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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Diabetologia
2015 ; 58
(8
): 1814-26
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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)
#MMPMID26049399
Guardado Mendoza R
; Perego C
; Finzi G
; La Rosa S
; Capella C
; Jimenez-Ceja LM
; Velloso LA
; Saad MJ
; Sessa F
; Bertuzzi F
; Moretti S
; Dick EJ Jr
; Davalli AM
; Folli F
Diabetologia
2015[Aug]; 58
(8
): 1814-26
PMID26049399
show ga
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.
|*Cell Death
[MESH]
|Animals
[MESH]
|Blood Glucose/metabolism
[MESH]
|Caspase 3/metabolism
[MESH]
|Diabetes Mellitus, Type 2/metabolism/*pathology
[MESH]