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Resection increases villus height and crypt depth of remaining intestine. We examined functional consequences of resection by measuring absorption of strontium and secretion of calcium and magnesium by proximal and distal segments remaining after resecting 70% of mid small intestine. Compared with the transected control group, resection decreased strontium absorption per unit weight of mucosa (specific absorption) in the proximal segment. The decreased specific absorption was compensated by increased mucosal growth in the resected group so that absorption per unit length of segment (per cm) was the same in both groups. Resection increased secretion of calcium and magnesium by 66% per unit weight of mucosa and by 145%/cm in the distal segment. Comparing proximal with distal segments in the resected group, secretion was greater in distal for calcium and in proximal for magnesium. Intestinal resection causes responses in absorption and secretion of divalent cations important in mineral homeostasis.

Because of the marked defect in calcium transport by the residual duodenum and ileum of the rat 10 days after 70% resection of mid-small intestine, we examined the calcium transport response by large intestine at this time. Although net cecal calcium absorption was decreased by one third in resected rats as compared with transected controls, total net cecal absorption was maintained because of the small growth response. Colonic calcium transport was the same in transected and resected groups, despite greater segment growth in the resected group. In comparison to the marked abnormality in calcium transport by the residual small intestine secondary to resection, the effect on the large intestine was minimal.

In rat with massive resection of mid-small intestine, calcium transport per segment, measured by in vivo perfusion 10 days after surgery, is decreased in duodenum and ileum but is the same in cecum and colon as compared with controls with transection and reanastomosis of mid-small intestine. To extend these findings, we measured balances of calcium, phosphorus, and fat from the 5th to 10th day after surgery and serum concentration of 1,25-dihydroxycholecalciferol on the 10th day after surgery in this experimental model. We found steatorrhea in the resected group, but balances of calcium and phosphorus and serum levels of 1,25-dihydroxycholecalciferol were the same in resected and control groups. We conclude that decreased transport defined by direct examination of membrane function may be undetectable when net transport is measured by balance. Calcium balance during early post-resection period provides no evidence for future calcium deficiency in this experimental model.

In prior studies, we examined kinetics of steady state in vivo transepithelial calcium transport in rat and hamster. The present studies related calcium uptake by the brush border to in vivo transport. We measured calcium uptake by brush border membrane vesicles from the two species. In the rat, our prior in vivo studies had shown that (a) calcium transport was mediated, (b) no nonmediated component was detectable, and (c) Vmax was 2.5 times greater in proximal than distal small intestine. In brush border membrane vesicles from the rat, Vmax for the saturable component of calcium uptake was again 2.5 times greater in proximal than distal intestine. Contrasting with in vivo studies, a major nonsaturable component was present in vesicles from proximal and distal small intestine. In the hamster, our previous in vivo studies had shown (1) both mediated and nonmediated components of calcium transport, (2) greater nonmediated transport in proximal than distal small intestines, and (3) Vmax for calcium transport twice as great in distal as in proximal small intestine. In the present study with brush border membrane vesicles from hamster, Vmax for saturable calcium transport was again twice as great in distal as in proximal small intestine. However, nonsaturable calcium transport rates relative to saturable rates were much greater with vesicles than in in vivo studies, and were greater in vesicles from distal than proximal small intestine. Since rates of saturable calcium uptake by brush border membrane vesicles parallel corresponding in vivo mediated transport rates, we conclude that the segmental rates of calcium transport in rat and hamster could be determined by brush border function.

