Islet Amyloid Polypeptide (IAPP) Transgenic Rodents as Models for Type 2 Diabetes
Autor: | Aleksey V. Matveyenko, Peter C. Butler |
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Rok vydání: | 2006 |
Předmět: |
Amyloid
endocrine system medicine.medical_specialty endocrine system diseases Transgene medicine.medical_treatment Mice Transgenic Type 2 diabetes Biology General Biochemistry Genetics and Molecular Biology Mice Insulin resistance Insulin-Secreting Cells Internal medicine medicine Animals Humans geography geography.geographical_feature_category Insulin Type 2 Diabetes Mellitus General Medicine Islet medicine.disease Islet Amyloid Polypeptide Rats Disease Models Animal Endocrinology Diabetes Mellitus Type 2 Animal Science and Zoology Beta cell |
Zdroj: | ILAR Journal. 47:225-233 |
ISSN: | 1084-2020 |
Popis: | Blood glucose concentrations are maintained by insulin secreted from beta-cells located in the islets of Langerhans. There are approximately 2000 beta-cells per islet, and approximately one million islets of Langerhans scattered throughout the pancreas. The islet in type 2 diabetes mellitus (T2D) has deficient beta-cell mass due to increased beta-cell apoptosis and islet amyloid derived from islet amyloid polypeptide (IAPP). Accumulating evidence implicates toxic IAPP oligomers in the mediation of beta-cell apoptosis in T2D. Humans, monkeys, and cats express an amyloidogenic toxic form of IAPP and spontaneously develop diabetes characterized by islet amyloid deposits. However, longitudinal studies of islet pathology in humans are impossible, and studies in nonhuman primates and cats are costly and impractical. Rodent IAPP is not amyloidogenic, thus commonly used rodent models of diabetes do not recapitulate islet pathology in humans. To investigate the diabetogenic role of human IAPP (h-IAPP), several mouse models and, more recently, a rat model transgenic for h-IAPP have been developed. Studies in these models have revealed that the toxic effect of h-IAPP on beta-cell apoptosis demonstrates a threshold-dependent effect. Specifically, increasing h-IAPP transgene expression by breeding or induction of insulin resistance leads to increased beta-cell apoptosis and diabetes. These transgenic rodent models for h-IAPP provide an opportunity to elucidate the mechanisms responsible for h-IAPP-induced beta-cell apoptosis further and to test novel approaches to the prevention and treatment of T2D. |
Databáze: | OpenAIRE |
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