Pancreatic islet amyloidosis, beta-cell apoptosis, and alpha-cell proliferation are determinants of islet remodeling in type-2 diabetic baboons.

Détails

ID Serval
serval:BIB_D12A40447395
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Pancreatic islet amyloidosis, beta-cell apoptosis, and alpha-cell proliferation are determinants of islet remodeling in type-2 diabetic baboons.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Guardado-Mendoza R., Davalli A.M., Chavez A.O., Hubbard G.B., Dick E.J., Majluf-Cruz A., Tene-Perez C.E., Goldschmidt L., Hart J., Perego C., Comuzzie A.G., Tejero M.E., Finzi G., Placidi C., La Rosa S., Capella C., Halff G., Gastaldelli A., DeFronzo R.A., Folli F.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
106
Numéro
33
Pages
13992-13997
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
beta-Cell dysfunction is an important factor in the development of hyperglycemia of type-2 diabetes mellitus, and pancreatic islet amyloidosis (IA) has been postulated to be one of the main contributors to impaired insulin secretion. The aim of this study was to evaluate the correlation of IA with metabolic parameters and its effect on islets of Langerhans remodeling and relative endocrine-cell volume in baboons. We sequenced the amylin peptide, determined the fibrillogenic propensities, and evaluated pancreatic histology, clinical and biochemical characteristics, and endocrine cell proliferation and apoptosis in 150 baboons with different metabolic status. Amylin sequence in the baboon was 92% similar to humans and showed superimposable fibrillogenic propensities. IA severity correlated with fasting plasma glucose (FPG) (r = 0.662, P < 0.001) and HbA1c (r = 0.726, P < 0.001), as well as with free fatty acid, glucagon values, decreased homeostasis model assessment (HOMA) insulin resistance, and HOMA-B. IA severity was associated with a decreased relative beta-cell volume, and increased relative alpha-cell volume and hyperglucagonemia. These results strongly support the concept that IA and beta-cell apoptosis in concert with alpha-cell proliferation and hypertrophy are key determinants of islets of Langerhans "dysfunctional remodeling" and hyperglycemia in the baboon, a nonhuman primate model of type-2 diabetes mellitus. The most important determinants of IA were age and FPG (R(2) = 0.519, P < 0.0001), and different FPG levels were sensitive and specific to predict IA severity. Finally, a predictive model for islet amyloid severity was generated with age and FPG as required variables.
Mots-clé
Amyloid/metabolism, Amyloidosis/pathology, Animals, Apoptosis, Blood Glucose/metabolism, Diabetes Mellitus, Experimental/metabolism, Diabetes Mellitus, Experimental/pathology, Diabetes Mellitus, Type 2/metabolism, Diabetes Mellitus, Type 2/pathology, Fatty Acids/metabolism, Female, Glucagon-Secreting Cells/metabolism, Insulin Resistance, Insulin-Secreting Cells/metabolism, Islet Amyloid Polypeptide, Islets of Langerhans/pathology, Male, Papio
Pubmed
Web of science
Open Access
Oui
Création de la notice
06/09/2016 13:56
Dernière modification de la notice
20/08/2019 15:51
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