α-Cell deficit in obese type 2 diabetes, a minor role of α-Cell dedifferentiation and degranulation

Alexandra E. Butler, Sangeeta Dhawan, Jonathan Hoang, Megan Cory, Kylie Zeng, Helga Fritsch, Juris J. Meier, Robert A. Rizza, Peter C. Butler

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Abstract

Context: Type 2 diabetes is characterized by a α-Cell deficit and a progressive defect in α-Cell function. It has been proposed that the deficit in α-Cells may be due to α-Cell degranulation and transdifferentiation to other endocrine cell types. Objective: The objective of the study was to establish the potential impact of α-Cell dedifferentiation and transdifferentiation on α-Cell deficit in type 2 diabetes and to consider the alternative that cells with an incomplete identity may be newly forming rather than dedifferentiated. Design, Setting, and Participants: Pancreata obtained at autopsy were evaluated from 14 nondiabetic and 13 type 2 diabetic individuals, from four fetal cases, and from 10 neonatal cases. Results: Whereas there was a slight increase in islet endocrine cells expressing no hormone in type 2 diabetes (0.11 0.03 cells/islet vs 0.03 0.01 cells/islet, P <.01), the impact on the α-Cell deficit would be minimal. Furthermore, we established that the deficit in α-Cells per islet cannot be accounted for by an increase in other endocrine cell types. The distribution of hormone negative endocrine cells in type 2 diabetes (most abundant in cells scattered in the exocrine pancreas) mirrors that in developing (embryo and neonatal) pancreas, implying that these may represent newly forming cells. Conclusions: Therefore, although we concur that in type 2 diabetes there are endocrine cells with altered cell identity, this process does not account for the deficit in α-Cells in type 2 diabetes but may reflect, in part, attempted α-Cell regeneration.

Original languageEnglish (US)
Pages (from-to)523-532
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume101
Issue number2
DOIs
StatePublished - Feb 1 2016

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ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Butler, A. E., Dhawan, S., Hoang, J., Cory, M., Zeng, K., Fritsch, H., Meier, J. J., Rizza, R. A., & Butler, P. C. (2016). α-Cell deficit in obese type 2 diabetes, a minor role of α-Cell dedifferentiation and degranulation. Journal of Clinical Endocrinology and Metabolism, 101(2), 523-532. https://doi.org/10.1210/jc.2015-3566