Noninvaive observation of hepatic glycogen formation in man by¹³C MRS after Orl and intravenous glucose administration

Abstract

The formation of glycogen in the liver of normal volunteers was followed noninvasively with 13C magnetic resonance spectroscopy (MRS) under two different conditions: a) intravenous infusion of [1-13C]glucose under hyperglycemic and hyperinsulinemic clamp conditions, and b) oral intake of glucose in the form of a bolus. For the intravenous infusion, [1-13C]glucose with an enrichment level of 99% was employed. The C1 signals of alpha- and beta-glucose could be detected in the human liver already after an infusion period of 8 min. However, an increase in the glycogen signal was observed only after a prolonged infusion of about 60 min. Changes in the glycogen signal correlated well with the time course of insulin and glucagon during the measurement. Experiments showed also that liver glycogen formation in man can be followed noninvasively by 13C-MRS using nonlabeled glucose or [1-13C]glucose with a low level of enrichment (6.6%). The use of nonlabeled glucose may therefore simplify the quantitation of net liver glycogen synthesis since it can be based directly on changes in the natural abundance 13C MRS glycogen signal, avoiding label dilution through the various metabolic pathways of glucose. The glucose uptake, estimated from the increase in the glycogen signal, was consistent with findings from more complex and invasive studies of glucose uptake in the liver. The average liver glycogen concentration in 12 h overnight fasted volunteers (n = 18) without any special dietary preparation was assessed to be 229 +/- 34 mM (minimum = 160 mM; maximum = 274 mM).

Alternative 1‐13C glucose infusion protocols for clinical 13C MRS examinations of the brain

“…Hyperglycemia was more pronounced in protocol A than in protocol B. In protocol C, the well-established profile of blood glucose after an oral glucose tolerance test (GTT) suggests the blood glucose achieved was Ͻ6.5 mM after 30 min (18). Blood glucose decreased more rapidly from its initial peak value in protocol A compared with protocol B (Fig.…”

“…administration and blood sampling were declined. The use of oral 1-13 C glucose has been previously reported for brain examinations by Watanabe et al (17) and for liver studies by Beckmann et al (18).…”

“…Few previous 13 C MRS studies have used oral administration of 1-13 C glucose to study metabolism in human subjects. We have found one brain study (17), which did not include a kinetic follow-up, and another of hepatic and muscle glycogen metabolism (18). Compared with our i.v.…”

“…A 13 C MRS study from Beckmann et al (18) demonstrated that about 10% of the administered glucose is retained in the liver during i.v. infusion, while about 29% is retained following oral ingestion.…”

Disordered Lipid Metabolism and the Pathogenesis of Insulin Resistance

“…The ratio of glycogen breakdown to glycogen synthesis provides relative rates of glycogen turnover (83,88,89,105). 13 C spectroscopy has recently also been used to trace the incorporation of infused 2-13 C-labeled acetate into glutamate in skeletal muscle and brain during a constant [2][3][4][5][6][7][8][9][10][11][12][13] C]acetate infusion. The rate of incorporation reflects tricarboxylic acid (TCA) cycle activity providing an index of mitochondrial function in muscle (or brain) (79).…”