Human islet amyloid polypeptide transgenic mice as a model of non‐insulin‐dependent diabetes mellitus (NIDDM)

N Fox, J Schrementi, M Nishi, S Ohagi, SJ Chan… - FEBS …, 1993 - Wiley Online Library
N Fox, J Schrementi, M Nishi, S Ohagi, SJ Chan, JA Heisserman, GT Westermark
FEBS letters, 1993Wiley Online Library
To model islet amyloidogenesis in NIDDM and explore the glucoregulatory role of islet
amyloid polypeptide (IAPP), we have created transgenic micye containing a rat insulin‐I
promoter‐human IAPP fusion gene. Expression of human IAPP was localized to the islets of
Langerhans, anterior pituitary and brain in transgenic animals; blood IAPP levels were
elevated 5‐fold while fasting glucose levels remained normal. Amyloid deposits have not
been detected in transgenic islets suggesting that other co‐existing abnormalitites in NIDDM …
To model islet amyloidogenesis in NIDDM and explore the glucoregulatory role of islet amyloid polypeptide (IAPP), we have created transgenic micye containing a rat insulin‐I promoter‐human IAPP fusion gene. Expression of human IAPP was localized to the islets of Langerhans, anterior pituitary and brain in transgenic animals; blood IAPP levels were elevated 5‐fold while fasting glucose levels remained normal. Amyloid deposits have not been detected in transgenic islets suggesting that other co‐existing abnormalitites in NIDDM may be required for the formation of islet amyloid. These animals provide a unique model for exploring this hypothesis and other proposed functions of IAPP.
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