Elliot Weser

Studies of Small Bowel Adaptation After Intestinal Resection in the Rat

Fasting rats were killed 5 to 6 weeks after a 50-cm resection of either proximal or distal small bowel or sham operation. Remaining intestinal segments appeared increased in both thickness and diameter. The mean villous height was greater in proximal and distal bowel remnants of resected animals than in comparable segments of sham animals of the same age and weight. The number of epithelial cells per μ of villous surface increased in proximal and distal villi. Lactase, sucrase, and maltase activities were significantly lower in homogenates of both whole mucosa and isolated villous epithelial cells collected from proximal remnants. With the exception of sucrase, disaccharidase activity was also significantly lower in whole mucosa and isolated epithelial cells collected from distal remnants. Isolated epithelial cells collected from proximal and distal remnants were incubated with C14-labeled glucose and C14-labeled leucine. The ratios of glucose or leucine counts per min per ml of cell water to counts per min per ml of incubation medium indicated active transport and were equal to ratios obtained from cells collected from control segments. However, when uptake of glucose and leucine was determined as a function of the number of cells, the net transport of both substrates was reduced in cells collected from the distal remnant. Glucose transport in everted gut sacs prepared from proximal remnants was significantly less than control segments. In the early steady state after small bowel resection, the remaining segment shows hyperplasia with an increase in the number of epithelial cells lining the villous surface. These presumably less mature and smaller cells have diminished disaccharidase and transport activity.

Metabolism of Circulating Disaccharides in Man and the Rat

The metabolism of circulating disaccharides was studied in adult humans and rats. After iv infusions of 10 g of either lactose, sucrose, or maltose in four adults, no rise in blood glucose was noted. A mean of 8.7+/-1.89 g of the lactose and 6.3+/-1.39 g of the sucrose was excreted in the 24-hour urine sample. Only 0.11+/-0.03 g of the infused maltose was recovered in the urine, suggesting that the maltose was metabolized.After injection of (14)C-labeled lactose and sucrose in rats, 6.2+/-2.7 and 7.6+/-2.4%, respectively, was oxidized to (14)CO(2) in 24 hours; 62.1+/-13.5 and 68.4+/-10.8% of the respective disaccharides was excreted into the urine. Conversely, after injection of (14)C-labeled maltose 54.6+/-7.0% was oxidized to (14)CO(2) and 4.8+/-3.9% excreted in the urine. The per cent of maltose oxidized to CO(2) was similar to that of glucose. In addition to small intestinal mucosa, homogenates of rat kidney, brain, and liver as well as serum were found to have measurable maltase activities. The role of these tissue maltases in the metabolism of circulating maltose and maltosyloligosaccharides is discussed.

Lactase Deficiency in Patients with the Irritable-Colon Syndrome

SEVERAL recent studies suggest that lactase deficiency is common in the adult. It may be present as an isolated enzyme defect1 2 3 4 5 or may accompany organic disease of the small bowel.6 7 8 The ...

The metabolism of circulating maltose in man

The utilization of circulating maltose was compared to that of glucose in six normal fasting subjects after intravenous injection of 25 g of either sugar. Blood samples were obtained over a 2 hr period and were assayed for free fatty acids (FFA), insulin, glucose, and total reducing substances. Urine was collected for 2 hr after maltose administration and assayed enzymatically for glucose and maltose. Blood glucose concentrations did not increase after maltose infusion, although a significant rise in total reducing substances was noted, indicating the presence of this disaccharide in the blood. Less than 3% of the administered maltose was excreted in the urine either as maltose or glucose. Initially, there was a fourfold increase in serum insulin concentration after glucose and a threefold increase after maltose infusion. Therefore, serum insulin concentrations gradually declined in a similar manner for both sugars. The plasma FFA at 15 min decreased 371 uEq/liter after glucose and 338 uEq/liter after maltose infusion. In other studies, 10 g maltose containing 5 muCi maltose-U-(14)C were injected into five human subjects and expired CO(2) collected for 6 hr. Maximal (14)CO(2) specific activity was noted at 170 min and a mean of 61.1% of the injected radioactivity was recovered as (14)CO(2). Less than 8% of the injected (14)C was excreted in the urine. These results indicate that maltose administered intravenously has similar metabolic effects when compared to glucose, and may be efficiently utilized as a carbohydrate substrate. The oxidation of intravenously administered maltose-U(14)C to (14)CO(2) demonstrates that circulating maltose is readily metabolized. A solution of maltose could provide twice the mass of sugar (and of calories) per milliliter as an equimolar solution of glucose. Parenterally administered maltose may be of clinical value and should be further studied.

