[ Nutrition ]

The Role of Cyclic AMP in the Control of Carbohydrate Metabolism

Increased gluconeogenesis has been suggested to account for all of the increase in basal glucose production in patients with non-insulin-dependent diabetes mellitus (NIDDM). Production was measured using a primed-continuous [6,6-2H2]glucose infusion and gluconeogenesis from 2H enrichment at carbons 2 and 5 of blood glucose on 2H2O ingestion. Similar studies using a biguanide, phenformin, have been conducted to compare the mode of action of these two compounds. Diabetes during pregnancy is associated with an increased risk of maternal and neonatal morbidity [3]. The degree to which the liver extracts portal glucose is not entirely agreed upon although a preponderance of evidence points to about a 5% extraction rate, following meals, which is dependent on a stimulation of glucokinase. The most well-studied function of cyclin D1 is activation of cyclin-dependent kinase 4 (CDK4), promoting progression of the cell cycle. Both ALT isoforms in the liver were increased in diabetic Goto-Kakizaki rats and during fasting.

(2) Inhibition of hepatic fatty acid oxidation: beta-aminobetaine (emeriamine) is a water-soluble carnitine analog and inhibition of CPT-1 in isolated hepatocytes is 100 times more sensitive than that in isolated cardiocytes and it suppresses both gluconeogenesis and ketogenesis by 60-80%. The activity of rat liver fructose-1,6-bisphosphatase was inhibited by ZMP with an apparent Ki of 370 μM. In primary hepatocytes, SA treatment decreased glucose production and the expression of G6Pase, PEPCK, and hepatocyte nuclear factor 4 alpha (HNF-4α) mRNA. Liver glucose overproduction, particularly gluconeogenesis is a key element of hyperglycemia in prediabetes and type 2 diabetes (Monnier et al. Human diabetes mellitus is recognized as the result of a basic genetic defect, the nature of which is undefined. This means that the reaction can go forward (breaking down glucose in glycolysis) or backward (towards glucose synthesis in gluconeogenesis) depending on the relative concetrations of the product and reactant metabolites. Tiwari and Rao[16] have in their review indicated and advocated the use of whole plant extracts in preference to isolated and pure compounds from plants articulating several draw backs of pure compounds, prominent amongst which is increased toxicity.

Whether or not cyclic AMP plays a regulatory role in basement membrane synthesis is presently unknown. Glucagon produced a 2-fold increase in ketone bodies and it is suggested that these were mainly derived from protein. This could be secondary to basement membrane thickening, but there is also evidence that the cyclic AMP mechanism may be defective. At another level, the role of cyclic AMP is more obvious: insulin deficiency leaves unopposed the actions of hormones which stimulate the production of cyclic AMP, thereby contributing to the glucose plethora and ketosis so often seen in the later stages of the disease.

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