Authors: Rodolfo Guardado Mendoza Carla Perego Giovanna Finzi Stefano La Rosa Carlo Capella Lilia M JimenezCeja Licio A Velloso Mario J A Saad Fausto Sessa Federico Bertuzzi Stefania Moretti Edward J Dick Alberto M Davalli Franco Folli
Publish Date: 2015/06/07
Volume: 58, Issue: 8, Pages: 1814-1826
Abstract
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 valuesWe measured the volumes of alpha beta and delta cells and amyloid in pancreatic islets of 40 baboons Group 1 G1 FPG 444 mmol/l n = 10 G2 FPG = 444–526 mmol/l n = 9 G3 FPG = 527–694 mmol/l n = 9 G4 FPG 694 mmol/l n = 12 and correlated islet composition with metabolic and hormonal variables We also performed confocal microscopy including TUNEL caspase3 and anticaspase cleavage product of cytokeratin 18 M30 immunostaining electron microscopy and immunoelectron microscopy with antisomatostatin antibodies in baboon pancreasesAmyloidosis preceded the decrease in beta cell volume Alpha cell volume increased ∼50 in G3 and G4 p 005 while delta cell volume decreased in these groups by 31 and 39 respectively p 005 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 caspase3 and M30 showed apoptosis of beta and delta cells which was also confirmed by immunoelectron microscopy with antisomatostatin antibodiesIn 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
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