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Cell Rep. 2018 Mar 6;22(10):2667-2676. doi: 10.1016/j.celrep.2018.02.032.

α Cell Function and Gene Expression Are Compromised in Type 1 Diabetes.

Author information

1
Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: marcela.brissova@vanderbilt.edu.
2
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
3
HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
4
Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA.
5
Department of Medicine, Diabetes Division, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USA; Math and Science Division, Babson College, Wellesley, MA 02457, USA.
6
Institute of Cellular Therapeutics, Allegheny-Singer Research Institute, Allegheny Health Network, Pittsburgh, PA, USA.
7
Department of Pathology, University of Florida Diabetes Institute, College of Medicine, Gainesville, FL, USA.
8
Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.
9
Type 1 Diabetes Center, the La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
10
Department of Medicine, Diabetes Division, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USA.
11
The Jackson Laboratory, Bar Harbor, ME, USA.
12
Departments of Medicine and Pediatrics, Section of Endocrinology, Diabetes, and Metabolism, University of Chicago, Chicago, IL, USA.
13
Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.
14
Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA; Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA. Electronic address: al.powers@vanderbilt.edu.

Abstract

Many patients with type 1 diabetes (T1D) have residual β 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 β cells and α 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 β cells appeared to maintain several aspects of regulated insulin secretion. However, the function of T1D α cells was markedly reduced, and these cells had alterations in transcription factors constituting α and β 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 α-to-β 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

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