Bitoin does not directly act in the mechanism of arginine-induced insulin secretion

Abstract

Insulin secretion is regulated by a number of factors, including a rise in a ATP/ADP ratio, cAMP production and plasma membrane depolarization, leading to a increase in intracellular Ca²⁺ ([Ca²⁺]i). Arginine, like glucose, is a well-known insulin secretagogue. It is recognized that arginine stimulates insulin secretion by a membrane depolarization with their positive charge. As another possible mechanism, it is proposed that arginine enhances a nitric oxide (NO) productions as its metabolites, which can activate several pathways and increase [Ca²⁺]i. Our previous study indicates that biotin directly acts in the glucose metabolic pathway for ATP production and modulates glucose-induced insulin secretion. But, it remains to clear whether biotin acts as a regulator of arginine-induced insulin secretion. We studied the effect of biotin deficiency on arginine-induced insulin secretion by isolated pancreas perfusion of rats. Insulin secretion was stimulated with l-arginine, n-nitro-l-arginine-methyl ester (l-NAME) which does not work as an NO-donor for NO production, and d-arginine which is not metabolized in the mammalian cells. In the moderate biotin deficient rats, the level of insulin response was significantly lower than that in the control rats only when insulin was stimulated with d-arginine. In the sever biotin deficient rats, insulin secretions stimulated with each of every secretagogues markedly diminished. These results indicate that arginine-induced insulin secretion was actually impaired by biotin deficiency, but biotin did not directly act as a regulator of arginine-induced insulin secretion. It may be caused by a histologic dysfunction in pancreatic β cells by biotin deficiency.