α Cell Function and Gene Expression Are Compromised in Type 1 Diabetes
Marcela Brissova, Rachana Haliyur, Diane Saunders, Shristi Shrestha, Chunhua Dai, David M Blodgett, Rita Bottino, Martha Campbell-Thompson, Radhika Aramandla, Gregory Poffenberger, Jill Lindner, Fong Cheng Pan, Matthias G von Herrath, Dale L Greiner, Leonard D Shultz, May Sanyoura, Louis H Philipson, Mark Atkinson, David M Harlan, Shawn E Levy, Nripesh Prasad, Roland Stein, Alvin C Powers, Marcela Brissova, Rachana Haliyur, Diane Saunders, Shristi Shrestha, Chunhua Dai, David M Blodgett, Rita Bottino, Martha Campbell-Thompson, Radhika Aramandla, Gregory Poffenberger, Jill Lindner, Fong Cheng Pan, Matthias G von Herrath, Dale L Greiner, Leonard D Shultz, May Sanyoura, Louis H Philipson, Mark Atkinson, David M Harlan, Shawn E Levy, Nripesh Prasad, Roland Stein, Alvin C Powers
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.
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
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References
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