The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are degraded by dipeptidyl peptidase IV (DPP IV), thereby losing insulinotropic activity. DPP IV inhibition reduces exogenous GLP-1 degradation, but the extent of endogenous incretin protection has not been fully assessed, largely because suitable assays which distinguish between intact and degraded peptides have been unavailable. Using newly developed assays for intact GLP-1 and GIP, the effect of DPP IV inhibition on incretin hormone metabolism was examined.Conscious dogs were given NVP-DPP728, a specific DPP IV inhibitor, at a dose that inhibited over 90% of plasma DPP IV for the first 90 min following treatment. Total and intact incretin concentrations increased (P<0·0001) following a mixed meal, but on control days (vehicle infusion), intact peptide concentrations were lower (P<0·01) than total peptide concentrations (22·6 1·2% intact GIP; 10·1 0·4% intact GLP-1).Following inhibitor treatment, the proportion of intact peptide increased (92·5 4·3% intact GIP, P<0·0001; 99·0 22·6% intact GLP-1, P<0·02). Active (intact) incretins increased after NVP-DPP728 (from 4797 364 to 10 649 106 pM min for GIP, P<0·03; from 646 134 to 2822 528 pM min for GLP-1, P<0·05). In contrast, total incretins fell (from 21 632 654 to 12 084 1723 pM min for GIP, P<0·002; from 5145 677 to 3060 601 pM min for GLP-1, P<0·05). Plasma glucose, insulin and glucagon concentrations were unaltered by the inhibitor.We have concluded that DPP IV inhibition with NVP-DPP728 prevents N-terminal degradation of endogenous incretins in vivo, resulting in increased plasma concentrations of intact, biologically active GIP and GLP-1. Total incretin secretion was reduced by DPP IV inhibition, suggesting the possibility of a feedback mechanism.

Introduction  Metabolism cages play a pivotal role in nutritional science as they are often used in experiments to determine nutrient requirements of animals, dietary nutrient digestibilities, endogenous excretions, glomerular filtration rates, mineral balance, 24‐h urinary excretion rates, etc. Such cages are a convenient way to obtain accurate data on the amount and frequency of excreta produced by animals. The accuracy of the procedures and equipment used for the measurement of excreta production, however, is often neglected, casting doubt on the results obtained. Recently, Wamberg et al. (1996b) showed that the recovery of urine collection from mink (Mustela vison) housed in a standard metabolism cage ranged from 68 to 88% in the fed state and 62–78% in the fasted state. This magnitude of under‐collection of urine will have a significant impact on data where quantitative urine collection is paramount, such as endogenous urinary excretions, and 24‐h urinary excretion rates. The main reason for the incomplete collection of urine in mink was attributed to the cross‐contamination of faeces with urine (Wamberg et al. 1996b). The domestic cat is a strict carnivore and has been noted to excrete relatively concentrated urine (Chew 1965; Anderson 1982). Under‐collection of urine, therefore, has a major impact on the measurement of excretion rates of urinary constituents and any subsequent derived data. The cat, furthermore, has been noted for oliguria, anuria and spraying of urine while held in metabolism cages (Worden et al. 1960; Klatt et al. 1975; Matandos and Franz 1980; Russo et al. 1986), making the domestic cat a difficult animal from which to collect excreta quantitatively. The main objective of this study was to validate quantitative urine collection from cats housed in specially designed metabolism cages fitted with a urine/faeces collection system when fed a nutritionally balanced diet and in the feed‐restricted state. Furthermore, the accuracy of water balance measurements using the metabolism cages and urine/faeces collection system was assessed in adult cats.

Body fluid regulation depends on regulation of renal excretion. This includes a fast vasopressin-mediated water-retaining mechanism, and slower, complex sodium-retaining systems dominated by the renin-angiotensin aldosterone cascade. The sensory mechanisms of sodium control are not identified; effectors may include renal arterial pressure, renal reflexes, extrarenal hormones and other regulatory factors. Since the pioneering work of Guyton more than three decades ago, pressure natriuresis has been in focus. Dissociations between sodium excretion and blood pressure are explained as conditions where regulatory performance exceeds the precision of the measurements. It is inherent to the concept, however, that sudden transition from low to high sodium intake elicits an arterial pressure increase, which is reversed by the pressure natriuresis mechanism. However, such transitions elicit parallel changes in extracellular fluid volume thereby activating volume receptors. Recently we studied the orchestration of sodium homeostasis by chronic and acute sodium loading in normal humans and trained dogs. Small increases in arterial blood pressure are easily generated by acute sodium loading, and dogs appear more sensitive than humans. However, with suitable loading procedures it is possible -also acutely -to augment renal sodium excretion by at least one order of magnitude without any change in arterial pressure whatsoever. Although pressure natriuresis is a powerful mechanism capable of overriding any other controller, it seems possible that it is not operative under normal conditions. Consequently, it is suggested that physiological control of sodium excretion is neurohumoral based on extracellular volume with neural control of renin system activity as an essential component.

Dietary benzoic acid (BA) supplementation causes a pronounced reduction in urinary pH but only small changes in blood pH. The present study aimed to investigate the portal absorption profile, hepatic metabolism of BA, and renal excretion of hippuric acid (HA) underlying the relatively small impact of BA on systemic acid-base status. Eight growing pigs (BW = 63 +/- 1 kg at sampling) fitted with permanent indwelling catheters in the abdominal aorta, hepatic portal vein, hepatic vein, and mesenteric vein were allocated to 4 sampling blocks and randomly assigned to control (CON; nonsupplemented diet) or BA supplementation (B; control diet + 1% BA top-dressed). Feed intake was restricted to 3.6% of BW and the ration divided into 3 equally sized meals offered at 8-h intervals. Blood pH (7.465 and 7.486 +/- 0.004) and urinary pH (4.99 and 7.01 +/- 0.09) were less (P = 0.03 and P < 0.01) in B compared with CON. The arterial concentration, net portal flux, and net hepatic uptake of BA increased (P < 0.01) in B compared with CON. The net portal flux of BA increased (P < 0.01) after feeding with B, but remained positive (P < 0.01) at all sampling times (n = 8). Recovery of dietary BA as increased net portal flux and hepatic uptake of BA was 87 +/- 5% and 89 +/- 15%, respectively. The recovery of dietary BA as urinary excretion of BA and HA was 0.08 +/- 0.02% and 85 +/- 7%, respectively. It is concluded that the small impact of BA supplementation on systemic acid-base status was caused by a protracted BA absorption and efficient hepatic extraction and glycine conjugation in combination with efficient renal clearance of HA. Together, these physiological mechanisms prevented major BA and HA accumulation in body fluids.