Hydrogen sulfide regulates insulin secretion and insulin resistance in diabetes mellitus, a new promising target for diabetes mellitus treatment? A review

BACKGROUND: Insulin resistance and impaired insulin secretion lead to disorders of glucose metabolism, which contributes to the development of diabetes. Hydrogen sulfide (H2S), a novel gasotransmitter, is found to play important roles in regulation of glucose metabolism homeostasis. AIM OF REVIEW: This study aimed to summarize and discuss current data about the function of H2S in insulin secretion and insulin resistance regulation as well as the underlying mechanisms. KEY SCIENTIFIC CONCEPTS OF REVIEW: H(2)S could be endogenously produced in islet β cells, liver, adipose, skeletal muscles, and the hypothalamus, and regulates local and systemic glucose metabolism. It is reported that H(2)S suppresses insulin secretion, promotes or reduces the apoptosis of islet β cells. It plays important roles in the regulation of insulin sensitivity in insulin responsive tissues. H(2)S inhibits glucose uptake and glycogen storage, and promotes or inhibits gluconeogenesis, mitochondrial biogenesis and mitochondrial bioenergetics in the liver. In adipose tissue, several investigators indicated that H2S promoted glucose uptake in adipocytes, while other studies reported that H(2)S inhibits this process. H(2)S has also been shown to promote adipogenesis, inhibit lipolysis, and regulate adiponectin and MCP-1 secretion from adipocytes. In skeletal muscle, H(2)S increases glucose uptake and improves insulin sensitivity. It is also observed that H(2)S modulates circadian-clock genes in muscle. Hypothalamic CBS/H(2)S pathway reduces obesity and improves insulin sensitivity via the brain-adipose interaction. Most studies indicated plasma H(2)S levels decreased in diabetic patients. However, the mechanisms by which H(2)S regulates systemic glucose metabolism remain unclear. Whether H(2)S acts as a new promising target for diabetes mellitus treatment merits further studies.