geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

A proposal for the locus of metformin's clinical action: potentiation of the activation of pyruvate kinase by fructose-1,6-diphosphate


, : A proposal for the locus of metformin's clinical action: potentiation of the activation of pyruvate kinase by fructose-1,6-diphosphate. Medical Hypotheses 52(2): 89-93

Reduction of hepatic glucose output has been shown to be the chief basis for metformin's clinical benefit in diabetes, and the balance of the evidence suggests that this reflects inhibition of gluconeogenesis. Recent research with hepatocyte cell cultures demonstrates increased flux through pyruvate kinase in metformin-treated cells. An analysis of the conditions under which clinically relevant concentrations of metformin inhibit gluconeogenesis in hepatocyte cultures prompts the hypothesis that metformin potentiates the allosteric activation of pyruvate kinase by fructose-1,6-diphosphate. This model rationalizes several salient features of metformin's clinical activity: its ability to reduce hepatic triglyceride synthesis, its appetite-suppressant effect, and its failure to induce hypoglycemia.

US$19.90

PMID: 10340287

DOI: 10.1054/mehy.1997.0597


Other references

Božić, B.; Korać, J.; Stanković, D.M.; Stanić, M.; Popović-Bijelić, A.; Bogdanović Pristov, J.; Spasojević, I.; Bajčetić, M., 2017: Mechanisms of redox interactions of bilirubin with copper and the effects of penicillamine. Toxic effects of unconjugated bilirubin (BR) in neonatal hyperbilirubinemia have been related to redox and/or coordinate interactions with Cu<sup>2+</sup>. However, the development and mechanisms of such interactions at physiological p...

Kikkenborg Berg, S.; Pedersen, P.U., 2008: Perception of general health in adults with congenital heart disease who no longer attend medical follow-up. Numerous patients with congenital heart disease (CHD) do not attend regular follow-up. How these patients perceive their health is unknown. A news story recently reached the front pages in Denmark, stating that patients with CHD not attending medi...

Takeuchi, T.; Miyasaka, N.; Kawai, S.; Sugiyama, N.; Yuasa, H.; Yamashita, N.; Sugiyama, N.; Wagerle, L.Craig.; Vlahos, B.; Wajdula, J., 2015: Pharmacokinetics, efficacy and safety profiles of etanercept monotherapy in Japanese patients with rheumatoid arthritis: review of seven clinical trials. Abstract Conventional synthetic disease-modifying anti-rheumatic drugs, including methotrexate, may not be tolerated by all patients with rheumatoid arthritis (RA), and limited international data for etanercept (ETN) monotherapy are available. The...

Van Steenis, C.G.G.J., 1957: Lamiodendron, a new genus of Papuan Bignoniaceae. Description of LAMIODENDRON magnificum from d'Entrecasteaux and Louisiade Island; allied to some southeastern Asian genera.

Johannsson, O.E.; Bergman, H.L.; Wood, C.M.; Laurent, P.; Kavembe, D.G.; Bianchini, A.; Maina, J.N.; Chevalier, C.; Bianchini, L.F.; Papah, M.B.; Ojoo, R.O., 2014: Air breathing in Magadi tilapia Alcolapia grahami, under normoxic and hyperoxic conditions, and the association with sunlight and reactive oxygen species. Observations of the Magadi tilapia Alcolapia grahami in hot, highly alkaline Lake Magadi revealed that they air breathe not only during hypoxia, as described previously, but also during normoxia and hyperoxia. Air breathing under these latter cond...

Horakova, Z.; Hach, V.; Roth, Z.; Matouskova, S.Olkova, H., 1956: Local anesthetic action and further pharmacological properties of alkoxyl derivatives of xylocaine analogues. Physiologia Bohemoslovenica 5(4): 448-459

Virtanen, M.; Ranki, M., 1983: Nucleic acid hybridization--a new method of diagnosing microbial infections. Duodecim; Laaketieteellinen Aikakauskirja 99(19): 1416-1422

Garoyan, L.; Thor, E., 1983: Economic trends of major sectors of the California canning industry, November 1981. The report comprises eight sections, plus supplemental material in the index, comprising: (1) statistics showing changes in consumption trends for food, some factors contributing to these changes and specific consumption trend changes for fruits a...

Cahal, M.F.; Cady, E.L., 1967: Secure appropriate consent. Gp 35(5): 181-183

Woodhead, D.S., 1977: The effects of chronic irradiation on the breeding performance of the guppy, Poecilia reticulata (Osteichthyes:Teleostei). The effects of chronic irradiation on the life-time breeding performance of the small tropical fish, Poecilia reticulata, have been investigated at mean dose-rates of 0.17, 0.40 and 1.27 rad hour-1. The total fecundity was markedly (P less than 0....