gastrins and Starvation

Topics: Animals; Female; Gastric Juice; Gastrins; Gonadal Steroid Hormones; Male; Pituitary Hormones, Anterior; Prolactin; Sex Factors; Starvation

The lining of the intestinal tract is constantly renewed in a brisk but orderly fashion. Further acceleration of cell renewal is elicited by various stimuli, notably surgical shortening of the intestine and hyperphagia, which lead to prompt but persistent increases in mucosal mass. Progressive hypoplasia ensues when the small and large bowel are deprived of their normal contents, either by fasting (with or without parenteral nutrition) or by exclusion from intestinal continuity. All atrophic changes are reversed by refeeding or restoration of the normal anatomical disposition. Intestine responds to mucosal damage by regeneration from the crypts. Pancreatobiliary secretions mediate some of the tropic effects of chyme; systemic influences, both neurovascular and humoral, also play a part in the adaptive response of the gut.

Topics: Adaptation, Physiological; Adult; Animals; Cell Division; Colectomy; Colostomy; Female; Gastrins; Glucagon-Like Peptides; Humans; Hyperphagia; Hyperplasia; Hypertrophy; Ileum; Intestinal Diseases; Intestinal Mucosa; Intestines; Jejunum; Obesity; Parenteral Nutrition; Rats; Starvation

Topics: Animals; Cholecystokinin; Dactinomycin; DNA; Gastrectomy; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Growth Hormone; Intestinal Mucosa; Intestine, Small; Liver; Pancreas; Pentagastrin; Protein Biosynthesis; Secretin; Starvation; Vasoactive Intestinal Peptide

There is evidence that under various physiological circumstances long-term adaptation of structure and function of the gut occurs. The mechanisms of these changes are not clear but gastro-intestinal hormones may be involved. In particular, gastrin which has been shown experimentally to stimulate growth and development of parts of the gut, probably has a role in maintaining the structure of the normal upper alimentary tract. Cholecystokinin may be of major importance in producing adaptive changes in the pancreas in response to dietary modifications and enteroglucagon is possibly concerned with maintaining a normal small intestinal structure. The importance of the 'trophic' action of gatrointestinal hormones is becoming more widely recognised and as new gastro-intestinal hormones become established, this aspect of their physiological importance as well as their acute effects, will deserve attention.

Topics: Animals; Cholecystokinin; DNA; Duodenum; Female; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Humans; Intestinal Diseases; Intestine, Small; Kidney Failure, Chronic; Lactation; Pancreas; Pregnancy; Rats; Secretin; Starvation; Weaning; Zollinger-Ellison Syndrome

Refeeding starved rats with a fibre free 'elemental' diet increased crypt cell production rate (CCPR) in the proximal small intestine but not in the distal regions of the gut. Little effect on CCPR was seen when inert bulk (kaolin) was added to the 'elemental' diet. Addition of a poorly fermentable dietary 'fibre' (purified wood cellulose) had little effect on intestinal epithelial cell proliferation except in the distal colon where it significantly increased CCPR. A more readily fermentable 'fibre' (purified wheat bran) caused a large proliferative response in the proximal, mid and distal colon and in the distal small intestine. A gel forming 'fibre' also stimulated proliferation in the distal colon. There was no significant correlation between CCPR and plasma gastrin concentrations, but plasma enteroglucagon concentrations were significantly correlated with CCPR in almost all the sites studied. Plasma PYY concentrations also showed some correlation with CCPR, especially in the colon. Thus, whilst inert bulk cannot stimulate colonic epithelial cell proliferation, fermentable 'fibre' is capable of stimulating proliferation in the colon, and especially in the distal colon: it can also stimulate proliferation in the distal small intestine and it is likely that plasma enteroglucagon may have a role to play in this process.

Topics: Animals; Cell Division; Colon; Dietary Fiber; Epithelial Cells; Food, Formulated; Gastrins; Gastrointestinal Hormones; Glucagon-Like Peptides; Intestine, Small; Male; Peptide YY; Peptides; Rats; Rats, Inbred Strains; Starvation

It has been shown that the ghrelin receptor, GH secretagogue receptor (GHS-R), is synthesized in neurons of the nodose ganglion and then transmitted to axon terminals, where it binds to ghrelin. The orexigenic signal of ghrelin secreted from the stomach is transmitted to the brain via the vagal afferent nerve. To explore the regulation of GHS-R synthesis in the nodose ganglion, we examined whether or not GHS-R type a mRNA expression shows circadian rhythm, and is affected by starvation, vagotomy, or i.v. administration of gastrointestinal peptides. Nodose ganglion GHS-R mRNA levels showed a diurnal rhythm, being high during periods of light and low during darkness. Although starvation tended to increase the level of GHS-R mRNA, a more significant increase was observed upon re-feeding. Vagotomy decreased the level of GHS-R mRNA significantly in comparison with animals that underwent a sham procedure. Cholecystokinin and gastrin increased the level of GHS-R mRNA after 2 h, but after 4 h, the level decreased. These results suggest that GHS-R synthesis in the nodose ganglion is regulated centrally and peripherally by neuronal and humoral information, and that these dynamic changes of GHS-R mRNA expression may be involved in the regulation of feeding by ghrelin.

