UMMS Affiliation

Department of Medicine, Diabetes Division, Diabetes Center of Excellence

Publication Date

2018-03-06

Document Type

Article

Disciplines

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

Abstract

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.

Keywords

alpha cells, glucagon, human, insulin, pancreatic islet, type 1 diabetes

Rights and Permissions

© 2018 The Authors. Under a Creative Commons license: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

DOI of Published Version

10.1016/j.celrep.2018.02.032

Source

Cell Rep. 2018 Mar 6;22(10):2667-2676. doi: 10.1016/j.celrep.2018.02.032. Link to article on publisher's site

Journal/Book/Conference Title

Cell reports

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

29514095

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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