13C-carbohydrate breath tests: impact of physical activity on the rate-limiting step in lactose utilization.

BACKGROUND: 13CO2 breath tests can be used to monitor carbohydrate digestion in the small intestine. However, after ingestion of 13C-substrates, 13CO2 excretion in breath originates from two sources: a digestive/oxidative fraction, derived from the small intestine, and a fermentation fraction, derived from undigested substrate spill-over in the colon. In this study, the determinants of the digestive/oxidative fraction were analysed in order to improve the sensitivity/specificity of the 13C-carbohydrate breath tests. METHODS: 13C-carbohydrate breath tests were performed in healthy adults using 13C-lactose, pre-digested 13C-lactose, 13C-glucose, and 13C-galactose as substrates. The effect of exercise (bicycling, 50 W), increasing the metabolism of digested/absorbed substrate, on the outcome of the test was analysed. RESULTS: In rest, no difference was observed in the 4-h cumulative percentage dose recovered in breath (4-h cPDR) after administration of glucose, pre-digested lactose, and lactose, which were 20.3 +/- 4.5%, 19.2 +/- 5.5%, and 19.9 +/- 4.9%, respectively. The 13CO2 excretion rate after 13C-galactose consumption was significantly slower than after 13C-glucose consumption. Exercise increased 4-h cPDR of 13C-glucose significantly: 76.0 +/- 1.0% vs. 22.7 +/- 2.3%. This effect was also observed using 13C-lactose as substrate: 66.1 +/- 6.2% vs. 19.6 +/- 3.9%. One subject had non-symptomatic lactose maldigestion indicated by a positive H2 breath test. The 13CO2 breath test of this subject in rest was indistinguishable from that of the others (4-h cPDR 16.6 vs. 19.6 +/- 3.9%), whereas the test was clearly indicative during exercise (4-h cPDR 20.5 vs. 66.1 +/- 6.2%). CONCLUSION: In healthy volunteers in rest, glucose oxidation is the rate-limiting step in lactose conversion into 13CO2. Increase of metabolism (for instance, by exercise) can shift this step to intestinal hydrolysis of lactose, making the 13C-lactose breath test more sensitive.

Insulin levels after portal and systemic insulin infusion differ in a dose-dependent fashion.

The role of the liver in the regulation of systemic insulin levels is not well understood. The reported extraction rates vary between 0 to 85%, and extraction of a constant fraction of 50% of the portally delivered insulin is generally assumed. In the present study, we have investigated the role of the liver in the regulation of systemic insulin levels in the normal rat. Insulin was infused into the portal vein of conscious and freely moving rats in doses of 20, 40, 80 pmol/min during 15 min to mimic the gradual release of insulin by the native endocrine rat pancreas. The profiles of plasma insulin and glucose levels in the systemic circulation were compared to those obtained after direct infusion into the systemic circulation. The effect of intraportal and direct systemic infusion on plasma insulin and blood glucose levels were virtually similar where 20 pmol/min was applied. But, these effects were different if the dose was 40 pmol/min, and this difference increased when the dose was increased to 80 pmol/min, since hypoglycemia was less severe and normoglycemia was restored more rapidly with portal than with systemic infusion. Thus, our results show that the fraction of intraportally infused insulin reaching the systemic circulation decreases with higher doses of insulin. This suggests that the liver contains adaptable mechanisms to reduce the systemic insulin levels.

Kinetics of intraperitoneally infused insulin in rats. Functional implications for the bioartificial pancreas.

Intraperitoneal transplantation of encapsulated islets can restore normoglycemia in diabetic recipients but not normal glucose tolerance nor normal insulin responses to a physiological stimulus. This study investigates whether the intraperitoneal implantation site as such contributes to the interference with optimal transport kinetics between the islets and the bloodstream. Insulin was infused into the peritoneal cavity of conscious and freely moving rats in doses of 20, 40, and 80 pmol.l-1.min-1 during 15 min, to mimic the gradual release of insulin from an encapsulated, i.e., a nonvascularized, islet graft. With 20 pmol.l-1.min-1, we observed virtually no rise of insulin levels, and it took 30 min until glucose levels had dropped significantly. With 40 and 80 pmol.l-1.min-1 insulin infusions, there was a dose-dependent rise of insulin and decrease of glucose levels. When compared with intraportal infusions with the same insulin dosages, however, they were strongly delayed and reduced as well as prolonged. Similar results were obtained when inulin instead of insulin was intraperitoneally infused, with indicates that the transport of insulin from the peritoneal cavity to the bloodstream is mainly by passive diffusion. With a view on the clinical efficacy of the bioartificial pancreas, our findings indicate that we should focus on finding or creating a transplantation site that, more than the unmodified peritoneal cavity, permits close contact between the bloodstream and the encapsulated islet tissue.