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

Autor:	Brissova M; Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: marcela.brissova@vanderbilt.edu., Haliyur R; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA., Saunders D; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA., Shrestha S; HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA., Dai C; Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA., Blodgett DM; 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., Bottino R; Institute of Cellular Therapeutics, Allegheny-Singer Research Institute, Allegheny Health Network, Pittsburgh, PA, USA., Campbell-Thompson M; Department of Pathology, University of Florida Diabetes Institute, College of Medicine, Gainesville, FL, USA., Aramandla R; Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA., Poffenberger G; Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA., Lindner J; Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA., Pan FC; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA., von Herrath MG; Type 1 Diabetes Center, the La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA., Greiner DL; Department of Medicine, Diabetes Division, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USA., Shultz LD; The Jackson Laboratory, Bar Harbor, ME, USA., Sanyoura M; Departments of Medicine and Pediatrics, Section of Endocrinology, Diabetes, and Metabolism, University of Chicago, Chicago, IL, USA., Philipson LH; Departments of Medicine and Pediatrics, Section of Endocrinology, Diabetes, and Metabolism, University of Chicago, Chicago, IL, USA., Atkinson M; Department of Pathology, University of Florida Diabetes Institute, College of Medicine, Gainesville, FL, USA., Harlan DM; Department of Medicine, Diabetes Division, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USA., Levy SE; HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA., Prasad N; HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA., Stein R; 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., Powers AC; 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.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2018 Mar 06; Vol. 22 (10), pp. 2667-2676.
DOI:	10.1016/j.celrep.2018.02.032
Abstrakt:	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. (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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