Hyperplasia of the Gastric Glands after Small Bowel Resection in the Rat

One month and 7 months after proximal or distal small bowel resection, adult Sprague-Dawley rats show a significant increase in the number of epithelial cells of the gastric glands (total cells, P

LACTOSURIA AND LACTASE DEFICIENCY IN ADULT CELIAC DISEASE.

Summary The 5-hr urinary lactose excretion after a 25 g. oral load was measured in 16 patients with adult celiac disease and 18 normal controls. The normal mean excretion was 54 ± 23 mg. In five normal subjects the mean intestinal lactase and invertase activities were 32.0 ± 13.3 and 58.4 ± 25.7 units, respectively. Ten celiac patients on inadequate gluten restriction excreted a mean of 215 ± 80 mg of lactose ( P P P Five out of six adult celiac patients who adhered to strict, gluten-free diets for at least 2 years had normal lactose excretion, but in two the lactase and invertase activity remained low. All of these patients showed at least partial regeneration of the jejunal villi. Increased lactosuria was noted in two out of seven patients with other causes of malabsorption. Lactase activity was measured in five and found to be as low as in the celiac patients on inadequate gluten restriction. It is suggested that the increased lactosuria found in adult celiac disease is related to an increase in mucosal permeability to lactose as well as to lactase deficiency.

Epithelial cell loss in remaining intestine after small bowel resection in the rat.

It is known that after small bowel resection, mucosal hyperplasia and increased cell turnover occur in the remaining intestine, particularly the ileum. At the end of their life span, epithelial cells are extruded into the bowel lumen. Comparative estimates of this cell loss may be obtained by collecting the DNA from a perfused gut segment. Male Sprague-Dawley rats underwent resection of 50 cm of proximal or distal small intestine or sham operation. One and six months after surgery, 50 cm of the remaining proximal or distal remnant were perfused with saline in vivo and the perfusate DNA was assayed. The DNA recovered from the perfusate of the distal remnant was at least twice as much as that from sham control segments. This was associated with comparable increases in mucosal weight, DNA, and protein concentration per centimeter of distal remnant. No significant changes were found in perfusate DNA recovered from proximal remnants. This correlated with minimal, if any, changes in mucosal weight, DNA, or protein concentration per centimeter of these remnants. Increased desquamation of epithelial cells may reflect the hyperplasia of intestinal mucosa after bowel resection. Recovery of intraluminal DNA may prove useful as an index of intestinal adaptation.

Stimulation of small bowel mucosal growth by midgut infusion of different sugars in rats maintained by total parenteral nutrition.

