Abstract
Islet amyloid polypeptide forms islet amyloid deposits in non-insulin-dependent diabetes
mellitus. We have generated transgenic mice which express human islet amyloid polypeptide
in their pancreatic beta cells yet do not develop islet amyloid deposits despite producing
levels of the amyloidogenic human peptide 2-3 fold higher than the native (mouse)
peptide. To determine whether marked overproduction of islet amyloid polypeptide is
a potential cause of islet amyloid formation, we increased expression of this transgene
by producing homozygous transgenic animals and by making heterozygous mice experimentally
insulin resistant with nicotinic acid. Pancreatic content of islet amyloid polypeptide-like
immunoreactivity in homozygous and nicotinic acid-treated mice was 2-fold (25 ± 7
fmol/µg; n = 6) and 3.5-fold (47 ± 20 fmol/µg; n = 3) higher, respectively, than that
of untreated heterozygous animals (13 ± 2 fmol/µg; n = 11; both p < 0.05). Despite
this marked increase in production of islet amyloid polypeptide, neither group of
mice developed gross islet amyloid deposits even after 16 months of age. We conclude
that overproduction of islet amyloid polypeptide, even as produced by extreme insulin
resistance, is not in itself sufficient for islet amyloid formation.
Key words
Transgenic Mice - Non-Insulin-Dependent Diabetes Mellitus - Insulin - Pancreatic Beta
Cell - Hyperglycemia - Nicotinic Acid
