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Therapeutic Use of Glucagon: The Future of Diabetes Mellitus Therapy

Norikiyo Honzawa, Kei Fujimoto* (JAPAN)

Category: Endocrinology

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The etiology of type 2 diabetes has long been centered on insulin. Recently, however, glucagon has been attracting attention. It has been reported that glucagon receptor or pancreatic α cell-deficient mice do not deteriorate glucose intolerance after pancreatic beta cells are destroyed with streptozotocin and insulin secretion is depleted. This suggests that glucagon and glucagon receptors are crucial for glucose intolerance in diabetes mellitus, and the elucidation of glucagon signaling is still awaited. This review will begin with an overview of the history of glucagon. In the nearly 100 years since the discovery of glucagon, it has become clear that glucagon plays a role in blood glucose in type 2 diabetes as much or more than insulin. This is due in large part to the advent of the sándwich Enzyme-Linked Immunosorbent Assay (ELISA) method, which allows accurate measurement of glucagon by using N- and C-terminal antibodies. Next, the mechanism of action of glucagon on blood glucose levels will be outlined. Glucagon increases blood glucose levels by enhancing gluconeogenesis and glycogenolysis. Glucagon also enhances lipolysis, which indirectly contributes to weight loss and improved blood glucose levels. Recently, mice with defective or decreased glucagon secretion have been developed, and the effects of glucagon are becoming clearer in vivo. Mice with elevated glucagon secretion have also appeared, and their glucose tolerance improvement through lipolysis and weight loss is also attracting attention. Research on glucagon is not limited to animal experiments but has already reached the stage of clinical application. Drugs that suppress glucagon have side effects such as liver damage, but they are effective in improving blood glucose. Drugs that increase glucagon also have hypoglycemic effects resulting from weight loss. Thus, glucagon has undergone a dizzying evolution over the past decade. The day may soon come when drugs that target glucagon will dominate diabetes treatment.

Keywords: Blood Glucose, Glucagon, Type 2 Diabetes Mellitus , Pancreatic Alpha Cell


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DOI: 10.55828/ijcicr-13-13