Stimulating effect of pentagastrin on cancer cell proliferation kinetics in chemically induced colon cancer in rats

Pharmacological doses of pentagastrin or gastrin are known to stimulate cell proliferation in normal colonic epithelium but the growth-promoting effect of gastrin on colon carcinoma is still controversial. In this study morphological parameters were measured to study the effect of pentagastrin (240 micrograms/kg) on the cell proliferation kinetics in experimental tumours. Colon cancer was produced in rats by weekly injections (20 mg/kg b.wt.) of 1.2-dimethylhydrazine for 24 weeks. Tritiated thymidine was given after administration of pentagastrin or the control solution to the animals. 75% of the animals from the pentagastrin group and 66% of the controls had at least one colon cancer. Autoradiographs of the colonic tumors were performed and the percentage of labeled cells in the cancer cell population was determined after counting 4000 to 16,000 cancer cells per tumor. The labeling index for cancer cells in the pentagastrin-treated group (21.49 +/- 1.76%) was higher (P less than 0.01) than in the control group (14.76 +/- 0.66%). In a second study vincristine sulphate (1 mg/kg) was given to the animals 20 h after administering pentagastrin or the control solution. The percentage of arrested metaphases in the tumours was determined after counting 10,000 to 24,000 cancer cells per histological section. Pentagastrin increased (P less than 0.01) the mean metaphase index by 108% (4.9 +/- 0.44% vs 2.35 +/- 0.32%). These data indicate that cell cycle manipulation of colon cancer is possible with hormonal peptides.     

Ornithine decarboxylase in large bowel mucosa: regulation by gastrin, secretin and EGF.

Rats were fasted 48 h and then injected once with either saline, pentagastrin, EGF, secretin or combinations of secretin and pentagastrin or EGF. Another group of rats was fasted and refed. Animals were killed 4 h later and ODC assayed in mucosa of the cecum, proximal colon, and distal colon. EGF significantly increased ODC activity in all 3 tissues. Secretin had no effect by itself on ODC or ODC stimulated by EGF. Pentagastrin significantly increased ODC of the cecum, and secretin completely inhibited the effect of pentagastrin. Refeeding fasted rats significantly induced activity in all three tissues. Immunocytochemistry using a highly specific polyclonal ODC antibody showed that ODC was confined to the crypt cells of the proximal colon. Antibody dilution techniques demonstrated that gastrin, EGF and refeeding increased the level of enzyme in these cells. Refeeding in addition caused the appearance of enzyme in surface epithelial cells. These results showed that colonic mucosal ODC is present in proliferative cells and is regulated by the same peptides known to regulate growth in this tissue. Colonic mucosal ODC also responds the same way as it does in the oxyntic gland and small bowel mucosa.     

The effects of antagonists of receptors for gastrin, cholecystokinin and bombesin on growth of gastroduodenal mucosa and pancreas.

The effects of gastrin, cholecystokinin (CCK) and bombesin on the DNA synthesis, as a biochemical indicator of trophic action in the gastroduodenal mucosa and the pancreas have been examined in rats fasted for 48 h and in rats refed for 16 h with or without administration of specific receptor antagonists for bombesin, gastrin and CCK. Bombesin and gastrin administered three times daily for 48 h in fasted rats significantly increased the rate of DNA synthesis as measured by the incorporation of [3H] thymidine into DNA in each tissue tested. CCK significantly increased DNA synthesis in the duodenal mucosa and pancreatic tissue, but not in the gastric mucosa. The stimulation of DNA synthesis induced by bombesin in the gastroduodenal mucosa and pancreas was abolished by bombesin/GRP receptor antagonist, RC-3095. RC-3095 did not affect DNA synthesis stimulated by gastrin and CCK in these tissues. L-365,260, a receptor antagonist for gastrin suppressed the DNA synthesis induced by gastrin but not by CCK or bombesin in the gastrointestinal mucosa and pancreas. L-364,718 a specific antagonist for CCK receptors was effective only against CCK stimulated duodenal mucosa and pancreatic growth. Refeeding of 48 h fasting rats strongly enhanced the DNA synthesis in all tissues tested, and this effect was significantly reduced in the gastroduodenal mucosa by blocking only gastrin receptors (with L-365,260) and that in the duodenal mucosa and the pancreas by antagonizing of CCK receptors (with L-364,718). Antagonism of bombesin receptors (with RC-3095) did not significantly affect the stimulation of DNA synthesis induced by refeeding in all tissues tested. This study indicates that the stimulation of DNA synthesis can be achieved by exogenous gastrin, CCK and bombesin acting through separate receptor but that only gastrin and CCK play the major role in the postprandial stimulation of the growth of gastroduodenal mucosa and pancreatic tissue.     