Summary Glucose infused into the gastrointestinal tract has been shown to prevent mucosal atrophy in animals maintained on total parenteral nutrition and to stimulate intestinal adaptation in remaining bowel after small bowel resection. In this study, several sugars absorbed by active and nonactive transport mechanisms were infused into mid-small bowel and compared for their effects on mucosal mass. Male Sprague-Dawley rats (240 g) were maintained on total parenteral nutrition for 7 days. The mid-small bowel was cannulated and continuously infused with a solution of either glucose (15%), fructose (15%). mannose (7.5%), mannitol (7.5%), or control (0.9% NaCl) at a rate of 2.4 ml/h. Similar studies were carried out after adding phlorizin (200 mg/100 ml) to the glucose and fructose solutions. After 7 days, rats were killed and the entire small bowel divided into eight equal segments. Segment weight, mucosal weight, DNA. and protein concentration per centimeter gut were measured. All rats gained in weight during the study period. Glucose and fructose midgut infusion significantly increased mucosal mass downstream from the site of infusion and also in remote proximal bowel segments. The addition of phlorizin to the glucose solution shifted the peak mucosal growth effects caudally. but did not have any effect when added to either fructose or control solutions. Despite lower concentrations, midgut infusion of mannose and mannitol also stimulated an increase in mucosal mass in proximal and distal segments. These studies indicate that midgut infusion of sugars absorbed by active transport (glucose), other carrier-mediated transport (fructose), and nonactive limited transport (mannose. mannitol) stimulates mucosal growth locally and in remotely located proximal intestine. Direct contact, absorption, osmolality, and humoral factors may all be involved in these responses.

Effect of Diverting Bile and Pancreatic Secretions into the Ileum on Small Bowel Mucosa in Rats Fed a Liquid Formula Diet

The long-term effects of diverting bile and pancreatic secretions directly into the ileum on small bowel mucosa was determined in rats fed a hydrolyzed liquid formula diet. Male Sprague-Dawley rats were divided into four experimental groups: duodenal papilla transplant-sham operation, transplantation of the duodenal papilla into the ileum, bile duct sham operation, and transplantation of the bile duct into the ileum. After 28 days, animals were killed, the same bowel removed, rinsed with cold isotonic saline, and divided into six segments (two jejunal segments and four ileal segments). The mucosa of each segment was weighed and assayed for DNA and protein concentration, and specific activity of sucrase and maltase. Bile and particularly pancreatic secretions diverted into the ileum stimulated local mucosal growth compared with their respective controls. The absence of pancreatic secretions from the jejunum also was associated with an increase in jejunal mucosal mass. Diverting pancreatic secretions into the ileum decreased ileal sucrase and maltase specific activity while the absence of both bile and pancreatic secretions from the jejunum increased jejunal sucrase specific activity. The results suggest that bile and pancreatic secretions entering the ileum are important factors in stimulating ileal mucosal hyperplasia while the absence of these secretions from the proximal intestine is associated with greater jejunal mucosal growth. The mechanisms regulating jejunal mucosal growth appear to be different than those influencing the ileum.

Effect of small bowel resection on the gastric mucosa in the rat.

Male Sprague-Dawley rats (120 to 130 gm), unoperated, sham-operated, and those with a 50% resection of the proximal small intestine, were studied after periods of 3, 6, 9, or 12 months. Differences in body weight and in the surface area, thickness, volume, and cellular content of the gastric mucosa between these three groups of animals were compared and statistically analyzed. After an initial loss in body weight, animals with small bowel resection and sham-operated animals attained weights equivalent to unoperated controls. Comparison of the groups for mucosal surface areas of the body of the stomachs showed no significant differences at the 3-, 6-, or 9-month periods. However, 12 months after surgery, the mucosal surface area of stomachs from resected animals was significantly greater than in corresponding controls. At 3, 6, and 9 months after resection, the thickness and volume of the gastric mucosa and the epithelial cell populations (parietal and nonparietal) of the gastric glands were significantly greater than in controls. However, at 12 months, there was no significant difference in any of these parameters between the controls and the experimental animals. The DNA content of the gastric mucosa was significantly greater for animals with small bowel resection than for corresponding controls at 1 and 6 months after surgery. It is concluded that hyperplasia of the gastric glands exists for at least 9 months after proximal small bowel resection in the rat. This hyperplastic response may be responsible for the previously observed (N Engl J Med 272:509-514, 1965; Surgery 65:292-297, 1969) gastric hypersecretion associated with extensive small bowel resection.