Department of Medicine, Diabetes Division, Diabetes Center of Excellence
Cell Biology | Cellular and Molecular Physiology | Endocrine System Diseases | Endocrinology | Genetic Phenomena | Hormones, Hormone Substitutes, and Hormone Antagonists | Immune System Diseases | Nutritional and Metabolic Diseases
Many patients with type 1 diabetes (T1D) have residual beta cells producing small amounts of C-peptide long after disease onset but develop an inadequate glucagon response to hypoglycemia following T1D diagnosis. The features of these residual beta cells and alpha cells in the islet endocrine compartment are largely unknown, due to the difficulty of comprehensive investigation. By studying the T1D pancreas and isolated islets, we show that remnant beta cells appeared to maintain several aspects of regulated insulin secretion. However, the function of T1D alpha cells was markedly reduced, and these cells had alterations in transcription factors constituting alpha and beta cell identity. In the native pancreas and after placing the T1D islets into a non-autoimmune, normoglycemic in vivo environment, there was no evidence of alpha-to-beta cell conversion. These results suggest an explanation for the disordered T1D counterregulatory glucagon response to hypoglycemia.
alpha cells, glucagon, human, insulin, pancreatic islet, type 1 diabetes
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© 2018 The Authors. Under a Creative Commons license: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
DOI of Published Version
Cell Rep. 2018 Mar 6;22(10):2667-2676. doi: 10.1016/j.celrep.2018.02.032. Link to article on publisher's site
Brissova, Marcela; Blodgett, David; Greiner, Dale L.; Harlan, David M.; and Powers, Alvin C., "alpha Cell Function and Gene Expression Are Compromised in Type 1 Diabetes" (2018). Open Access Articles. 3413.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Cell Biology Commons, Cellular and Molecular Physiology Commons, Endocrine System Diseases Commons, Endocrinology Commons, Genetic Phenomena Commons, Hormones, Hormone Substitutes, and Hormone Antagonists Commons, Immune System Diseases Commons, Nutritional and Metabolic Diseases Commons