Delta cell death in the islet of Langerhans and the progression from normal glucose tolerance to type 2 diabetes in non-human primates (baboon, Papio hamadryas).

Details

Serval ID
serval:BIB_AC7247BD9C32
Type
Article: article from journal or magazin.
Collection
Publications
Title
Delta cell death in the islet of Langerhans and the progression from normal glucose tolerance to type 2 diabetes in non-human primates (baboon, Papio hamadryas).
Journal
Diabetologia
Author(s)
Guardado Mendoza R., Perego C., Finzi G., La Rosa S., Capella C., Jimenez-Ceja L.M., Velloso L.A., Saad M.J., Sessa F., Bertuzzi F., Moretti S., Dick E.J., Davalli A.M., Folli F.
ISSN
1432-0428 (Electronic)
ISSN-L
0012-186X
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
58
Number
8
Pages
1814-1826
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
AIMS/HYPOTHESIS: The cellular composition of the islet of Langerhans is essential to ensure its physiological function. Morphophysiological islet abnormalities are present in type 2 diabetes but the relationship between fasting plasma glucose (FPG) and islet cell composition, particularly the role of delta cells, is unknown. We explored these questions in pancreases from baboons (Papio hamadryas) with FPG ranging from normal to type 2 diabetic values.
METHODS: We measured the volumes of alpha, beta and delta cells and amyloid in pancreatic islets of 40 baboons (Group 1 [G1]: FPG < 4.44 mmol/l [n = 10]; G2: FPG = 4.44-5.26 mmol/l [n = 9]; G3: FPG = 5.27-6.94 mmol/l [n = 9]; G4: FPG > 6.94 mmol/l [n = 12]) and correlated islet composition with metabolic and hormonal variables. We also performed confocal microscopy including TUNEL, caspase-3, and anti-caspase cleavage product of cytokeratin 18 (M30) immunostaining, electron microscopy, and immuno-electron microscopy with anti-somatostatin antibodies in baboon pancreases.
RESULTS: Amyloidosis preceded the decrease in beta cell volume. Alpha cell volume increased ∼ 50% in G3 and G4 (p < 0.05), while delta cell volume decreased in these groups by 31% and 39%, respectively (p < 0.05). In G4, glucagon levels were higher, while insulin and HOMA index of beta cell function were lower than in the other groups. Immunostaining of G4 pancreatic sections with TUNEL, caspase-3 and M30 showed apoptosis of beta and delta cells, which was also confirmed by immuno-electron microscopy with anti-somatostatin antibodies.
CONCLUSIONS/INTERPRETATION: In diabetic baboons, changes in islet composition correlate with amyloid deposition, with increased alpha cell and decreased beta and delta cell volume and number due to apoptosis. These data argue for an important role of delta cells in type 2 diabetes.
Keywords
Animals, Blood Glucose/metabolism, Caspase 3/metabolism, Cell Death, Diabetes Mellitus, Type 2/metabolism, Diabetes Mellitus, Type 2/pathology, Disease Progression, Female, Glucagon-Secreting Cells/metabolism, Glucagon-Secreting Cells/pathology, Insulin Resistance/physiology, Insulin-Secreting Cells/metabolism, Insulin-Secreting Cells/pathology, Islets of Langerhans/metabolism, Islets of Langerhans/pathology, Male, Papio hamadryas, Somatostatin-Secreting Cells/metabolism, Somatostatin-Secreting Cells/pathology
Pubmed
Web of science
Open Access
Yes
Create date
06/09/2016 11:50
Last modification date
20/08/2019 15:16
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