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

Year: 2018

Type: article

Abstract: Many patients with type 1 diabetes (T1D) have residual beta 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 beta cells and alpha 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 beta cells appeared to maintain several aspects of regulated insulin secretion. However, the function of T1D alpha cells was markedly reduced, and these cells had alterations in transcription factors constituting alpha and beta 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 alpha-to-beta cell conversion. These results suggest an explanation for the disordered T1D counterregulatory glucagon response to hypoglycemia.

Source: The Journal of the American Medical Association (JAMA) Network (American Medical Association)

Authors: Brissova, Marcela, Blodgett, David, Greiner, Dale L., Harlan, David M., Powers, Alvin C.

Institutions: University of Massachusetts Chan Medical School, Babson College

Language: English

Topic: Pancreatic function and diabetes

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: U.S. Department of Veterans Affairs, Vanderbilt University, Leona M. and Harry B. Helmsley Charitable Trust, Human Islet Research Network, Vanderbilt Diabetes Research and Training Center, Vanderbilt University Medical Center, National Institute of Diabetes and Digestive and Kidney Diseases

OpenAlex ID: W7017098537