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- Title
Normal and defective pathways in biogenesis and maintenance of the insulin storage pool.
- Authors
Ming Liu; Yumeng Huang; Xiaoxi Xu; Xin Li; Alam, Maroof; Arunagiri, Anoop; Haataja, Leena; Li Ding; Shusen Wang; Itkin-Ansari, Pamela; Kaufman, Randal J.; Tsai, Billy; Ling Qi; Arvan, Peter; Liu, Ming; Huang, Yumeng; Xu, Xiaoxi; Li, Xin; Ding, Li; Wang, Shusen
- Abstract
Both basal and glucose-stimulated insulin release occur primarily by insulin secretory granule exocytosis from pancreatic β cells, and both are needed to maintain normoglycemia. Loss of insulin-secreting β cells, accompanied by abnormal glucose tolerance, may involve simple exhaustion of insulin reserves (which, by immunostaining, appears as a loss of β cell identity), or β cell dedifferentiation, or β cell death. While various sensing and signaling defects can result in diminished insulin secretion, somewhat less attention has been paid to diabetes risk caused by insufficiency in the biosynthetic generation and maintenance of the total insulin granule storage pool. This Review offers an overview of insulin biosynthesis, beginning with the preproinsulin mRNA (translation and translocation into the ER), proinsulin folding and export from the ER, and delivery via the Golgi complex to secretory granules for conversion to insulin and ultimate hormone storage. All of these steps are needed for generation and maintenance of the total insulin granule pool, and defects in any of these steps may, weakly or strongly, perturb glycemic control. The foregoing considerations have obvious potential relevance to the pathogenesis of type 2 diabetes and some forms of monogenic diabetes; conceivably, several of these concepts might also have implications for β cell failure in type 1 diabetes.
- Subjects
INSULIN; TYPE 1 diabetes; GOLGI apparatus; SECRETORY granules; TYPE 2 diabetes
- Publication
Journal of Clinical Investigation, 2021, Vol 131, Issue 2, p1
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI142240