Determination of endogenous gluconeogenesis and hepatic glycogenolysis in healthy and type 2 diabetic man by the combined use of non-invasive techniques

Research project P 13722 Determination of endogenous gluconeogenesis and glycogenolysis Michael RODEN 11.10.1999 Hyperglycernia of type 2 diabetes mellitus results from inadequate elevation of endogenous glucose production that can be attributed to an increase in endogenous; gluconeogenesis and/or hepatic glycogenolysis. In humans, measurement of endogenous gluconeogenesis is limited by several methodological and technical problems. A recently introduced method now allows to quantify the contribution of gluconeogenesis to glucose production from C5/C2 deuterium (2H) enrichments in blood glucose using gas chromatography-mass spectrometry following ingestion of deuterated water (2H2O). However, the required preparation of blood glucose is expensive, time- consuming, and does not provide information as to the enrichments in other carbons of glucose, which could have a major impact on the final results. In cooperation with the Institute of Pharmaceutic Chemistry, University of Graz, Austria, we currently develop a new technique using in vitro 2H NMR spectroscopy, which enables rapid determination of 2H-enrichments in all individual carbons (C1-C6), of blood glucose and thereby to directly quantify gluconeogenesis in man. To evaluate this method, rates of endogenous glucose production and glycogenolysis will be also determined from infusion rates of D-[6,6-2H]glucose and noninvasive measurements of hepatic glycogen using in vivo 13C NMR spectroscopy during prolonged fasting in healthy and type 2 diabetic subjects. This will provide information (i) on the time course of the percent and absolute contributions of endogenous gluconeogenesis and glycogenolysis to glucose production during physiological conditions of fasting in healthy subjects and (ii) on the respective roles of gluconeogenesis and glycogenolysis for the elevation of glucose production in type 2 diabetes mellitus.