Mechanism responsible for the hypoglycemic action of 2-alkoxy-2-propenylidene methanaminiums

Robert Harris, George A. Cook, Roger D. McDermott, Keith M. Robinson

Research output: Contribution to journalArticle

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Abstract

2-Alkoxy-2-propenylidene methanaminiums inhibited gluconeogenesis and stimulated glycolysis by hepatocytes isolated from 48-h-fasted rats and fasted-refed rats, respectively. The order of effectiveness of these compounds was the same as the hypoglycemic response of intact rats found in other studies, i.e., butoxy > propoxy > ethoxy derivative. Lactate/pyruvate and β-hydroxybutyrate/acetoacetate ratios were elevated whereas cellular ATP concentration was decreased by these compounds. The butoxy derivative inhibited the oxidation of [U-14C]glucose to 14CO2 but increased glucose utilization and lactate accumulation by isolated rat diaphragms. The butoxy derivative also inhibited site I reversed electron transfer and the oxidation of NAD+-linked substrates but not succinate by isolated rat liver mitochondria. Methanaminium-induced hypoglycemia in intact rats was accompanied by an increase in blood lactate concentration as well as blood β-hydroxybutyrate to acetoacetate ratio. The hypoglycemia caused by these compounds is proposed to be due to inhibition of glucose synthesis in the liver along with increased glucose utilization in peripheral tissues, both for want of ATP as a consequence of inhibition of site I electron transfer.

Original languageEnglish
Pages (from-to)522-530
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume238
Issue number2
DOIs
StatePublished - May 1 1985

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Hypoglycemic Agents
Rats
Hydroxybutyrates
Glucose
Lactic Acid
Derivatives
Hypoglycemia
Liver
Blood
Adenosine Triphosphate
Electrons
Oxidation
Mitochondria
Gluconeogenesis
Liver Mitochondrion
Succinic Acid
Glycolysis
Diaphragms
Diaphragm
Pyruvic Acid

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Mechanism responsible for the hypoglycemic action of 2-alkoxy-2-propenylidene methanaminiums. / Harris, Robert; Cook, George A.; McDermott, Roger D.; Robinson, Keith M.

In: Archives of Biochemistry and Biophysics, Vol. 238, No. 2, 01.05.1985, p. 522-530.

Research output: Contribution to journalArticle

Harris, Robert ; Cook, George A. ; McDermott, Roger D. ; Robinson, Keith M. / Mechanism responsible for the hypoglycemic action of 2-alkoxy-2-propenylidene methanaminiums. In: Archives of Biochemistry and Biophysics. 1985 ; Vol. 238, No. 2. pp. 522-530.
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