Apr 4, 2020

Beta cell identity changes with mild hyperglycemia: Implications for function, growth, and vulnerability

Molecular Metabolism
Aref G EbrahimiGordon C Weir

Abstract

As diabetes develops, marked reductions of insulin secretion are associated with very modest elevations of glucose. We wondered if these glucose changes disrupt beta cell differentiation enough to account for the altered function. Rats were subjected to 90% partial pancreatectomies and those with only mild glucose elevations 4 weeks or 10 weeks after surgery had major alterations of gene expression in their islets as determined by RNAseq. Changes associated with glucose toxicity demonstrated that many of the critical genes responsible for insulin secretion were downregulated while the expression of normally suppressed genes increased. Also, there were marked changes in genes associated with replication, aging, senescence, stress, inflammation, and increased expression of genes controlling both class I and II MHC antigens. These findings suggest that mild glucose elevations in the early stages of diabetes lead to phenotypic changes that adversely affect beta cell function, growth, and vulnerability.

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Mentioned in this Paper

Genes
Insulin Secretion
Operative Surgical Procedures
Gene Expression
Stress
Structure of Beta Cell of Islet
Subtotal Pancreatectomy
Glucose
Histocompatibility Antigens Class II
Senescence Function

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