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Expression of wild-type and mutant S20G hIAPP in physiologic knock-in mouse models fails to induce islet amyloid formation, but induces mild glucose intolerance
- Source :
- Journal of Diabetes Investigation. 3:138-147
- Publication Year :
- 2011
- Publisher :
- Wiley, 2011.
-
Abstract
- Aims/Introduction: Human islet polypeptide S20G mutation (hIAPPS20G) is associated with earlier onset type 2 diabetes and increased amyloidogenicity and cytotoxicity in vitro vs wild-type hIAPP (hIAPPWT), suggesting that amyloidogenesis may be pathogenic for type 2 diabetes. We compared the contributions of hIAPPS20G and hIAPPWT toward intra islet amyloid formation and development of type 2 diabetes in a unique physiologic knock-in mouse model. Materials and Methods: We replaced the mouse IAPP gene (M allele) with hIAPPWT (W allele) and hIAPPS20G (G allele) via homologous recombination and backbred transgenic mice against C57Bl/6 strain 5 generations to minimize genetic variation. Mice (3 month old) were maintained on control (CD) or high fat diet (HFD) for 15 months and studied at 3 month intervals by oral glucose tolerance testing (OGTT) and pancreas histology to assess glucose homeostastis, amyloidogeneisis, islet mass, β cell replication, and apoptosis. Results: IAPP blood levels were indistinguishable in all mice. WW and GW mice maintained on both diets lacked intraislet amyloid at all ages. On both diets relative to MM controls WW and GW mice exhibit glucose intolerance (P
- Subjects :
- Genetically modified mouse
medicine.medical_specialty
Amyloid
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
030209 endocrinology & metabolism
Type 2 diabetes
Biology
03 medical and health sciences
0302 clinical medicine
Internal medicine
Diabetes mellitus
Internal Medicine
medicine
Secretion
030304 developmental biology
2. Zero hunger
0303 health sciences
geography
geography.geographical_feature_category
Insulin
Wild type
General Medicine
medicine.disease
Islet
Endocrinology
Subjects
Details
- ISSN :
- 20401116 and 20401124
- Volume :
- 3
- Database :
- OpenAIRE
- Journal :
- Journal of Diabetes Investigation
- Accession number :
- edsair.doi...........0daecb6efdaf66d500547e276b0807cc