Gastrin and epidermal growth factor induction of ornithine decarboxylase in rat colonic explants

An organ culture system was utilized to examine the effect of gastrin (G-17-I) and epidermal growth factor (EGF) on colonic mucosal ornithine decarboxylase (ODC) activity, and the expression of the ODC gene. Exposure of colonic mucosal explants to either gastrin or EGF (50-500 ng/ml) for only 4 h resulted in a profound stimulation (150-600%) in ODC activity over the basal level. These increases were essentially abolished by difluoromethylornithine (DFMO; 2 nmol/ml) or CaCl2 (2 umol/ml). Gastrin also activated the ODC gene in the colonic mucosa as evidenced by increased steady-state ODC mRNA levels in the colonic mucosal explants after 4 h exposure to the hormone, when compared with the controls. It is concluded that colonic mucosal ODC is responsive to both gastrin and EGF.     

The effect of antagonist of receptors for gastrin, cholecystokinin and bombesin on growth of gastroduodenal mucosa and pancreas.

The effects of gastrin, cholecystokinin (CCK) and bombesin on the DNA synthesis, as a biochemical indicator of trophic action in the gastroduodenal mucosa and the pancreas, have been examined in rats fasted for 48 h and in rats refed for 16 h with or without administration of specific receptor antagonists for bombesin, gastrin and CCK. Bombesin and gastrin administered three times daily for 48 h in fasted rats significantly increased the rate of DNA synthesis as measured by the incorporation of [3H] thymidine into DNA in each tissue tested. CCK significantly increased DNA synthesis in the duodenal mucosa and pancreatic tissue, but not in the gastric mucosa. The stimulation of DNA synthesis induced by bombesin in the gastroduodenal mucosa and pancreas was abolished by bombesin/GRP receptor antagonist, RC-3095. RC-3095 did not affect DNA synthesis stimulated by gastrin and CCK in these tissues. L-365,260, a receptor antagonist for gastrin suppressed the DNA synthesis induced by gastrin but not by CCK or bombesin in the gastrointestinal mucosa and pancreas. L-364,718, a specific antagonist for CCK receptors was effective only against CCK stimulated duodenal mucosa and pancreatic growth. Refeeding of 48 h fasting rats strongly enhanced the DNA synthesis in all tissues tested, and this effect was significantly reduced in the gastroduodenal mucosa by blocking only gastrin receptors (with L-365, 260) and that in the duodenal mucosa and the pancreas by antagonizing of CCK receptors (with L-364,718). Antagonism of bombesin receptors (with RC-3095) did not significantly affect the stimulation of DNA synthesis induced by refeeding in all tissues tested. This study indicates that the stimulation of DNA synthesis can be achieved by exogenous gastrin, CCK and bombesin acting through separate receptors, but that only gastrin and CCK play the major role in the postprandial stimulation of the growth of gastroduodenal mucosa and pancreatic tissue.     

The effects of fasting and refeeding on serum parathormone and calcitonin concentrations in young and old male rats.

Although fasting and refeeding reveal the existence of age-related changes in carbohydrate and lipid metabolism, the effects of aging on mineral metabolism in refed animals are unknown. We therefore investigated hormonal regulation of calcium metabolism in young (4 months) and old (26 months) male rats fasted for 48 hours and then refed for 4 or 24 hours. Serum concentrations of total and ionized calcium and parathormone were similar in control young and old rats. Serum calcitonin level was higher, and the concentrations of albumin and inorganic phosphate and alkaline phosphatase activity were lower in fed old rats. In young fasted rats, the serum ionized and total calcium was decreased, and phosphate concentration was increased. In old rats, fasting resulted in the increase of serum parathormone level. Fasting reduced serum alkaline phosphatase activity to a similar extent in both age groups. In young rats, refeeding for 24h normalized serum calcium and phosphate levels and alkaline phosphatase activity, and decreased serum concentrations of PTH and calcitonin. In old refed rats, serum calcitonin concentration was raised by 77% compared to fed or fasted animals, whereas parathormone levels were normalized. Our results indicate that old fasted or refed rats maintain normal serum calcium concentration in a different way than young animals, possibly through the increase in serum levels of parathormone and/or calcitonin. Thus, dietary manipulations such as fasting and refeeding constitute an interesting model for the investigation of the effects of aging on the hormonal regulation of serum calcium level.     

