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OBJECTIVE Human islet amyloid polypeptide (hIAPP), also named amylin, is a pancreatic beta cell protein implicated in the pathogenesis of pancreatic islet amyloid formation and type 2 diabetes mellitus. To study the (patho)physiological roles of hIAPP, we have generated transgenic mice that overexpress hIAPP mRNA, in relation to endogenous mouse IAPP (mIAPP) mRNA, in pancreatic beta cells. The biological activity of human and mouse IAPP derived from pancreatic extracts was determined. METHODS Pancreatic and plasma extracts of transgenic and control mice were analyzed by reversed-phase high-performance liquid chromatography (HPLC) and radioimmunoassay, yielding a separation of hIAPP from mIAPP. Biological activity of immunoreactive human and mouse IAPP components derived from pancreatic extracts was assessed by calcitonin receptor-mediated stimulation of cyclic AMP accumulation in T47D human breast carcinoma cells. RESULTS The predominant immunoreactive human and mouse IAPP gene products had the retention times on HPLC analysis of the corresponding synthetic peptides. The ratio of bioactive over immunoreactive hIAPP and mIAPP was 0.93 +/- 0.18 and 1.19 +/- 0.56 respectively. In extracts of two plasma pools from 4 transgenic animals, hIAPP was 4.6- to 7-fold more abundant than mIAPP. CONCLUSIONS This study has shown that correctly processed hIAPP produced in transgenic mouse pancreatic beta cells exhibits full biological activity. The results validate these transgenic mice for the study of (patho)physiological roles of hIAPP in vivo.
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C Oosterwijk, and
M A Blankenstein, and
C J Lips, and
J A Fischer, and
J W Höppener
April 1995,
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K L van Hulst, and
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M A Blankenstein, and
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J W Höppener
February 2001,
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K L van Hulst, and
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October 1994,
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K L van Hulst, and
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December 1993,
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June 1997,
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme,
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December 1998,
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January 1994,
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May 2003,
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January 2010,
Diabetes,
K L van Hulst, and
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July 1996,
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