+ 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

Postnatally disturbed pancreatic islet cell distribution in human islet amyloid polypeptide transgenic mice



Postnatally disturbed pancreatic islet cell distribution in human islet amyloid polypeptide transgenic mice



Regulatory Peptides 113(1-3): 89-94



Objective: Islet amyloid polypeptide (IAPP)/amylin is produced by the pancreatic islet beta-cells, which also produce insulin. To study potential functions of IAPP, we have generated transgenic mice overexpressing human IAPP (hIAPP) in the beta-cells. These mice show a diabetic phenotype when challenged with an oral glucose load. In this study, we examined the islet cytoarchitecture in the hIAPP mice by examining islet cell distribution in the neonatal period, as well as 1, 3 and 6 months after birth. Results: Neonatal transgenic mice exhibited normal islet cell distribution with beta-cells constituting the central islet portion, whereas glucagon and somatostatin-producing cells constituted the peripheral zone. In contrast, in hIAPP transgenic mice at the age of 1 month, the glucagon-immunoreactive (IR) cells were dispersed throughout the islets. Furthermore, at the age of 3 and 6 months, the islet organisation was similarly severely disturbed as at 1 month. Expression of both endogenous mouse IAPP and transgenic hLAPP was clearly higher in 6-month-old mice as compared to newborns, as revealed by mRNA in situ hybridisation. Conclusions: Mice transgenic for hIAPP have islets with disrupted islet cytoarchitecture in the postnatal period, particularly affecting the distribution of glucagon-IR cells. This islet cellular phenotype of hIAPP transgenic mice is similar to that of other mouse models of experimental diabetes and might contribute to the impaired glucose homeostasis.

Please choose payment method:






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

Accession: 011174583

Download citation: RISBibTeXText

PMID: 12686466

DOI: 10.1016/s0167-0115(02)00298-7


Related references

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

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

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

Treatment With Growth Hormone and Dexamethasone in Mice Transgenic for Human Islet Amyloid Polypeptide Causes Islet Amyloidosis and -Cell Dysfunction. Diabetes 45(8): 1094-1101, 1996

Treatment with growth hormone and dexamethasone in mice transgenic for human islet amyloid polypeptide causes islet amyloidosis and beta-cell dysfunction. Diabetes 45(8): 1094-1101, 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

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

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

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

Exendin-4 increases islet amyloid deposition but offsets the resultant beta cell toxicity in human islet amyloid polypeptide transgenic mouse islets. Diabetologia 54(7): 1756-1765, 2011

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

cJUN N-terminal kinase (JNK) activation mediates islet amyloid-induced beta cell apoptosis in cultured human islet amyloid polypeptide transgenic mouse islets. Diabetologia 55(1): 166-174, 2012

Intra- and extracellular amyloid fibrils are formed in cultured pancreatic islets of transgenic mice expressing human islet amyloid polypeptide. Proceedings of the National Academy of Sciences of the United States of America 91(18): 8467-8471, 1994