© Georg Thieme Verlag KG Stuttgart · New York
Citrate and Related Intermediates in Liver during Experimental Diabetes, Contrasted with Starvation
07 January 2009 (online)
1. The concentration of citrate and related intermediates in the livers of starved and diabetic rats has been measured by gas liquid chromatography; and, after in vivo labelling with pyruvate-1-14C, both their mean concentration and their specific activity have been determined.
2. After 48 hrs starvation, the mean concentration of malate was increased (132%) while there was a reduction in that of citrate (71%), α-keto-glutarate (α-KG) (37%) and succinate (66%); that of fumarate was unchanged. On in vivo labelling with pyruvate-1-14C we found that starvation increased malate labelling from pyruvate-1-14C but, relative to this, the specific activities of citrate and α-KG were lower than normal.
3. In contrast, in rats made diabetic by injection of alloxan or streptozotocin, while again malate was increased (128-160%), citrate was also increased (124-183%), and a positive correlation was found between these concentrations and the severity of the diabetes. In further contrast to starved rat liver, the hepatic contents of αKG, succinate and fumarate were normal or slightly increased. Diabetes due to streptozotocin or anti-insulin serum also caused an increase in malate labelling from pyruvate-1-14C similar to that in starvation, but relative to malate the specific activities of citrate and αKG were normal. In alloxan diabetes, this relative specific activity of these two intermediates in relation to malate was paradoxically greater than normal, possibly due to hepatotoxicity of the agent.
4. These findings suggest that hepatic citrate metabolism in starvation differs from that in experimental diabetes. They are consistent with the suggestion that the rate of citrate synthesis is diminished in starvation ketosis but do not support this view in experimental diabetes.
Experimental Diabetes - Starvation - Liver - Citrate - Malate - α-Ketoglutarate - Succinate - Pyruvate - Streptozotocin