SODIUM FLUOROACETATE DIABETES: INSULIN AND CARBOHYDRATE TOLERANCE AND THE ANTIKETOGENIC EFFECTS OF GLUCOSE AND FRUCTOSE

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Abstract
THE locus of the metabolic defect in diabetes mellitus is still under debate, as is the site of action of insulin. The discovery that sodium fluoroacetate (SFA) precipitates a severe, but temporary, diabetes in the rat (1, 2, 3) offers an interesting opportunity in the study of the comparative biochemistry of diabetes since the basic metabolic disturbance due to SFA is reasonably well established. Fluoroacetate exerts its toxic effect only after its conversion by the tissues to fluorocitrate; the latter compound inhibits the enzyme aconitase in the Krebs cycle, resulting in an accumulation of citrate in the tissues (4). The temporary hyperglycemia and ketosis which ensues may be interpreted as the consequence of the Krebs cycle blockade with resulting loss of energy for phosphorylation of glucose, or its penetration into the cell, although the possibility of diminished insulin production by the beta cells as a consequence of the poisoning has not been ruled out (1, 2).