Glucagon Plays an Important Role in the Excessive Production of Ketone Bodies in Diabetes Mellitus
If untreated, diabetes mellitus in animals, especially dogs, leads to high concentrations of ketone bodies in the blood. Diabetes mellitus occurs because of a lack of insulin, but the hepatic production of ketone bodies results from the unrestrained action of glucagon.
Even though serum concentrations of glucose are high in diabetes mellitus, the inability of the pancreas to secrete insulin leads to a Iowr insulin/ glucagon ratio; thus the liver is functioning solely under the direction of glucagon. Glucagon inhibits fatty-acid production from glucose, so malonyl CoA concentrations are low and CPT-I activity is high. Because of the lack of insulin to suppress adipose HSL, blood NEFA concentrations are high. The combination of high NEFA availability and unrestrained CPT-I activity results in rapid transport of fatty acids into the mitochondria with extensive ketone body production, even though blood glucose concentrations are high.
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