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

Publication date: 6 March 2018
Source:Cell Reports, Volume 22, Issue 10
Author(s): 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
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.

Graphical abstract

Teaser

Brissova et al. find that β cells in the type 1 diabetic (T1D) pancreas maintain several functional and molecular features, but α cells have impaired glucagon secretion and an altered gene expression profile. These findings provide insight into the mechanism of α cell dysfunction in T1D.


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