Contribution of gluconeogenesis to overall glucose output in diabetic and nondiabetic men.
Increased hepatic glucose output is the main cause of fasting hyperglycemia in non-insulin dependent diabetes mellitus. Due to difficulties in obtaining a quantitative estimate of gluconeogenesis in vivo, the relative contribution of gluconeogenesis and glycogenolysis to this increased hepatic glucose output was unknown. The application in vivo of a new isotopic approach based on a mathematical model of the Krebs cycle enabled us to obtain a quantitative estimate of gluconeogenesis in vivo. Using this approach, gluconeogenesis was found to account for approximately 28% and approximately 97% of overall hepatic glucose output in healthy volunteers in the postabsorptive and in the fasted state respectively. When this technique was used to compare gluconeogenesis rates in non-insulin dependent diabetes mellitus and nondiabetic patients, gluconeogenesis was found to be increased threefold in the patients with non-insulin dependent diabetes mellitus (12.7 +/- 1.6 mu vs 3.6 +/- 0.6 mumol/Kg/min) and to be significantly correlated with fasting plasma glucose. Furthermore, the increase in gluconeogenesis could explain more than 80% of the increase in overall hepatic glucose output in patients with non-insulin dependent diabetes mellitus. In conclusion, in non-insulin dependent diabetes mellitus, gluconeogenesis, as measured by a new isotopic technique, is increased and this increase represents the main cause for increased overall hepatic glucose output and fasting hyperglycemia.
Consoli
A
A
Clinical Research Center, University of Pittsburgh, Presbyterian-University Hospital, PA 15261.
Nurjhan
N
N
D002250:Carbon Radioisotopes; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male
D002250:Carbon Radioisotopes; D006003:Glycogen; D005947:Glucose