Hormones like insulin and glucagon are known to affect the enzymes involved in glycogen metabolism. The [1-13C]-labeled glucose-[1-12C]glucose chase technique was used to assess flux rates through glycogen phosphorylase in healthy humans, showing that rate of hepatic glycogen synthesis depends on portal vein insulin, requiring portal vein insulin concentration in the range of 130-170 pmol.l-1 for half-maximal stimulation of glycogen synthesis (Roden et al. 1996a) (Figure 11.13), which is good agreement with that for suppression of glucose production by insulin (Rizza et al.1981). Further study (Petersen et al. 1998b) trying to sort out the effects of hyperglycaemia and hyperinsulinaemia per se on hepatic glycogen metabolism showed that promotion of hepatic glycogen cycling may be the mechanism by which insulin decreases glycogenolysis and glucose production during euglycaemia. Additional stimulation of hepatic glycogen synthesis by low dose fructose infusion (~3.5 ^mol.kg_1.min_1) during maximal insulin stimulation in healthy volunteers was measured by Petersen et al. (2001) in another pulse chase study, providing another possible therapeutic concept in both types of diabetes. The role of glucagon on hepatic glycogen cycling was studied using the [1-13C]glucose-[1-12C]glucose chase technique by Roden et al. (1996a) (Figure 11.13), showing that small changes in portal vein concentrations of insulin and glucagon independently affect hepatic glycogen synthesis and glycogenolysis.
Taking the above mentioned into account, differences in the postprandial hepatic glycogen metabolism in diabetic populations (Hundal et al. 2000; Bischof et al. 2001; Krssak et al. 2004) could have been caused by a decreased response in the portal insulin:glucagon ratio. In order to evaluate hepatic glucose metabolism independently of these T2DM associated alterations in postprandial metabolic and hormonal responses, we have assessed glycogen metabolism, as well as rates of EGP and whole body glucose disposal-matched conditions of hyperglycaemia, portal vein insulin:glucagon ratios and similar plasma FFA concentrations (Krssak et al. 2004). Nevertheless, ~54 % reduced rates of net hepatic glycogen synthesis were still observed in T2DM (Figure 11.13). Detailed analysis of the responsive fluxes tic m atm
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