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).
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Department of Medicine, Diabetes Division, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229-3900, USA.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Guardado Mendoza
authors.forename: Carla
authors.initials: C
authors.lastname: Perego
authors.forename: Giovanna
authors.initials: G
authors.lastname: Finzi
authors.forename: Stefano
authors.initials: S
authors.lastname: La Rosa
authors.forename: Carlo
authors.initials: C
authors.lastname: Capella
authors.forename: Lilia M
authors.initials: LM
authors.lastname: Jimenez-Ceja
authors.forename: Licio A
authors.initials: LA
authors.lastname: Velloso
authors.forename: Mario J A
authors.initials: MJ
authors.lastname: Saad
authors.forename: Fausto
authors.initials: F
authors.lastname: Sessa
authors.forename: Federico
authors.initials: F
authors.lastname: Bertuzzi
authors.forename: Stefania
authors.initials: S
authors.lastname: Moretti
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Dick
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Davalli
authors.forename: Franco
authors.initials: F
authors.lastname: Folli
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D050416:Glucagon-Secreting Cells / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D008297:Male; D048529:Papio hamadryas; D019864:Somatostatin-Secreting Cells / Q000378:metabolism / Q000473:pathology*
chemical_list: D001786:Blood Glucose; D053148:Caspase 3