucose and free fatty acids and improving dyslipidemia.
Effect
Beneficial
Effect size
Small
L-Citrulline→Increased Beta-Oxidation
The underlying mechanisms for these beneficial effects of Cit include increased insulin secretion from the pancreatic β cells, increased glucose uptake by the skeletal muscle, as well as increased lipolysis and β-oxidation, and decreased glyceroneogenesis in the adipose tissue.
Effect
Beneficial
Effect size
Small
L-Citrulline→Increased Glucose Uptake
The underlying mechanisms for these beneficial effects of Cit include increased insulin secretion from the pancreatic β cells, increased glucose uptake by the skeletal muscle, as well as increased lipolysis and β-oxidation, and decreased glyceroneogenesis in the adipose tissue.
Effect
Beneficial
Effect size
Small
L-Citrulline→Increased Insulin Secretion
The underlying mechanisms for these beneficial effects of Cit include increased insulin secretion from the pancreatic β cells, increased glucose uptake by the skeletal muscle, as well as increased lipolysis and β-oxidation, and decreased glyceroneogenesis in the adipose tissue.
Effect
Beneficial
Effect size
Small
L-Citrulline→Increased Lipolysis
The underlying mechanisms for these beneficial effects of Cit include increased insulin secretion from the pancreatic β cells, increased glucose uptake by the skeletal muscle, as well as increased lipolysis and β-oxidation, and decreased glyceroneogenesis in the adipose tissue.
Effect
Beneficial
Effect size
Small
L-Citrulline→Reduced Blood Glucose Level
Cit supplementation in T2D increases circulating levels of Cit and L-arginine while decreasing circulating glucose and free fatty acids and improving dyslipidemia.
Effect
Beneficial
Effect size
Small
L-Citrulline→Reduced Free Fatty Acid Level
Cit supplementation in T2D increases circulating levels of Cit and L-arginine while decreasing circulating glucose and free fatty acids and improving dyslipidemia.
Effect
Beneficial
Effect size
Small
L-Citrulline→Reduced Glyceroneogenesis
The underlying mechanisms for these beneficial effects of Cit include increased insulin secretion from the pancreatic β cells, increased glucose uptake by the skeletal muscle, as well as increased lipolysis and β-oxidation, and decreased glyceroneogenesis in the adipose tissue.
Effect
Beneficial
Effect size
Small