HUMAN ISLET AMYLOID POLYPEPTIDE TRANSGENIC MICE AS A MODEL OF NON-INSULIN-DEPENDENT DIABETES-MELLITUS (NIDDM)

To model islet amyloidogenesis in NIDDM and explore the glucoregulator y role of islet amyloid polypeptide (IAPP), we have created transgenic mice containing a rat insulin-I promoter-human IAPP fusion gene. Expr ession of human IAPP was localized to the islets of Langerhans, anteri or pituitary and brain in transgenic animals; blood IAPP levels were e levated 5-fold while fasting glucose levels remained normal. Amyloid d eposits have not been detected in transgenic islets suggesting that ot her co-existing abnormalitites in NIDDM may be required for the format ion of islet amyloid. These animals provide a unique model for explori ng this hypothesis and other proposed functions of IAPP.