Islet amyloid formation associated with hyperglycemia in transgenic mice with pancreatic beta cell expression of human islet amyloid polypeptide

Pancreatic islet amyloid deposits are a characteristic pathologic feature of non-insulin-dependent diabetes mellitus and contain islet amyloid polypeptide (IAPP: amylin). We used transgenic mice that express human IAPP in pancreatic beta cells to explore the potential role of islet amyloid in the pa...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1996-04, Vol.93 (8), p.3492-3496
Main Authors: Verchere, C. Bruce, D'Alessio, David A., Palmiter, Richard D., Weir, Gordon C., Bonner-Weir, Susan, Baskin, Denis G., Kahn, Steven E.
Format: Article
Language:English
Subjects:
Amyloid - genetics
Amyloid - metabolism
Amyloid plaque
Amyloids
animal transgenique
animales transgenicos
Animals
Biochemistry
Blood plasma
diabete
Diabetes
Diabetes Mellitus, Type 2 - etiology
Diabetes Mellitus, Type 2 - genetics
Diabetes Mellitus, Type 2 - metabolism
Disease Models, Animal
Female
Gene Expression
genero humano
genre humain
glicoproteinas
glycoproteine
glycoproteins
hiperglicemia
Humans
hyperglycaemia
Hyperglycemia
Hyperglycemia - genetics
Hyperglycemia - metabolism
hyperglycemie
Insulin
Insulin - blood
insulina
insuline
Islet Amyloid Polypeptide
Islets of Langerhans - metabolism
Islets of Langerhans - ultrastructure
Male
mankind
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Transgenic
Microscopy, Immunoelectron
pancreas
peptide
peptides
peptidos
raton
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Rodents
Solar fibrils
souris
Transgenic animals
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Summary:Pancreatic islet amyloid deposits are a characteristic pathologic feature of non-insulin-dependent diabetes mellitus and contain islet amyloid polypeptide (IAPP: amylin). We used transgenic mice that express human IAPP in pancreatic beta cells to explore the potential role of islet amyloid in the pathogenesis of non-insulin-dependent diabetes mellitus. Extensive amyloid deposits were observed in the pancreatic islets of approximately 80% of male transgenic mice > 13 months of age. Islet amyloid deposits were rarely observed in female transgenic mice (11%) and were never seen in nontransgenic animals. Ultrastructural analysis revealed that these deposits were composed of human IAPP-immunoreactive fibrils that accumulated between beta cells and islet capillaries. Strikingly, approximately half of the mice with islet amyloid deposits were hyperglycemic (plasma glucose > 11 mM). In younger (6-to 9-month-old) male transgenic mice, islet amyloid deposits were less commonly observed but were always associated with severe hyperglycemia (plasma glucose > 22 mM). These data indicate that expression of human IAPP in beta cells predisposes male mice to the development of islet amyloid and hyperglycemia. The frequent concordance of islet amyloid with hyperglycemia in these mice suggests an interdependence of these two conditions and supports the hypothesis that islet amyloid may play a role in the development of hyperglycemia.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.93.8.3492