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Modulation of glucagon-induced glucose production by dexfenfluramine in rat hepatocytes


, : Modulation of glucagon-induced glucose production by dexfenfluramine in rat hepatocytes. Biochemical Journal 310: 61-66

The mechanism of the antihyperglycaemic action of dexfenfluramine (DEXF) was investigated in isolated rat hepatocytes exposed to glucagon. Preincubation of hepatocytes with DEXF caused a dose-dependent inhibition of cyclic AMP formation by 100 nM glucagon (Ki = 0.29 mM) that was almost complete at 1 mM DEXF. Surprisingly, glucagon-induced phosphorylase activation was not affected by DEXF despite the significant drop in cyclic AMP levels. Glucose production stimulated by glucagon was inhibited by up to 48% by 1 mM DEXF, and the rate of glucose production correlated positively with the steady-state concentration of glucose 6-phosphate. DEXF also partially restored lactate + pyruvate production which was abolished by an optimal concentration of glucagon. Although DEXF was not able to prevent the inactivation of pyruvate kinase by glucagon, the lack of further accumulation of phosphoenolpyruvate in DEXF-treated cells supports the conclusion that the flux through pyruvate kinase is stimulated, probably via the increase in fructose 2,6-bisphosphate, thereby increasing glycolysis. Our results thus indicate that DEXF counteracts the inhibition of glycolysis by glucagon and that this property might contribute to the antihyperglycaemic effect of this drug. Furthermore, this study shows that, in the presence of the drug, glucagon caused phosphorylase activation and pyruvate kinase inactivation without a significant increase in cyclic AMP levels.

US$19.90

PMID: 7646473

DOI: 10.1042/bj3100061


Other references

Molot, P.M.; Simone, J., 1967: A method of inoculating Maize seeds with Fusarium species. Maize seeds with a high germinating capacity are soaked for 4 hr in running water and drained. Cultures on oatmeal agar are kept at 22 degrees C under artificial light for 16 hr/day for c. 20 days. After removing excess medium they are stirred wit...

Gorniak, P.; Roy, D., 2007: Situated language understanding as filtering perceived affordances. We introduce a computational theory of situated language understanding in which the meaning of words and utterances depends on the physical environment and the goals and plans of communication partners. According to the theory, concepts that groun...

Lalrinzuali, K.; Vabeiryureilai, M.; Jagetia, G.Chandra., 2016: Investigation of the Anti-Inflammatory and Analgesic Activities of Ethanol Extract of Stem Bark of Sonapatha Oroxylum indicum In Vivo. Inflammation is all a pervasive phenomenon, which is elicited by the body in response to obnoxious stimuli as a protective measure. However, sustained inflammation leads to several diseases including cancer. Therefore it is necessary to neutralize...

Jones M.J., 1987: Soil water and crop production in botswana. This paper draws on the results of a five-year project on the agronomy, crop physiology and soil physics of the cropping of sorghum and subsidiary crops at several sites in Botswana. The low and erratic yields usually obtained stem largely from th...

Wernert, Michel, 1993: Paul Wernert. Bulletin de la Societe d'Histoire Naturelle de Colmar1991-1992(1993); 61: 25-27

Springer, S.; Lindner, T.; Steinbach, G.; Selbitz, H.J., 2001: Investigation of the efficacy of a genetically-stabile live Salmonella typhimurium vaccine for use in swine. Hybrid swine (Landrace x Pietrain) aged 3-4 weeks were immunized twice at an interval of 3 weeks solely by the oral route and by the oral/parenteral route to evaluate the efficacy of a live S. typhimurium vaccine. In each experiment a control grou...

Miura, Y., 1989: Hemopoietic stem cells. Nihon Naika Gakkai Zasshi. Journal of the Japanese Society of Internal Medicine 78(12): 1721-1725

Neto, PS., 1982: Aspectos bionomicos e desenvolvimento de Theristicus caudatus Boddaert, 1783 Aves, Threskiornithidae. Dusenia, 134: 145-149

Lachiewicz, A.M.; Williams, F.N.; Carson, S.S.; Trexler, J.M.; Nielsen, C.A.; van Duin, D.; Weber, D.J.; Williams, S.D.; Jones, S.W.; Cairns, B.A., 2017: Improving Research Enrollment of Severe Burn Patients. Enrolling severely burn injured patients into prospective research studies poses specific challenges to investigators. The authors describe their experience of recruiting adults with ≥20% TBSA burns or inhalation injury admitted to a single acad...

Anonymous, 1960: Student Loyalty Oaths: Chances Nil for Outright Repeal; Compromise Possible. Science 131(3411): 1425-1427