Catja Johansson

Gastrointestinal function in obesity : motility, secretion, and absorption following a liquid test meal

Digestive responses to a 300-mL liquid fat-rich meal (432 kcal) in a group of massively obese patients were compared with those observed in a group of healthy lean subjects of variable body weight. Gastric and intestinal propulsion, digestive secretions, and absorption in the proximal 70 cm of intestine were measured using a multiple-marker dilution method. The average gastric emptying of energy, acid, volumes, and meal marker were similar in the two groups 80 minutes after intake, justifying a comparison of intestinal processing of the meal. Compared with lean subjects, the obese subjects responded with less pancreatic secretion (P less than .05) and gallbladder emptying, but absorbed a larger proportion of the emptied energy in the test segment (P less than .01) during a similar or shorter transit time. In addition, when the entire meals were compared, the obese group generally absorbed the test meal more effectively and rapidly in the upper part of the intestine. As a consequence, the flow volumes at the exit of the test segment were lower (P less than .05), and less of the test meal was propulsed to distal parts of the intestine. In the lean subjects, the body weight or height correlated positively with the gastric emptying rate, peak gastric acid output, and pancreatic responses, and negatively with (P less than .05) the segment transit time. The taller the subject, the greater the proportion of the meal which was rapidly propulsed unabsorbed to lower parts of the intestine, indicating that a large intestinal area was exposed for rapid energy uptake. No such correlations were observed in the obese group.

Plasma concentrations of regulatory peptides in obseity following modified sham feeding (MSF) and a liquid test meal

Plasma concentrations of regulatory peptides were monitored in groups of obese and normal-weight subjects following modified sham feeding and a liquid fatty meal. Following modified sham feeding a significant increase in immunoreactive cholecystokinin (CCK) in plasma was recorded in both groups. In the obese subjects, however, the concentrations following sham feeding were significantly lower than in normal-weight subjects, and the initial part of the response was negative. Basal and modified sham feeding stimulated immunoreactive pancreatic polypeptide (PP) concentrations in plasma did not differ between the groups. After the liquid fatty meal plasma CCK concentrations increased similarly in both groups. In contrast immunoreactive neurotensin and somatostatin concentrations following the meal were lower in the obese group, and a changed concentration-time pattern for somatostatin was observed in the obese group. Postprandial concentrations of PP and immunoreactive gastrin were not different in the groups. The results indicate that the plasma concentration patterns of CCK, somatostatin and NT are disarranged in obesity. The changes may promote rapid propulsion and absorption of ingested food, and facilitate deposition of fat in adipose tissue in obesity and thus may be of pathophysiological importance.

Effects of Somatostatin on Gastrointestinal Propagation and Absorption of Oral Glucose in Man

The effects of i.v. somatostatin, 6.0–0.05 μg · min-1, on the gastric emptying and on the transit times and glucose absorption in the proximal 70 cm of the small bowel after 75 g of oral glucose were examined in healthy subjects with a multiple-marker dilution method. In the controls the stomach emptied the hypertonic glucose solution in 3 h and 48 ± 4 g of glucose was absorbed in the intestinal test segment. Approximately even proportions were absorbed from the emptied glucose portions throughout the experiments; variations were caused by the varying transit time, the absorption being more complete the longer the time to transit the segment. Somatostatin, started 20 min before oral glucose and infused for 1 or 2 h, prolonged dose-dependently the transit time. A maximal prolongation from 15 ± 2 min in the controls to 55 ± 7 min (p -1, and 0.05 μg · min-1 somatostatin gave a significant twofold slowing. The inhibition of the intestinal motility persisted in the postinfusion period and was followed by a late sudden acceleration of the propagation speed. The gastric emptying rate was reduced by somatostatin, but the inhibition was slowly established and of marginal consequences for the absorption. 2-Hour infusions of more than 1.5 μg · min-1 delayed the complete emptying. Somatostatin reduced dose-dependently the glucose absorption rate in the segment. In the controls the absorption rate of 9.5 ± 1.4% · min-1 of transit decreased to 4.2 ± 0.7% min-1 (p -1 and to 2.6 ± 0.1 % · min-1 (p -1 of somatostatin and was further lowered by higher doses. The lower effectiveness was compensated by the prolonged transit times so that the totally absorbed glucose in the segment approached the control value. An absolute reduction was only recorded in early phases of the experiments before the transit was slowed and it seems to result in spite of prolonged transit from infusion rates of 1.5 μg · min-1 or more somatostatin. Dose-related side effects from the digestive tract and due to hypoglycemia in the late postinfusion period were common with infusion rates exceeding 0.5 μg · min-1. The study shows that exogenous somatostatin delays and evens out the uptake of oral glucose in the proximal small bowel by dose-dependent inhibitory effects on the gastrointestinal motility and reductions of the glucose absorption rate. The effects could be produced by somatostatin doses a hundred times lower than previously tested for effects in the human gastrointestinal tract.

