Nuclear magnetic resonance studies of hepatic glucose metabolism in humans

Nuclear magnetic resonance (NMR) spectroscopy has made noninvasive and repe titive measurements of human hepatic glycogen concentrations possible. Moni toring of liver glycogen in real-time mode has demonstrated that glycogen c oncentrations decrease linearly and that net hepatic glycogenolysis contrib utes only about 50 percent to glucose production during the early period of a fast. Following a mixed meal, hepatic glycogen represents approximately 20 percent of the ingested carbohydrates, while only about 10 percent of an intravenous glucose load is retained by the liver as glycogen. During mixe d-meal ingestion, poorly controlled type 1 diabetic patients synthesize onl y about 30 percent of the glycogen stored in livers of nondiabetic humans s tudied under similar conditions. Reduced net glycogen synthesis can be impr oved but not normalized by short-term, intensified insulin treatment. A dec reased increment in liver glycogen content following meals was also found i n patients with maturity-onset diabetes of the young due to glucokinase mut ations (MODY2). In patients with poorly controlled type 2 diabetes, fasting hyperglycemia can be attributed mainly to increased rates of endogenous gl ucose production, which was found by C-13 NMR to be due to increased rates of gluconeogenesis. Metformin treatment improved fasting hyperglycemia in t hese patients through a reduction in hepatic glucose production, which coul d be attributed to a decrease in gluconeogenesis. In conclusion, NMR spectr oscopy has provided new insights into the pathogenesis of hyperglycemia in type 1, type 2, and MODY diabetes and offers the potential of providing new insights into the mechanism of action of novel antidabetic therapies.