Turning our attention to hepatic glucose fluxes following a normal meal in type 1 and type 2 diabetic patients, studies have revealed significant alterations of hepatic glycogen storage (Figure 11.12), glycogen release and gluconeogenesis in both patient groups (Taylor et al.1996; Hundal et al. 2000; Bischof et al. 2001, 2002; Singhal et al. 2002; Krssak et al. 2004). A defect in hepatic glycogen storage was observed in glucokinase deficient maturity-onset diabetes of the young 2 (MODY-2) patients, in whom the impaired hepatic glucokinase activity is held responsible for a reduction in the contribution of glucose (the direct pathway) to hepatic glycogen synthesis (Velho et al. 1996). Lower glycogen synthesis (Bischof et al. 2001, 2002; Krssak et al. 2004) and unsatisfactory suppression of endogenous glucose production (Sinha et al. 2002; Krssak et al. 2004) contribute to postprandial hyperglycaemia in both pathologies. Increased gluconeogenesis is the key to postabsorptive hyperglycaemia in T2DM (Hundal et al. 2000). Therapeutic interventions by metformin in T2DM (Hundal et al. 2000) or by insulin controlled long-term near normoglycaemia in T1DM (Bischof et al. 2002) were able to at least partially eliminate these defects and restore normal hepatic glucose fluxes.
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