R. Gasa et al., GLUCOSE REGULATION OF ISLET AMYLOID POLYPEPTIDE GENE-EXPRESSION IN RAT PANCREATIC-ISLETS, American journal of physiology: endocrinology and metabolism, 35(4), 1997, pp. 543-549
Intracellular pathways by which glucose regulates islet amyloid polype
ptide (IAPP) gene expression in pancreatic islets were studied. IAPP m
RNA levels were threefold higher in islets cultured with 16.7 mM gluco
se compared with control (5.5 mM glucose). Mannose and amino acids but
not 2-deoxyglucose or 6-deoxyglucose mimicked the effect of glucose.
Mannoheptulose (a glycolysis inhibitor) and verapamil and diazoxide (w
hich affect calcium signaling pathway) abolished the difference in isl
et IAPP mRNA content between high and low glucose. At low glucose, IAP
P mRNA levels were increased 1.9-fold in islets treated with forskolin
or dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) but not wi
th 12-O-tetradecanoylphorbol 13-acetate. Insulin mRNA levels were 1.6-
fold higher in islets cultured at high glucose than controls; glucose
metabolism was required, whereas no effects of cAMP or diazoxide were
observed. IAPP and insulin were cosecreted into the media. We conclude
that glucose regulation of LAPP mRNA abundance requires intracellular
metabolism of the hexose and that calcium may serve as a mediator of
this effect; cAMP but not protein kinase C possibly participates in th
is regulation.