Human intestinal potential difference: recording method and biophysical implications.

1. The transmural electrical potential difference (PD) of the intact human small intestine was recorded with close attention to electrical symmetry, shielding from electro-magnetic waves and correction for junction potentials. 2. The PD is -12 mV (mucosa-negative) in the fasting jejunum and ileum and does not change during perfusion with isotonic NaCl. 3. Absorption of Na and Cl appears to be non-electrogenic and the 'resting' PD is probably generated by active anion secretion of fasting intestinal contents. 4. Diffusion potentials during isotonic D-mannitol perfusion indicated higher cation selectivity in the ileum than in the jejunum. 5. The calculated contribution of a free-solution path to total paracellular permeability is 55% in the jejunum but only 15% in the ileum. 6. No 'streaming' potential was detected during osmotic water flow, suggesting that the cation-selectivity of the channels is temporarily inactivated during dilatation of the lateral intercellular space.

Transport of monosaccharides by the small intestine of genetically diabetic mice.

Small intestinal absorptive function was investigated in genetically diabetic mouse model (C57 BL/KSJ dbm) in order to determine the long-term effects of genetic and uncontrolled diabetes mellitus on intestinal function. Initial rates of uptake of nonmetabolizable glucose analogs, beta-methyl-D-glucoside and 3-O-methyl-D-glucose were determined in diabetic mice and their littermate controls using everted sacs from proximal and distal halves of the intestine. In addition, intestinal weight, intestinal length, mucosal protein, and DNA were measured. There were no significant differences between controls and diabetics in rates of uptake by either proximal or distal segments. Kinetic characteristics of uptake, Km and Vmax, were similar in controls and diabetics. These results clearly demonstrate that intestinal transport of monosaccharides is not altered in genetic diabetes, and therefore are in contrast to augmented transport reported in the early phase of drug-induced diabetes but similar to the results observed in chronic drug-induced diabetes. However, diabetic mice exhibited stimulated intestinal growth similar to rats with chronic drug-induced diabetes.

Glucagon effects on the human small intestine.

In healthy volunteers, the effects of intravenously administered glucagon on small intestinal function was investigated. Bolus doses resulting in plasma glucagon concentrations of greater than 800 pg/ml (5 min after injection) abolished jejunal contractions for 4.4 +/- 0.4 (SEM) min after a latency period of 49 +/- 4 sec. During continuous intravenous glucagon infusion, jejunal dilatation and increase in mean transit time (MTT) occurred at plasma levels greater than 720 pg/ml, while inhibition of water and electrolyte absorption was observed only with plasma glucagon concentrations of 1760 +/- 114 pg/ml. Under these conditions, the propulsion of fasting intestinal contents was slowed without change in flow rate. The observed effects cannot be attributed to the simultaneously occurring rise in plasma insulin and glucose concentrations. Short-term increases in circulating glucagon concentration inhibit intestinal tone, contractions, and propulsion with only a minor effect on water and electrolyte absorption limited to a narrow concentration range of plasma glucagon. Neither effect occurs at glucagon levels likely to occur under physiologic concentrations. The latency period preceding the abolition of jejunal contractions suggests that glucagon does not act directly on intestinal smooth muscle cells.

Effect of insulin, glucose, and controlled diabetes mellitus on human jejunal function.

The effects of serum insulin concentration, serum glucose concentration, and of insulin-dependent diabetes mellitus on human jejunal glucose, Na, and H2O absorption were assessed. Triple-lumen perfusion studies were carried out in 20 nondiabetic and 9 insulin-requiring diabetic male volunteers. In seven normal subjects, sequential elevation of serum insulin concentrations from 20 muU/ml to 50 and 100 muU/ml for 2 h each, with maintenance of constant serum glucose levels, failed to significantly alter glucose, Na, and H2O absorption. Absorption of glucose, Na, and H2O was similar when the serum glucose concentration was maintained at 125 and at 250 mg/100 ml. Glucose absorption results during 26 perfusion studies in 20 control subjects were compared with results obtained during 20 perfusion studies in 9 diabetic subjects. Glucose concentrations in isotonic perfusates were 25, 40, or 75 mM. Na and H2O absorption rates were similar in both groups. Regression lines relating glucose load or geometric mean study segment glucose concentration to glucose absorption were also comparable. These results indicate that insulin-requiring diabetics absorb glucose, Na, and H2O normally.

Lower esophageal sphincter responses to enteric hormones in two patients with Zollinger-Ellison syndrome.

The effect of exogenous glucagon and secretin on resting lower esophageal sphincter (LES) tone during endogenous hypergastrinemia was studied in 2 patients with proven Zollinger-Ellison Syndrome (ZES). Intravenous glucagon and in one patient secretin, in dosages which decrease LES pressure in normals during LES stimulation by exogenous gastrin, caused a decrease in resting LES pressure in the ZES patients. This drop in LES tone occurred both during concomitant serum gastrin rise caused by secretin and serum gastrin decline caused by glucagon. This finding suggests that the action of secretin on LES pressure may be independent on endogenous gastrin, while the glucagon effect on LES tone may be mediated through gastrin.

Effect of antidiuretic hormone on human small intestinal water and solute transport.

The effect of i.v. Pitressin (ADH) in a dose of 1 U/hr on permeability characteristics and on absorptive capacity of the normal human small intestine was investigated. The method of continuous intestinal perfusion was employed with polyethylene glycol 4000 as a nonabsorbable marker. Unidirectional flux rates of Na and H(2)O were calculated from the disappearance of (22)Na and of (3)HOH from isotonic saline solution within the intestinal lumen. Each study consisted of two successive perfusion periods: one while the subject was hydrated, the other during ADH infusion or while the subject was dehydrated. Water and sodium absorption from isotonic NaCl occurred in the hydrated state and was abolished by ADH as well as by dehydration in the jejunum. In some instances, net gain of water and sodium in the lumen occurred. In the ileum, ADH and dehydration caused a decrease in water and sodium absorption rate. By contrast, unidirectional flux into the intestinal lumen of water and sodium, as well as dextrose and D-xylose diffusion, remained unchanged by ADH. During perfusions with hypertonic urea solutions the rates of sodium and water entry into the intestine were greatly increased during i.v. ADH infusion, whereas urea loss from the study segment remained constant. ADH in the dosage used did not affect human intestinal motility. The results suggest that circulating ADH in physiologic concentrations affects the small intestine in one of two ways: increased secretion of water and salt into the lumen or direct interference with the active sodium transport mechanism.