Evaluation of the effects of pentagastrin, gastrin and pancreatic glucagon on cell proliferation in the rat gastrointestinal tract

The effects of six injections of a range of doses (100-1000 micrograms/kg bodyweight) of pentagrastrin and single injection of a range of doses of porcine gastrin (10-40 micrograms/kg bodyweight) and pancreatic glucagon (25-100 micrograms/kg bodyweight) on cell proliferation in the intestine of fasted rats has been investigated. The end-point employed included the measurement of 14C leucine incorporation and thymidine-derived tritium content of the body of the stomach, duodenum, jejunum, ileum and colon. The carbon 14 and tritium content per microgram of tissue in triplicate samples of fifty individually dissected crypts of glands were determined. From these data and the wet weight of the washed, blotted, intestinal segments, values for crypts/micrograms tissue and crypts/segment were calculated. The results demonstrated that pentagastrin at physiological doses decreased cell proliferation slightly in stomach, while gastrin and glucagon were without effect. In the small intestine, pentagastrin and gastrin were without significant effect with the exception that they increased the weight of the duodenum. In contrast, a high physiological dose of glucagon increased DNA and protein synthesis throughout the small bowel, but particularly in the ileum. Pharmacological doses of pentagastrin and all doses of gastrin appeared to increase cell proliferation in the colon although the possibility could not be excluded that this was due to stimulation of precursor uptake. Gastrin also increased colonic weight. Glucagon had no effects in the colon. These observations are compatible with the hypothesis that (i) the primary effects of gastrin and pentagastrin on the proximal intestine are as secretogogues and effects on cell proliferation may be secondary, (ii) gastrin and pentagastrin at physiological levels do not stimulate small intestinal cell proliferation, however glucagon does, and (iii) gastrin at physiological levels and pentagastrin at pharmacological levels may stimulate cell proliferation in the colon.     

Possible involvement of protein kinase C in mediating gastrin-induced response in rat colonic epithelium.

We examined the potential role of protein kinase C in signal transduction induced by gastrin's stimulation of rat colonic epithelium. Protein synthesis ([35S]methionine incorporation into protein) and enzyme activity (decrease in the cytosolic activity) were measured following epithelial stimulation with gastrin. Gastrin (10 nM) increased [35S]methionine incorporation into protein to 265% above maintenance level. The effect of gastrin was comparable to the stimulation induced by phorbol 12-myristate, 13-acetate (PMA), a strong activator of protein kinase C. The increase in protein synthesis induced by gastrin was totally abolished by 1-(5-isoquinolinyl)-2-methylpiperazine, an inhibitor of protein kinase C activity. Gastrin also decreased the cytosolic activity of the enzyme, an index of its activation and subsequent translocation to other cellular compartments. Therefore, we conclude that gastrin may be acting through a protein kinase C mechanism.     

Variations of plasma immunoreactive motilin, pancreatic polypeptide, gastrin and somatostatin along the duodenal motility cycle in the pig

The peripheral plasma concentrations of immunoreactive motilin, pancreatic polypeptide (PP), somatostatin and gastrin were measured in 7 pigs fasted to 24 h and subsequently fed a standard meal. Plasma motilin peaked during the last part of phase II activity of the migrating myoelectric complex (MMC) sequence (25.2 +/- 2.3 pM), the lowest value being recorded during phase I (10.6 +/- 1.5 pM) after a 24 h fast. Plasma motilin remained at a low level during the digestive pattern of duodenal activity, no fluctuation occurring when the first postprandial MMC recurred. At variance analysis, gastrin and PP were not released phasically with MMC in the fasting state, while at autocovariance both peptides tended to fluctuate during the MMC sequence with positive and negative peaks at regular intervals along MMC cycles. No variation of plasma somatostatin was observed in the fasting animals. These findings argue against a major role of circulating PP, gastrin and somatostatin-like components in the control of fasted and post absorptive duodenal motility in pigs while the role of motilin remains equivocal.     

