Hydrogen Sulfide and Carbohydrate Metabolism

Hydrogen sulfide (H₂S) is an important gasotransmitter with diverse biological actions in the body and has been receiving much attention over the last two decades. It has been characterized as a key regulator of cardiovascular homoeostasis, cell growth and differentiation, mitochondrial biogenesis, adipose tissue metabolism, inflammation and liver function. H₂S-donor molecules have hence been considered as being potential therapeutic options for a variety of human diseases including hypertension, atherosclerosis, obesity, oxidative stress and chronic inflammation. It has been shown that huge amount of endogenous H₂S originates in the liver, and may be involved in the development of insulin resistance and diabetes. H₂S is considered as an important mediator of carbohydrate homeostasis. H₂S production and bioavailability are impaired during development of obesity, diabetes and its complications, highlights the potential therapeutic effects of H₂S in metabolic syndrome. This issue is however controversial due to some findings that show increased H₂S disturbs pancreatic β-cell function and may be responsible for reduced insulin secretion. H₂S also contributes to increased blood glucose levels by accelerating glycogenolysis and gluconeogenesis, effects which could intensify hyperglycemia in diabetes. Furthermore, reduced basal and insulin-stimulated glucose uptake was observed following treatment of adipocytes with H₂S; in contrast, the protective effect of H₂S on β-cell function against a high-fat diet, as well as its insulin-sensitizing properties has been reported in both in vitro and in vivo models of insulin resistance. Regarding the increasing interest in therapeutic applications of H₂S-donors in cardiometabolic disorders, its potential unexpected effects on glucose/insulin metabolism, especially in the case of diabetes, should be considered. In this review, we focus on the current knowledge available on exogenous and endogenous H₂S and carbohydrate metabolism, including both regulation of hepatic glucose production and hepatic and peripheral glucose uptake and β-cell function.

Keywords: Carbohydrate metabolism, Cystathionine γ lyase, Cystathionine β synthase, Diabetes, Glucose, Hydrogen sulfide, Insulin, Nitric oxide, Sodium sulfide, 3- mercaptopyruvate sulfurtransferase.