Islet amyloid polypeptide and insulin gene expression are regulated
in parallel by glucose in vivo in rats.
Mulder, Hindrik, Bo Ahr[acute]en, and Frank Sundler.
Department of Physiology and Neuroscience, Section for
Neuroendocrine Cell Biology, University of Lund, S-223 62 Lund,
Sweden
APStracts 3:0152E, 1996.
Islet amyloid polypeptide (IAPP) is a novel amyloid-forming _-cell
hormone with putative roles in glucose metabolism and NIDDM
pathogenesis. To study how IAPP and insulin expression are regulated
by glucose, rats were fasted for 48 hours followed by administration
of glucose at repeated four-hour intervals; IAPP and insulin mRNA
levels were determined by quantitative in situ hybridization. Fasting
markedly reduced IAPP and insulin mRNA levels. Two (6 h) and four (14
h) glucose injections dose-dependently increased the levels of both
mRNAs; the effects were matched by similar changes in plasma glucose
levels. Actinomycin D blocked the glucose-induced increase in IAPP
expression. IAPP and insulin mRNA levels were significantly
correlated over the range of glucose levels. The parallel regulation
of IAPP and insulin gene expression by glucose is consistent with a
role for IAPP in glucose homeostasis. Thus, under hyperglycemic
conditions, such as NIDDM, IAPP gene expression is likely to
increase. Hence, IAPP could by elevated local concentrations
contribute to amyloid formation, and/or affect metabolism
unfavourably by inhibition of insulin release and action.
Received 7 May 1996; accepted in final form 25 July 1996.
APS Manuscript Number E224-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 August 1996