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Effect of tolbutamide on sup 14 C-sodium bicarbonate and sup 14 C-alanine metabolism in isolated rat hepatocytes

Conference · · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)
OSTI ID:6057159
; ; ; ;  [1]
  1. Northeast Louisiana Univ., Monroe (United States)

Tolbutamide (TOLB) is a sulfonylurea commonly used in the treatment of noninsulin-dependent diabetes mellitus. Studies have shown that TOLB affects gluconeogenesis and glycolysis from various substrates in the liver. Specifically, TOLB inhibits gluconeogenesis from lactate in a dose-dependent manner. In order to further clarify tolbutamide's mechanism of action, its effect on the incorporation of {sup 14}C from NaH{sup 14}CO{sub 3} and {sup 14}C-alanine into glucose, lactate or pyruvate in the presence of lactate was measured. Rat hepatocytes were incubated with lactate (2.0 mM) with or without TOLB (1.0 mM) in the presence of NaH{sup 14}CO{sub 3} or {sup 14}C-alanine. TOLB inhibited the incorporation of C{sup 14} from NaHCO{sub 3} and alanine into glucose by 55 and 56%, respectively. TOLB did not alter the incorporation of C{sup 14} from NaHCO{sub 3} into lactate or pyruvate. TOLB did not affect the incorporation of {sup 14}C from alanine into lactate but produced a pooling of {sup 14}C as pyruvate. The authors data support studies demonstrating the TOLB produces its actions, in part, by increasing the concentration of fructose-2,6-bisphosphate and inhibiting pyruvate carboxylase.

OSTI ID:
6057159
Report Number(s):
CONF-9104107--
Journal Information:
FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (United States) Vol. 4:3; ISSN 0892-6638; ISSN FAJOE
Country of Publication:
United States
Language:
English