Glycine-extended gastrin exerts growth-promoting effects on human colon cancer cells.

BACKGROUND: Since human colon cancers often contain significant quantities of progastrin-processing intermediates, we sought to explore the possibility that the biosynthetic precursor of fully processed amidated gastrin, glycine-extended gastrin, may exert trophic effects on human colonic cancer cells. MATERIALS AND METHODS: Binding of radiolabeled glycine-extended and amidated gastrins was assessed on five human cancer cell lines: LoVo, HT 29, HCT 116, Colo 320DM, and T 84. Trophic actions of the peptides were assessed by increases in [3H]thymidine incorporation and cell number. Gastrin expression was determined by northern blot and radioimmunoassay. RESULTS: Amidated gastrin did not bind to or stimulate the growth of any of the five cell lines. In contrast, saturable binding of radiolabeled glycine-extended gastrin was seen on LoVo and HT 29 cells that was not inhibited by amidated gastrin (10(-6) M) nor by a gastrin/CCKB receptor antagonist (PD 134308). Glycine-extended gastrin induced a dose-dependent increase in [3H]thymidine uptake in LoVo (143 +/- 8% versus control at 10(-10) M) and HT 29 (151 +/- 11% versus control at 10(-10) M) cells that was not inhibited by PD 134308 or by a mitogen-activated protein (MAP) or ERK kinase (MEK) inhibitor (PD 98509). Glycine-extended gastrin did stimulate jun-kinase activity in LoVo and HT 29 cells. The two cell lines expressed the gastrin gene at low levels and secreted small amounts of amidated gastrin and glycine-extended gastrin into the media. CONCLUSIONS: Glycine-extended gastrin receptors are present on human colon cancer cells that mediate glycine-extended gastrin's trophic effects via a MEK-independent mechanism. This suggests that glycine-extended gastrin and its novel receptors may play a role in colon cancer cell growth.     

Metabolic control of phosphorylase conversion in muscle. Effect of fasting and refeeding on the response of rat diaphragm glycogen phosphorylase, cyclic AMP Dependent protein kinase, and phosphorylase b kinase to adrenergic stimulation.

The influence of fasting and refeeding on the response to adrenergic stimulation of several enzymes involved in glycogen metabolism has been investigated in the isolated, intact rat diaphragm. The in vitro response of the phosphorylase system to terbutaline was found to decrease markedly following fasting. A pronounced increase in this response was seen upon refeeding. This increased responsiveness was normalized by incubation of isolated tissues with palmitate (1.5 mM). Plasma free fatty acid concentration was increased in fasted rats compared to the value found in refed animals. The effect of terbutaline on cyclic AMP concentration and protein kinase activity was not significantly influenced by fasting and refeeding while fasting decreased the effect of terbutaline upon phosphorylase b kinase. Diaphragm glycogen levels were reduced by more than 50% in rats fasted for 24 hours and were significantly increased upon refeeding compared to fed rats. The results indicate that the nutritional state can modulate the sensitivity of the interconverting system for phosphorylase. It is suggested that this modulation might depend upon fatty acid metabolism.     

草鱼在摄食高能饲料后血清生化指标的动态变化

为研究草鱼(Ctenopharyngodon idella) 在摄食高能饲料后血清生化指标的动态变化, 选择均重为(55.0±2.5) g 的健康草鱼320 尾, 随机分成4 组, 每组4个重复, 分别以3组高能纯化饲料(分别以额外的蛋白质、脂肪、糊精供能, 高能饲料组较对照组总能量提高11%)及对照组饲料喂养草鱼11周后, 将鱼体禁食48h后采样(对照), 再饱食投喂, 在摄食后的2h、8h和24h取样, 测定实验鱼8种血清生化指标, 并对采样时间点(T)和不同饲料(D)进行双因素方差分析。为确保实验结果的准确性, 需要保证不同处理组的采样时间同步性, 即均在餐后同一时间点采样。结果显示: 除血清总胆固醇(TCHO)含量外, 血清碱性磷酸酶(ALP)、谷草转氨酶(AST)、谷丙转氨酶(ALT)活性, 以及血清甘油三酯(TAG)、葡萄糖(GLU)、低密度脂蛋白胆固醇(LDLC)、高密度脂蛋白胆固醇(HDLC)含量均受到采样时间点(T)即餐后时间的显著影响, 饲料(D)对上述8个指标亦均有显著影响, 且两者存在交互作用。草鱼血清GLU含量和血清AST活性均在餐后2h达到峰值, 血清ALT和ALP活性以及LDLC含量均在餐后24h达到峰值, 血清TAG含量在餐后8h达到峰值, 而血清TCHO和HDLC含量则无明显峰值。在餐后24h, 3个高能组的ALT活性和GLU含量较对照组显著升高, 血清AST和ALP活性以及TAG、TCHO和HDLC含量较对照组无显著差异。上述结果表明, 草鱼血清生化指标受到餐后采样时间点和饲料的显著影响。     

