C-13-NUCLEAR MAGNETIC-RESONANCE SPECTROSCOPY STUDIES OF HEPATIC GLUCOSE-METABOLISM IN NORMAL SUBJECTS AND SUBJECTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS

To determine the effect of insulin-dependent diabetes mellitus (IDDM) on rates and pathways of hepatic glycogen synthesis, as well as flux t hrough hepatic pyruvate dehydrogenase, we used C-13-nuclear magnetic r esonance spectroscopy to monitor the peak intensity of the C1 resonanc e of the glucosyl units of hepatic glycogen, in combination with aceta minophen to sample the hepatic UDP-glucose pool and phenylacetate to s ample the hepatic glutamine pool, during a hyperglycemic-hyperinsuline mic clamp using [1-C-13]glucose. Five subjects with poorly controlled IDDM and six age-weight-matched control subjects were clamped at a mea n plasma glucose concentration of similar to 9 mM and mean plasma insu lin concentrations similar to 400 pM for 5 h. Rates of hepatic glycoge n synthesis were similar in both groups (similar to 0.43+/-0.09 mu mol /ml liver.min). However, flux through the indirect pathway of glycogen synthesis (3 carbon units -->--> glycogen) was increased by similar t o 50% (P < 0.05), whereas the relative contribution of pyruvate oxidat ion to TCA cycle flux was decreased by similar to 30% (P < 0.05) in th e IDDM subjects compared to the control subjects. These studies demons trate that patients with poorly controlled insulin-dependent diabetes mellitus have augmented hepatic gluconeogenesis and relative decreased rates of hepatic pyruvate oxidation. These abnormalities are not imme diately reversed by normalizing intraportal concentrations of glucose, insulin, and glucagon and may contribute to postprandial hyperglycemi a.