+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Islet amyloid-associated diabetes in obese A(vy)/a mice expressing human islet amyloid polypeptide



Islet amyloid-associated diabetes in obese A(vy)/a mice expressing human islet amyloid polypeptide



Diabetes 47(5): 743-750



We have previously shown that hemizygous transgenic mice expressing human islet amyloid polypeptide (hIAPP) in pancreatic beta-cells have no diabetic phenotype, whereas in the homozygous state, they developed severe, early-onset hyperglycemia associated with impaired insulin secretion and beta-cell death. We investigated the possibility that when the hemizygous mice are crossed onto an obese, insulin-resistant strain such as agouti viable yellow (A(vy)/a), they would exhibit a phenotype more akin to human type 2 diabetes. The hIAPP-expressing A(vy) males (TG-Y) displayed fasting hyperglycemia at 90 days of age and by 1 year progressed to severe hyperglycemia relative to their nontransgenic counterparts. Plasma insulin concentrations and pancreatic insulin content dropped 10- to 20-fold, suggesting severe impairment of beta-cell function. Histopathological findings revealed beta-cell degeneration and loss consistent with the drop in the plasma insulin concentration. In addition, large deposits of IAPP amyloid were present in TG-Y islets. We conclude that in transgenic mice expressing hIAPP, insulin resistance can induce overt, slow-onset diabetes associated with islet amyloid and decreased beta-cell mass.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 008922270

Download citation: RISBibTeXText

PMID: 9588445

DOI: 10.2337/diabetes.47.5.743


Related references

Formation of islet amyloid in pancreatic islets from transgenic mice expressing human islet amyloid polypeptide. Clinical Science 87(1): 39P, 1994

Formation of islet amyloid fibrils in beta-secretory granules of transgenic mice expressing human islet amyloid polypeptide/amylin. European Journal of Endocrinology 132(4): 487-496, 1995

Long-term treatment with rosiglitazone and metformin reduces the extent of, but does not prevent, islet amyloid deposition in mice expressing the gene for human islet amyloid polypeptide. Diabetes 54(7): 2235-2244, 2005

Two novel immortal pancreatic beta-cell lines expressing and secreting human islet amyloid polypeptide do not spontaneously develop islet amyloid. Diabetes 48(10): 1962-1970, 1999

Chronic overproduction of islet amyloid polypeptide/amylin in transgenic mice: Lysosomal localization of human islet amyloid polypeptide and lack of marked hyperglycaemia or hyperinsulinaemia. Diabetologia 36(12): 1258-1265, 1993

The ability of rodent islet amyloid polypeptide to inhibit amyloid formation by human islet amyloid polypeptide has important implications for the mechanism of amyloid formation and the design of inhibitors. Biochemistry 49(5): 872-881, 2010

Spontaneous diabetes mellitus in transgenic mice expressing human islet amyloid polypeptide. Proceedings of the National Academy of Sciences of the United States of America 93(14): 7283-7288, 1996

Islet amyloid and islet amyloid polypeptide in cynomolgus macaques (Macaca fascicularis): an animal model of human non-insulin-dependent diabetes mellitus. Veterinary Pathology 33(5): 479-485, 1996

Genetic background determines the extent of islet amyloid formation in human islet amyloid polypeptide transgenic mice. American Journal of Physiology. Endocrinology and Metabolism 289(4): E703-E709, 2005

Islet amyloid formation associated with hyperglycemia in transgenic mice with pancreatic beta cell expression of human islet amyloid polypeptide. Proceedings of the National Academy of Sciences of the United States of America 93(8): 3492-3496, 1996

Genetic background determines the extent of islet amyloid formation in human islet amyloid polypeptide transgenic mice (vol 289, pg 706, 2005). American Journal of Physiology Endocrinology and Metabolism 290(1): E205, 2006

The effect of apolipoprotein E deficiency on islet amyloid deposition in human islet amyloid polypeptide transgenic mice. Diabetologia 46(1): 71-79, 2003

Oophorectomy promotes islet amyloid formation in human islet amyloid polypeptide transgenic mice. Diabetes 50(Suppl. 1): S184-S185, 2001

IL-1 mediates amyloid-associated islet dysfunction and inflammation in human islet amyloid polypeptide transgenic mice. Diabetologia 58(3): 575-585, 2015

Rosiglitazone treatment does not decrease amyloid deposition in transplanted islets from transgenic mice expressing human islet amyloid polypeptide. Transplantation Proceedings 45(2): 574-579, 2013