Topics: Animals; Cholecystokinin; Circadian Rhythm; Gastrins; Gene Expression Regulation; Male; Nodose Ganglion; Rats; Rats, Wistar; Receptors, G-Protein-Coupled; Receptors, Ghrelin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Starvation; Vagotomy

Gastrointestinal hormones control gut functions in response to enteral nutrition. Diseases involving the gastrointestinal tract, such as necrotizing enterocolitis, may affect gut hormone secretion and therefore influence gut functions. Because bowel rest is an important part of the treatment, infants with this disease are especially at risk for an altered gut hormone secretion and thus for compromised gut functions.. In the current study, the gastrointestinal hormone profiles of eight preterm infants with an ileostomy after necrotizing enterocolitis (Bell stages 2 and 3) were evaluated during starvation and reintroduction of enteral nutrition. Basal and postprandial plasma concentrations of gastrin, cholecystokinin, and peptide YY were measured with sensitive and specific radioimmunoassays. The results were compared with those of 11 controls.. In the patients and the controls, plasma concentrations of all hormones were higher postprandially. The increases in cholecystokinin and peptide YY were significant in the patients. Compared with the controls, all concentrations were higher in the patients, and changes were significant for basal and postprandial cholecystokinin and postprandial peptide YY.. Enteral nutrition stimulates the secretion of gastrointestinal hormones, also in premature infants with a diseased distal small bowel and colon, as in necrotizing enterocolitis. The postprandial increase of peptide YY in patients with an ileostomy indicates that enteral substrate in the colon is not necessary for stimulation of peptide YY secretion.

Topics: Cholecystokinin; Enteral Nutrition; Enterocolitis, Necrotizing; Gastrins; Gastrointestinal Hormones; Humans; Ileostomy; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Peptide YY; Postprandial Period; Radioimmunoassay; Starvation

The turnover of the epithelium of the gastrointestinal tract is regulated by a balance between cell multiplication and cell loss. We examined the effects of starvation on apoptosis in endocrine and other epithelial cells of rat antropyloric mucosa. Apoptosis was determined by the TUNEL reaction combined with immunocytochemical staining for gastrin and somatostatin. Apoptotic cell morphology was determined by bisbenzimide staining for DNA. Both gastrin and somatostatin cells showed a significantly lower apoptotic index than the general epithelium. This agrees with the longer turnover kinetics of gastric endocrine cells. On starvation, the apoptotic index of the general epithelium and of the gastrin but not of the somatostatin, cells increased significantly. This was prevented by the nitric oxide synthase (NOS) inhibitor L-NAME but not by its inactive stereoisomer D-NAME. Immunoreactive neuronal NOS was present in somatostatin cells, in nonendocrine cells predominating in the surface and pit epithelium, and in rare nerve fibers. Endothelial cell NOS was present in vessels, whereas the inducible isoform was barely detectable. Thus, endogenous NOS isoforms participate in regulating antropyloric epithelial apoptosis during starvation. The close paracrine relation between somatostatin cells and gastrin cells suggests that the former regulates apoptosis of the latter through release of NO.

Topics: Animals; Apoptosis; Eating; Female; Gastric Mucosa; Gastrins; Immunohistochemistry; In Situ Nick-End Labeling; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Pyloric Antrum; Rats; Rats, Wistar; Somatostatin; Starvation

Chemically biotin-labeled oligonucleotides form attractive reagents, as large quantities of stable and well-defined probes can easily be produced. Their usefulness for in situ hybridization was tested using rat gastrin cells as a model. Two probes recognizing two different regions of rat gastrin mRNA were synthesized and produced specific and equally strong hybridization signals. A probe complementary to human gastrin mRNA, but with mismatches to the rat gastrin mRNA sequence, failed to reveal rat gastrin cells under the stringency conditions used. Northern blotting revealed that the rat gastrin mRNA probes reacted exclusively with the appropriately sized (approximately 650 bases) mRNA. Model systems demonstrated that the hybridization signal, as revealed by alkaline phosphatase-based detection, varied linearly with the 10logarithm of target concentration and also showed that a new detection system was much more sensitive than previously used systems. In agreement with previous biochemical data, image analysis showed that starvation of rats led to a progressive decrease in cell staining intensities and cell numbers. Double staining for rat gastrin mRNA and gastrin immunoreactivity showed that in adult rats almost all gastrin cells expressed both mRNA and protein. Similar studies on developing rat gastrin cells revealed discrepancies between gastrin mRNA and gastrin-immunoreactive cells during the first week of newborn life. Subsequently, expression of mRNA and protein in the cells became gradually more concordant.

