Sodium Elevates the Plasma Glucose Response to Glucose Ingestion in Man*

Abstract
Active transport of glucose across the intestinal mucosa is dependent upon the presence of sodium in the gut lumen. While much information is available on the functional characteristics of this cotransport system, the role of sodium in the in vivo response to the ingestion of a glucose load has not been established. In the present study, two glucose solutions (87 g; Glucola), one containing 2.7 g sodium chloride (NaCl) and the other containing sufficient mannitol (87 mmol) to achieve the same osmolality, were administered orally to a group of 10 healthy subjects on separate days, and their plasma glucose responses were measured for 3.5 h after ingestion. Plasma glucose levels were significantly higher between 45–105 min of ingestion with NaCl than with mannitol, the mean difference being 19 mg/dl. The cumulative incremental glucose response was 7.3 ± 1.3 g/dl-210 min with NaCl and 5.7 ± 1.2 with mannitol (P < 0.01). The plasma insulin response to glucose plus NaCl was also significantly (P < 0.05) heightened during the same time period. The observed increase in plasma glucose levels after glucose plus NaCl was not due to reduced removal of glucose from the peripheral circulation, because the rates of glucose disappearance from plasma (measured with [3H]3-glucose) were not different with the two glucose solutions (1115 ± 88 vs. 1058 ± 98 mg/kg·210 min). Enhanced glucose absorption from the gut was therefore the likely cause of the greater glycemic response. In support of this, plasma levels of gastric inhibitory polypeptide, which are known to rise in a dose-dependent fashion after oral glucose, were significantly higher between 45–105 min after the ingestion of glucose plus NaCl than after glucose plus mannitol, as were the integrated gastric inhibitory polypeptide responses (206 ± 26 vs. 179 ± 24 μg/ml·210 min; P < 0.025). Finally, an effect of mannitol per se on glucose absorption could be excluded because when the same glucose load, with or without 87 mmol mannitol, was given to another group of five subjects on separate days, the resulting plasma glucose and insulin concentration curves were similar. We conclude that the addition of NaCl enhances the glycemic response to glucose ingestion through facilitation of intestinal absorption.