Effects of Graded Doses of Somatostatin on Gallbladder Emptying and Pancreatic Enzyme Output after Oral Glucose in Man

Effects of intravenous somatostatin on the secretion, motility and absorption in the upper gastrointestinal tract after 75 g oral glucose were examined in healthy subjects with a quantitative multiple indicator dilution method. This report deals with the effects on the gallbladder emptying and the pancreatic enzyme output. Intake of a hypertonic glucose solution induces rapid gallbladder emptying. After early peaks, both biliary and pancreatic enzyme outputs remain at a steady lower level to the end. Somatostatin, started 20 min before the oral load, inhibited dose-dependently the gallbladder emptying and pancreatic enzyme secretion. A maximal inhibition was attained by 1.5 microgram . min-1, and 0.05 microgram . min-1 somatostatin gave a significant 40% reduction. The inhibition persisted in the postinfusion period and was followed by delayed rebound outputs. The gallbladder emptying was completely arrested for variable periods of time, but the pancreatic enzyme secretion was never totally blocked. The promptly established arrest of the gallbladder differed from the slowly initiated inhibition of the gastric and intestinal propulsion. It is proposed that the multiple ways of action of somatostatin and different stimulatory levels contribute to the discrepancies. The study shows that somatostatin induces dose-dependent, long-lasting inhibitions of the biliary and pancreatic responses to oral glucose. The minimal effective dose was a hundred times lower than the dose tested in previous studies in man.

HCl-stimulated duodenal HCO3- secretion in conscious rat. Interactions among VIP, nicotinic receptor mechanisms, and prostaglandins.

Using an isolated loop of the proximal duodenum of conscious rats, the role of vasoactive intestinal peptide (VIP) in the duodenal HCO3− response to HCl was examined, especially interactions with participating cholinoceptor mechanisms and prostaglandins. A 5-min perfusion with 150 mmol/liter HCl increased luminal VIP during 3 hr, with a peak output during and immediately after the acid challenge. The HCl-stimulated output was unaffected by atropine and hexamethonium, but was augmented by indomethacin from 13.6 (9.5–17.8) to 39 (20–85) fmol/cm/min. The HCO3− secretion in response to graded doses of intravenous VIP (0.00625–6 nmol/kg/30 min) was dose-dependent to maximally 33.5±10.5 µmol/cm/hr. The HCO3− secretion during a single intravenous infusion of VIP (12 nmol/kg/hr), 13.9±4.2 µmol/cm/hr, was unchanged by atropine, reduced to 10.0±3.5 µmol/cm/hr by hexamethonium, and augmented to 18.9±4.7 µmol/cm/hr by indomethacin. Exogenous VIP did not change the basal luminal output of PGE2; neither did exogenous PGE2 nor indomethacin affect the basal luminal output of VIP. HCl-induced increases in luminal outputs of VIP, substance P, and neurokinin A (the two latter with unknown roles) were differentially affected by atropine, hexamethonium, and indomethacin, indicating that the acid challenge released the peptides through controlled mechanisms. In conclusion, in the duodenal HCO3− response to luminal HCl, VIP may have a stimulatory role, which partially depends on nicotinic, but not on muscarinic cholinoceptor mechanisms, and which is negatively modulated by prostaglandins.