Elevated glucose concentrations inhibit DNA synthesis and expression of c-myc in cultured hepatocytes.

Abstract:

:Glucose depressed DNA synthesis in rat hepatocytes in primary culture. As compared to controls cultured with 5.6 mM glucose, maximal (> or = 75%) inhibition was obtained at 20-30 mM, and half-maximal effect at 10-15 mM. Comparison of D- and L-glucose showed that the effect was specific for the D-form. Maximal inhibition required the presence of glucose during the first 24 hours of culture. The expression of the c-myc gene was reduced when the hepatocytes were cultured in the presence of elevated glucose. The responses to epidermal growth factor, insulin and vasopressin, in terms of percentual stimulation of DNA synthesis, were qualitatively similar at 5.6 and 16.8 mM glucose, while glucagon stimulated more strongly when the glucose concentration was increased; glucagon at concentrations > or = 1 nM reversed the inhibition by glucose. 8-Br-cAMP mimicked the effect of glucagon. These results suggest that an increase in the level of glucose depresses hepatocyte DNA synthesis. The effect is associated with lowered expression of the c-myc gene and is counteracted by cAMP.

authors

Dajani OF,Refsnes M,Guren TK,Horn RS,Thoresen GH,Christoffersen T

doi

10.1006/bbrc.1994.2097

subject

Has Abstract

pub_date

1994-08-15 00:00:00

pages

1476-82

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(84)72097-3

journal_volume

202

pub_type

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