The alpha-cell in diabetes mellitus

摘要

Findings from the past 10 years have placed the glucagon-secreting pancreatic alpha-cell centre stage in the development of diabetes mellitus, a disease affecting almost one in every ten adults worldwide. Glucagon secretion is reduced in patients with type 1 diabetes mellitus, increasing the risk of insulin-induced hypoglycaemia, but is enhanced in type 2 diabetes mellitus, exacerbating the effects of diminished insulin release and action on blood levels of glucose. A better understanding of the mechanisms underlying these changes is therefore an important goal. RNA sequencing reveals that, despite their opposing roles in the control of blood levels of glucose, alpha-cells and beta-cells have remarkably similar patterns of gene expression. This similarity might explain the fairly facile interconversion between these cells and the ability of the alpha-cell compartment to serve as a source of new beta-cells in models of extreme beta-cell loss that mimic type 1 diabetes mellitus. Emerging data suggest that GABA might facilitate this interconversion, whereas the amino acid glutamine serves as a liver-derived factor to promote alpha-cell replication and maintenance of alpha-cell mass. Here, we survey these developments and their therapeutic implications for patients with diabetes mellitus.