The effect of DPP-4 inhibition with sitagliptin on incretin secretion and on fasting and postprandial glucose turnover in subjects with impaired fasting glucose.

OBJECTIVE: Low glucagon-like peptide-1 (GLP-1) concentrations have been observed in impaired fasting glucose (IFG). It is uncertain whether these abnormalities contribute directly to the pathogenesis of IFG and impaired glucose tolerance. Dipeptidyl peptidase-4 (DPP-4) inhibitors raise incretin hormone concentrations enabling an examination of their effects on glucose turnover in IFG. RESEARCH DESIGN AND METHODS: We studied 22 subjects with IFG using a double-blinded, placebo-controlled, parallel-group design. At the time of enrollment, subjects ate a standardized meal labelled with [1-(13)C]-glucose. Infused [6-(3)H] glucose enabled measurement of systemic meal appearance (MRa). Infused [6,6-(2)H(2)] glucose enabled measurement of endogenous glucose production (EGP) and glucose disappearance (Rd). Subsequently, subjects were randomized to 100 mg of sitagliptin daily or placebo. After an 8-week treatment period, the mixed meal was repeated. RESULTS: As expected, subjects with IFG who received placebo did not experience any change in glucose concentrations. Despite raising intact GLP-1 concentrations, treatment with sitagliptin did not alter either fasting or postprandial glucose, insulin or C-peptide concentrations. Postprandial EGP (18.1 +/- 0.7 vs 17.6 +/- 0.8 micromol/kg per min, P = 0.53), Rd (55.6 +/- 4.3 vs 58.9 +/- 3.3 micromol/kg per min, P = 0.47) and MRa (6639 +/- 377 vs 6581 +/- 316 micromol/kg per 6 h, P = 0.85) were unchanged. Sitagliptin was associated with decreased total GLP-1 implying decreased incretin secretion. CONCLUSIONS: DPP-4 inhibition did not alter fasting or postprandial glucose turnover in people with IFG. Low incretin concentrations are unlikely to be involved in the pathogenesis of IFG

Transport of dissolved Si from soil to river: a conceptual mechanistic model

This paper reviews the processes which determine the concentrations of dissolved silicon (DSi) in soil water and proposes a mechanistic model for understanding the transport of Si through a typical podzol soil to the river. DSi present in natural waters originates from the dissolution of mineral and amorphous Si sources in the soil. However, the DSi concentration in natural waters will be dependent on both dissolution and deposition/precipitation processes. The net DSi export is controlled by soil composition like (mineralogy and saturated porosity) as well as water composition (pH, concentrations of organic acids, CO2 and electrolytes). These state variables together with production, polymerization and adsorption equations constitute a mechanistic framework determining DSi concentrations. For a typical soil profile in a temperate climate, we discuss how the values of these key controls differ in each soil horizon and how it influences the DSi transport. Additionally, the impact of external forcings such as seasonal climatic variations and land use, is evaluated. This model is a first step to better understand Si transport processes in soils and should be further validated with field measurements