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 glucoregulatory role of islet amyloid polypeptide (IAPP), we have created transgenic mice 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 abnormalities 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.
Department of Chemistry and Biotechnology Research, Lilly Research Labs, Lilly Corporate Center, Indianapolis, IN 46285.
N
N
Fox
J
J
Schrementi
M
M
Nishi
S
S
Ohagi
S J
SJ
Chan
J A
JA
Heisserman
G T
GT
Westermark
A
A
Leckström
P
P
Westermark
D F
DF
Steiner
D000682:Amyloid / Q000097:blood / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D003924:Diabetes Mellitus, Type 2; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats
D000682:Amyloid; D058228:Islet Amyloid Polypeptide