The influence of pancreatic secretions on growth and brush-border enzyme activity, throughout the entire small intestine, was examined in the rat. Pancreatic secretions were excluded from the gut lumen by stapling the pancreatic ducts, without interruption of bile flow. The entire small intestine was studied as four segments; the duodenum and three distal segments of equal length. Weight of intestine and mucosa, and mucosal sucrase, isomaltase, lactase, and alkaline phosphatase activity were measured 10-15 days following pancreatic duct occlusion, or sham-operation. The duodenum of pancreatic duct-occluded animals exhibited significant hypertrophy. In general, specific and total disaccharidase activities were greater in duct-occluded animals than in controls throughout the intestine. The increase was more pronounced in distal than in proximal segments. The sucrase/isomaltase ratio was significantly greater in pancreatic duct-occluded animals than in controls in the two distal segments. Alkaline phosphatase activity was not affected by pancreatic duct occlusion. The greater relative increase of disaccharidase activities and sucrase/isomaltase activity ratios in the distal segments of duct-occluded animals, indicates a more important regulatory role of pancreatic enzymes in the distal small intestine. It is concluded that regulation of intestinal brush-border enzyme activity by pancreatic secretion is selective for enzyme and site as follows: disaccharidases, but not alkaline phosphatase, are regulated; the sucrase subunit of the sucrase/isomaltase complex is most sensitive to regulation, while lactase is least sensitive; and the regulatory effect on disaccharidases is greater in distal than in proximal intestine.

Uptake of calcium by brush-border membrane vesicles from rat small intestine is composed of saturable and nonsaturable components. We studied regulation of calcium uptake using the divalent cations strontium, a foreign ion that mimics calcium biologically and magnesium, a physiologically important ion that resembles calcium physically, although not biologically. Strontium present outside the vesicle inhibited saturable calcium uptake competitively, consistent with binding to the transporter at the same site as calcium. Strontium inside the vesicle accelerated saturable calcium uptake from the outside (countertransport), also consistent with binding to the same transporter site as calcium. Thus the calcium transporter shows functional characteristics of a mobile carrier. In the uptake medium (extracellular), magnesium was a noncompetitive inhibitor of saturable calcium transport, consistent with a regulatory role in calcium uptake by binding to the transporter at a locus other than that for calcium. Magnesium at 1 mM concentration inside the vesicle had no effect on saturable calcium uptake and a high concentrations functioned as a week uncompetitive inhibitor. Thus intracellular magnesium appears to have no major role in regulating saturable calcium uptake at the brush border of the enterocyte.

Structural and functional changes in the rat small intestine following localized hyperthermia were examined. In anaesthetized male Sprague-Dawley rats a 10 cm segment of mid-small intestine was temporarily exteriorized, suspended in a cup containing Krebs-Ringer solution, and either heated at 43.5 degrees C or sham-heated at 38 degrees C for 45 min. The intestinal segments were studied 1, 4, 7, 21 and 42 days later by histopathological examination, determination of wet weight, dry weight and gross segment area, and by measuring absorption of 15 mM D(+)-glucose containing 14C-labelled D(+)-glucose as a tracer. Intestinal glucose transport was assessed by two different techniques: the everted sac method (in vitro) and luminal perfusion-recirculation (in vivo). After 1 day, heated intestinal segments exhibited marked mucosal damage, consisting of loss of epithelial cells and destruction of villi. Re-epithelialization had occurred by day 4, but mucosal architecture remained abnormal throughout the observation period. Hyperthermia caused significant thickening of the intestinal wall: at 4 days the thickening was due to oedema, whereas at 42 days tissue mass per cm2 in heated segments had increased by approximately 53 per cent compared with sham-heated control segments. At 1 day, net glucose transport in vitro in heated segments was reduced to 20 per cent and the serosal/mucosal concentration ratio to 57 per cent of that of control segments. In vivo, glucose transport in heated intestine at 4 days was 45 per cent of that of controls. From 4 days on, glucose transport improved gradually, and at 42 days there was no significant difference between heated and sham-heated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied the early time-course of gastrin, somatostatin, and gut growth responses to 70% resection of mid-small intestine. Serum and antral gastrin increased by the 2nd day following resection and remained elevated for the 10-day period of study. Antral somatostatin remained unchanged, suggesting that the increase in gastrin was a selective antral response. Duodenum and ileum showed marked growth stimulation, which was progressive with time, and earlier and greater in duodenum. In contrast, gastric growth was unaffected. Thus, early responses to resection are characterized by specificity of gastrin, somatostatin, and growth effects.

