Differential roles of splanchnic and peripheral tissues in the pathogenesis of impaired glucose tolerance.

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Abstract

To identify the mechanism(s) of the altered glucoregulatory response to a glucose load in subjects with impaired glucose tolerance, we selectively quantitated the components of net splanchnic glucose balance, i.e., splanchnic glucose uptake and hepatic glucose output, as well as peripheral glucose uptake, by combining [3-3H]glucose infusion with hepatic vein catheterization. After intravenous glucose infusion (6 mg X kg-1 X min-1 for 90 min), blood glucose rose to 172 +/- 7 mg/dl in controls and 232 +/- 13 mg/dl in subjects with impaired glucose tolerance (P less than 0.01). The response of plasma insulin did not differ significantly between the two groups (29 +/- 4 vs. 40 +/- 10 microU/ml at 90 min in control and in glucose intolerant subjects, respectively; P = NS). In both groups, glucose infusion caused the net splanchnic glucose balance to switch from the net output of the basal state to a net glucose uptake. However, this effect was more marked in subjects with impaired glucose tolerance than in control subjects (at 90 min: 2.83 +/- 0.53 vs. 1.60 +/- 0.18 mg X kg-1 X min-1, respectively: P less than 0.05). The different pattern of splanchnic glucose balance was entirely accounted for by a greater rise in splanchnic glucose uptake in the group of glucose intolerants , as the suppression of endogenous glucose output by the glucose load was practically complete in both groups. In contrast, glucose uptake by peripheral tissues increased considerably less in subjects with impaired glucose tolerance than in controls (2.2-2.6 vs 3.6-4.1 mg X kg-1 X min-1, respectively, between 60 and 90 min; P less than 0.01-0.001). Furthermore, a net splanchnic lactate uptake was present in the basal state, which was inhibited by the glucose load and switched to a comparable net lactate output in both groups. These results indicate that the mechanism responsible for the altered glucoregulation in subjects with impaired glucose tolerance resides entirely in the peripheral tissues whose ability to dispose of a glucose load is drastically reduced. On the other hand, no defect is detectable in any of the explored mechanisms regulating splanchnic glucose metabolism during the disposal of an exogenous glucose load.

Authors

L Saccà, G Orofino, A Petrone, C Vigorito