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

Research output: Contribution to journalArticle

44 Citations (Scopus)

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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Cell Dedifferentiation
Cell Degranulation
Medical problems
Type 2 Diabetes Mellitus
Cells
Endocrine Cells
Islets of Langerhans
Cell Transdifferentiation
Hormones
Pancreas
Exocrine Pancreas
Defects
Regeneration
Autopsy

ASJC Scopus subject areas

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

Cite this

α-Cell deficit in obese type 2 diabetes, a minor role of α-Cell dedifferentiation and degranulation. / Butler, Alexandra E.; Dhawan, Sangeeta; Hoang, Jonathan; Cory, Megan; Zeng, Kylie; Fritsch, Helga; Meier, Juris J.; Rizza, Robert A.; Butler, Peter C.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 101, No. 2, 01.02.2016, p. 523-532.

Research output: Contribution to journalArticle

Butler, AE, Dhawan, S, Hoang, J, Cory, M, Zeng, K, Fritsch, H, Meier, JJ, Rizza, RA & Butler, PC 2016, 'α-Cell deficit in obese type 2 diabetes, a minor role of α-Cell dedifferentiation and degranulation', Journal of Clinical Endocrinology and Metabolism, vol. 101, no. 2, pp. 523-532. https://doi.org/10.1210/jc.2015-3566
Butler, Alexandra E. ; Dhawan, Sangeeta ; Hoang, Jonathan ; Cory, Megan ; Zeng, Kylie ; Fritsch, Helga ; Meier, Juris J. ; Rizza, Robert A. ; Butler, Peter C. / α-Cell deficit in obese type 2 diabetes, a minor role of α-Cell dedifferentiation and degranulation. In: Journal of Clinical Endocrinology and Metabolism. 2016 ; Vol. 101, No. 2. pp. 523-532.
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