This study is the first report on the multiexponential T2 relaxation of the 13C-1 carbon of glycogen. In contrast to T1 relaxation, which does not display observable multiexponential decay behavior, T2 relaxation is described by a continuous distribution of T2 times. Changes in molecular weight and sample viscosity, which affect the overall mobility of the glycogen particle have little influence on T1 and T2 relaxation times. This is in contradiction with earlier results that T2 is dominated by the overall motion of the glycogen particles [L.-H. Zang Biochemistry 29, 6815-6820 (1990)]. T1 depends strongly on the external field Bo and is almost temperature independent in the range 23-37 degrees C whereas T2 is field independent and varies appreciably with temperature. The experimental T1 and T2 relaxation data are shown to be consistent with existing theoretical models for relaxation, suitably modified to include a distribution of correlation times for the internal motions. The presence of fast decaying components (short T2) in the FID implies broad line components in the frequency spectrum and the corresponding need to appropriately set the integration limits for the quantification of the glycogen peak.

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Postischemic dysfunction was associated with a rise in end-diastolic pressure. This rise was effectively blocked by HOE 694. The drug was most effective when hearts were treated before ischemia, although partial protection was observed when administration was started on reperfusion. The action of HOE 694 strengthens the idea that Na(+)-H+ exchange during both ischemia and reperfusion contributes to contractile dysfunction.

In search for a nonmetabolized, superior glucose analogue to study the mechanism of glucose-induced glycogen synthesis, we have tested 2-deoxy-2-fluoro-alpha-D-glucopyranosyl fluoride, which inhibits muscle phosphorylase beta 10-fold better than dose glucose (Street, I.P., Armstrong, C.R., and Withers, S.G. (1986) Biochemistry 25, 6021-6027). In a gel-filtered liver extract, 0.6 mM analogue and 10 mM glucose equally accelerated the inactivation of phosphorylase and shortened the latency before the activation of glycogen synthase. The analogue was not measurably defluorinated or phosphorylated by intact hepatocytes, as monitored by 19F NMR. When added to isolated hepatocytes, 10 mM analogue inactivated phosphorylase more extensively than did 50 mM glucose, but unlike glucose, it did not result in the activation of glycogen synthase. Therefore, the binding of glucose to phosphorylase alpha can account for the inactivation of phosphorylase, but the metabolism of glucose (probably to Glc-6-P) appears to be required to achieve activation of glycogen synthase. The livers of overnight-fasted, anesthetized mice contained appreciable amounts of both phosphorylase alpha and glycogen synthase alpha, without net glycogen accumulation. Likewise, hepatocytes isolated from fasted rats and incubated with 10 mM glucose contained 41% of phosphorylase and 32% of glycogen synthase in the alpha form, and these values remained stable for 1 h, while glycogen accumulated at only 22% of the rate expected from the glycogen synthase activity. The addition of 10 mM analogue decreased phosphorylase alpha to 10% without significant change in glycogen synthase alpha (38%), but with a 4-fold increased rate of glycogen accumulation. These findings imply that synthase alpha is fully active in the liver of the fasted animal and that the absence of net glycogen synthesis is due to continuous glycogenolysis by phosphorylase alpha.

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