51. β-Cell Deficit in Obese Type 2 Diabetes, a Minor Role of β-Cell Dedifferentiation and Degranulation
- Author
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Butler, Alexandra E, Dhawan, Sangeeta, Hoang, Jonathan, Cory, Megan, Zeng, Kylie, Fritsch, Helga, Meier, Juris J, Rizza, Robert A, and Butler, Peter C
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Pediatric ,Autoimmune Disease ,Regenerative Medicine ,Diabetes ,Metabolic and endocrine ,Age Factors ,Aged ,Autopsy ,Body Mass Index ,Cell Dedifferentiation ,Cell Degranulation ,Diabetes Mellitus ,Type 2 ,Humans ,Infant ,Newborn ,Insulin-Secreting Cells ,Middle Aged ,Obesity ,Pancreas ,Paediatrics and Reproductive Medicine ,Endocrinology & Metabolism ,Clinical sciences - Abstract
ContextType 2 diabetes is characterized by a β-cell deficit and a progressive defect in β-cell function. It has been proposed that the deficit in β-cells may be due to β-cell degranulation and transdifferentiation to other endocrine cell types.ObjectiveThe objective of the study was to establish the potential impact of β-cell dedifferentiation and transdifferentiation on β-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 participantsPancreata obtained at autopsy were evaluated from 14 nondiabetic and 13 type 2 diabetic individuals, from four fetal cases, and from 10 neonatal cases.ResultsWhereas 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 β-cell deficit would be minimal. Furthermore, we established that the deficit in β-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.ConclusionsTherefore, 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 β-cells in type 2 diabetes but may reflect, in part, attempted β-cell regeneration.
- Published
- 2016