Depressed somatic growth in the rat with streptozotocin diabetes is associated with greatly enhanced intestinal growth. In patients with diabetes mellitus, growth hormone is elevated. Therefore, we measured the association between gut growth and serum growth hormone in the streptozotocin-diabetic rat. At 10 days growth hormone did not differ in control, untreated diabetic and insulin-treated diabetic groups. At 20 days of diabetes, growth hormone was elevated in untreated diabetic groups, but depressed to control levels by insulin. Intestinal growth was markedly elevated in all diabetic groups by 10 days, prior to the increases in hormone levels. We conclude that the enhanced intestinal growth in diabetes is probably independent of growth hormone.

Calcium uptake by brush border membrane vesicles from rat small intestine measured under initial rate conditions comprises both saturable and nonsaturable components. Because the brush border is a lipid bilayer and may be sensitive to changes in membrane lipid, vesicles were treated with liposomes to enrich phospholipid (PL) or cholesterol (C) content above that of the control (Reference) vesicle. The effects of the changes in lipid composition on membrane fluidity were determined from fluorescence anisotropy (r) of diphenylhexatriene. Compared with Reference vesicles, liposome-treated vesicles showed decreased Vmax for saturable and KD for nonsaturable uptakes. Liposome treatment changed vesicle phospholipid composition compared with Reference vesicles. Liposome-treated vesicles had similar phospholipid composition but differed in greater cholesterol content of C- compared with PL-vesicles. Mean Vmax and KD were lower in C- than PL-vesicles, but the difference did not reach statistical significance, although fluidity was significantly lower in C- than PL-vesicles. The mechanism of inhibition of saturable calcium uptake in PL- and C-vesicles was uncompetitive. Thus, lipid composition is crucial for determining calcium uptake: any change from native lipid composition decreased transport. Fluidity, measured by the conventional probe diphenylhexatriene, did not correlate with calcium uptake by Reference compared with liposome-treated vesicles.

Activities of the enzymes lactase, sucrase, maltase, alkaline phosphatase, and superoxide dismutase (SOD) were measured in mucosa of duodenum and ileum of the rat after 70% resection of mid-small intestine or sham operation (transection). We also measured the concentrations of zinc, copper, and manganese in several tissues to assess trace metal homeostasis postresection. Resection resulted in decreased specific activities of disaccharidases and alkaline phosphatase in duodenum, while specific activities remained unchanged in ileum. Specific activity of total SOD (the sum of Cu-Zn and Mn SOD) and Mn SOD was the same in duodenum after resection but was markedly increased in ileum. Tissue trace metal concentrations changed minimally. Because of postresection mucosal growth, total segmental activity of disaccharidases and alkaline phosphatase was the same in duodenum and increased in ileum of resected compared to transected rats. Segmental activity of total SOD and Mn SOD doubled in duodenum and trebled in ileum of resected as compared to transected rats. Thus, total segmental enzyme activity is maintained or increased postresection by increased enterocyte proliferation rate and mucosal growth.

Loss of amino acid into the lumen may be important in diarrheal states. Labeled alpha-aminoisobutyric acid (AIB) was given parenterally, and concentration gradients developed between lumen, intestinal tissue and plasma. After 24 h, we measured AIB loss into the intestinal lumen by recirculating isolated segments in situ under conditions of either net water absorption or net water secretion. Final 14C-AIB concentrations in intestinal tissue were 200-800 times that of lumen, 6--15 times that of serum. Despite increased total 14C-AIB loss during net water secretion, and based on the low luminal 14C-AIB concentrations, the contribution of amino acid loss to fecal nitrogen during osmotic diarrhea appears to be minimal.