Gastrin''s trophic effect in the colon: Identification of a signaling pathway mediated by protein kinase C

In previous studies we have reported that gastrin exerts a trophic effect on rat colonic epithelial cells in vitro. The effect of gastrin appeared to be mediated through a protein kinase C mechanism. In this study, we have characterized the role of protein kinase C in the gastrin-induced stimulation. Gastrin, in a time- and dose-dependent manner, increased protein kinase C translocation from the cytosol to the membrane, an index of enzyme activation. Maximum translocation occurred in 1 to 2 min following exposure to gastrin (10⁻⁸ M), before declining back to baseline level within 5 min. Gastrin did not change total protein kinase C activity in the colonic cells. Staurosporine, an inhibitor of protein kinase C, totally abolished the basal as well as the gastrin-stimulated activity of protein kinase C. The tumor promoter phorbol 12-myristate 13-acetate also stimulated colonic epithelial protein kinase C. However, prolonged treatment of cells with phorbol inhibited their subsequent response to gastrin stimulation. The response to gastrin was also prevented by the gastrin receptor antagonist proglumide. These observations suggest that protein kinase C mediates the stimulatory effect of gastrin on colonic epithelial cells, possibly through a receptor mechanism.     

Influence of Hydrocortisone on Chick Embryo Retina Development

Treatment of chick embryos in ovo with hydrocortisone-21-phosphate (a single dose of 150 micrograms) caused a marked reduction of retinal thymidine kinase activity 24 h later. The inhibitory effect was highest (65-70%) in 8-10-day-old embryos and declined with age, disappearing after day 15. It was accompanied by a reduction in thickness of the retinal layers. Adrenocorticotropic hormone (ACTH) treatment (10 micrograms daily for 2 days) also produced an age-dependent inhibitory effect on retinal thymidine kinase, whereas treatment with a single dose of 200 micrograms of metopirone, a compound that prevents the 11 beta-hydroxylation of steroid molecules in the adrenal glands, impeded the decrease in thymidine kinase activity that normally occurs in chick embryo retina after day 9 of development. In addition, metopirone prevented the inhibition exerted by ACTH on thymidine kinase activity but had no effect on the action of hydrocortisone.     

Temporal relationships in the effects of protein-free diet on the activities of rat liver branched-chain ketoacid dehydrogenase complex and kinase

Feeding rats 0% casein diet decreased liver activities of branched-chain ketoacid dehydrogenase complex (active form) and of activator protein (complete within 4 days), and increased activity of branched-chain ketoacid dehydrogenase kinase (complete within 9-10 days). Refeeding normal diet to rats fed 0% casein diet for 10 days resulted in a rapid and partial (approx. 50%) reversal of the above effects within 24 h; complete reversal required 20-30 days of refeeding.     

Evaluation of the Effects of Pentagastrin, Gastrin and Pancreatic Glucagon On Cell Proliferation In the Rat Gastrointestinal Tract

