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

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...

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Vydané v:	Cell reports (Cambridge) Ročník 22; číslo 10; s. 2667 - 2676
Hlavní autori:	Brissova, Marcela, Haliyur, Rachana, Saunders, Diane, Shrestha, Shristi, Dai, Chunhua, Blodgett, David M., Bottino, Rita, Campbell-Thompson, Martha, Aramandla, Radhika, Poffenberger, Gregory, Lindner, Jill, Pan, Fong Cheng, von Herrath, Matthias G., Greiner, Dale L., Shultz, Leonard D., Sanyoura, May, Philipson, Louis H., Atkinson, Mark, Harlan, David M., Levy, Shawn E., Prasad, Nripesh, Stein, Roland, Powers, Alvin C.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Elsevier Inc 06.03.2018 Elsevier
Predmet:	Adolescent Adult alpha cells Animals Case-Control Studies Cellular Reprogramming Child Diabetes Mellitus, Type 1 - genetics Female Gene Expression Regulation glucagon Glucagon - metabolism Glucagon-Secreting Cells - metabolism Glucagon-Secreting Cells - pathology human Humans insulin Insulin Secretion Insulin-Secreting Cells - metabolism Insulin-Secreting Cells - pathology Male Mice Middle Aged pancreatic islet Phenotype Tissue Donors Transcription Factors - metabolism type 1 diabetes Young Adult glucagon type 1 diabetes pancreatic islet insulin human alpha cells
ISSN:	2211-1247, 2211-1247
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Popis
Shrnutí:	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. [Display omitted] •T1D β cells appear to maintain several aspects of regulated insulin secretion•T1D α cells have impaired glucagon secretion and altered gene expression•Unlike in rodents, α-to-β cell conversion in human T1D is a very rare event•T1D α cell identity factors improve in a non-autoimmune, normoglycemic environment 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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Lead Contact These authors contributed equally
ISSN:	2211-1247 2211-1247
DOI:	10.1016/j.celrep.2018.02.032