ABSTRACT The effects of six injections of a range of doses (100–1000 μg/kg bodyweight) of pentagrastrin and single injection of a range of doses of porcine gastrin (10–40 μg/kg bodyweight) and pancreatic glucagon (25–100 μg/kg bodyweight) on cell proliferation in the intestine of fasted rats has been investigated. the end-point employed included the measurement of ¹⁴C leucine incorporation and thymidine-derived tritium content of the body of the stomach, duodenum, jejunum, ileum and colon. the carbon 14 and tritium content per μg of tissue in triplicate samples of fifty individually dissected crypts of glands were determined. From these data and the wet weight of the washed, blotted, intestinal segments, values for crypts/μg tissue and crypts/segment were calculated. the results demonstrated that pentagastrin at physiological doses decreased cell proliferation slightly in stomach, while gastrin and glucagon were without effect. In the small intestine, pentagastrin and gastrin were without significant effect with the exception that they increased the weight of the duodenum. In contrast, a high physiological dose of glucagon increased DNA and protein synthesis throughout the small bowel, but particularly in the ileum. Pharmacological doses of pentagastrin and all doses of gastrin appeared to increase cell proliferation in the colon although the possibility could not be excluded that this was due to stimulation of precursor uptake. Gastrin also increased colonic weight. Glucagon had no effects in the colon. These observations are compatible with the hypothesis that (i) the primary effects of gastrin and pentagastrin on the proximal intestine are as secretogogues and effects on cell proliferation may be secondary, (ii) gastrin and pentagastrin at physiological levels do not stimulate small intestinal cell proliferation, however glucagon does, and (iii) gastrin at physiological levels and pentagastrin at pharmacological levels may stimulate cell proliferation in the colon.     

The effect of total parenteral nutrition (TPN) on gastrin release in the rat

The effect of short-term (7 days) total parenteral nutrition (TPN) on gastrin release was studied in vivo and in the isolated vascularly perfused rat stomach. The daily plasma gastrin concentration of parenterally fed rats was significantly lower than in ad lib fed control animals (53 +/- 17 pg/ml vs 159 +/- 32 pg/ml, P less than 0.05) as early as day 2 and a similar pattern was observed on days 4 and 6. The fasting plasma gastrin concentration of control animals was 2-fold greater than of the parenterally fed group (P less than 0.05). Following oral peptone, the gastrin response of TPN and control animals doubled although peak gastrin levels were greatly reduced in TPN rats. Basal gastrin release from the perfused stomachs of control rats was 2-fold greater than from TPN rats (P less than 0.05). Electrical stimulation of the vagal trunks resulted in a significantly greater elevation in gastrin secretion from control stomachs compared to TPN animals (4-fold vs. 2.4-fold increase, P less than 0.05). Quantification of the antral G-cell population revealed a significant reduction in the number of G-cell of TPN rats compared to controls (97 +/- 8 cells/mm vs 76 +/- 6 cells/mm, P less than 0.05). These results indicate that luminal nutrient stimulation is necessary for the maintenance of normal G-cell secretory activity in vivo and from the in vitro stomach. G-cell hypoplasia appears to be partially responsible for reduced gastrin output to basal and stimulated conditions after TPN.     

Gastrin and the ultrastructure of G cells after stimulation with acetylcholine

The effect of intragastric administration of acetylcholine on serum and antral gastrin concentrations of rats has been examined using a radioimmunoassay and quantitative electron microscopy. Exposure of the stomach of rats, previously fasted for 24h, to 2% acetylcholine for either 0.5 or 2h resulted in a significant 4--5 fold increase in serum gastrin concentrations to levels similar to those found in fed animals. Such treatment produced no detectable change in antral gastrin concentration or in the number or electron density of secretory granules in the G cells. This lack of detectable change in the G cells was not unexpected since our calculations suggest that less than 10% of the total gastrin stored in the antrum is released over 2h as a result of the stimulation with acetylcholine. The proportion of electron-lucent secretory granules was, however, markedly increased by prolonged fixation in aldehydes. The increase was similar in both ACh stimulated and control animals. These results indicate that the ultrastructural appearance of G cell secretory granules in influenced far more by the conditions of fixation than by the release of gastrin. They therefore cast considerable doubt on the hypothesis that gastrin is released by molecular dispersion from the granules.     

Somatostatin content and binding in small intestinal mucosa from fed, fasted, and refed rabbits

The present study is an investigation of the effects of 12- to 96-hours' starvation and 96-hours' starvation plus 48-hours' refeeding on both somatostatin-like immunoreactivity (SLI) and cytosolic somatostatin binding sites in rabbit small intestinal mucosa. The SLI concentration increased after 24 h in duodenal and jejunal mucosa, but not in ileal mucosa, and reached its highest value after 96 h of fasting. The number of specific high and low-affinity somatostatin binding sites, but not their affinity, decreased with the duration of fasting in the same gut segments, refeeding of fasted animals resulted in a return to normal control values for small intestine mucosal SLI and somatostatin binding.