Topics: Animals; Animals, Newborn; Base Sequence; Gastric Mucosa; Gastrins; Immunoenzyme Techniques; In Situ Hybridization; Male; Microscopy, Fluorescence; Molecular Sequence Data; Oligonucleotide Probes; Rats; Rats, Wistar; RNA, Messenger; Sensitivity and Specificity; Starvation

Antral gastrin and somatostatin gene expression during starvation and after refeeding with liquid meals of varying composition were studied. Northern and slot-blot hybridization analyses showed that starvation caused a marked decrease in antral gastrin messenger RNA (mRNA) level by 12 hours associated with an increase in somatostatin mRNA. After 48 hours of fasting, antral gastrin mRNA was 26% and somatostatin mRNA was 136% of their prefasting levels. Refeeding caused increased 2-hour integrated gastrin mRNA levels after liquid peptone (+45%), phenylalanine (+31%), and olive oil (+13%), but no changes were observed with glucose or saline solutions. Integrated 2-hour immunoreactive antral gastrin content was increased after peptone (+106%), phenylalanine (+68%), and olive oil (+32%) meals but was not increased after glucose (-11%) or saline (-10%). In some cases, both gastrin mRNA and peptide responses could be measured as early as 15 minutes. The same nutrients that increased gastrin mRNA levels caused decreased 2-hour integrated somatostatin mRNA levels; peptone (-30%), phenylalanine (-28%), and olive oil (-21%), but neither glucose nor saline, altered somatostatin mRNA levels. These results suggest that antral gastrin and somatostatin genes were regulated in opposite directions, in a coordinate manner, by specific gastric nutrients that stimulate gastrin release.

Topics: Animals; Food; Gastrins; Gene Expression Regulation; Male; Peptides; Pyloric Antrum; Rats; Rats, Inbred Strains; RNA, Messenger; Somatostatin; Starvation

We have examined the regulation of gene expression and post-translational processing of progastrin by starvation and feeding in rats. An oligonucleotide complementary to rat preprogastrin cDNA was used in RNA blot and hybridization analysis to measure gastrin mRNA levels. A region-specific antibody raised against the predicted amino acid sequence of the carboxyl terminal extension of progastrin was used for quantitation of progastrin peptides. The effects of starvation and of refeeding on rat antral gastrin mRNA and pro-hormone peptide levels were examined in rats starved for 48 h and after refeeding with a solid meal. Antral gastrin mRNA concentrations decreased to a plateau level (30% of the nonstarved control) after 48 h of starvation. Immunoreactive gastrin concentration decreased threefold, but progastrin processing intermediates did not decrease significantly during fasting. Following refeeding, significant increases in antral mRNA level were detected in 1 h, and peak levels were reached by 2 h (more than two times higher than starved control). There was a rapid and significant decrease in progastrin immunoreactivity within 30 min, followed by a significant increase in gastrin immunoreactivity 2 h after refeeding. These data suggest that rapid increases of blood and tissue gastrin levels in response to food may be associated with increases in both gastrin gene expression and post-translational processing of progastrin.

Topics: Animals; Gastrins; Gene Expression Regulation; Immunoassay; Male; Osmolar Concentration; Protein Processing, Post-Translational; Pyloric Antrum; Rats; Rats, Inbred Strains; RNA, Messenger; Somatostatin; Starvation

Serum gastrin concentration and antral gastrin content were measured in 4-5- and 26-28-mo rats under fed conditions, after 3 days of starvation, and after 1 day of refeeding after starvation, to determine whether gastrin homeostasis is altered during aging. Gastric weight was 29% greater, but antral weight and DNA were less in the older rats. Serum gastrin fell during starvation and rose during refeeding in both groups, but it was lower in aging rats only during refeeding. Antral gastrin content in older animals was 60% of that in young rats. Starvation reduced antral gastrin only in the young, whereas refeeding lowered antral gastrin in the older animals. We conclude that, in aging rats, the relationship of serum and antral gastrin is altered during changes in food intake.

Topics: Aging; Animals; DNA; Food; Gastric Mucosa; Gastrins; Homeostasis; Male; Organ Size; Pyloric Antrum; Rats; Rats, Inbred F344; Starvation

The influence of food deprivation on gastric G- and D-cells and on parietal cells was studied in the rat. In fed controls and groups of rats fasted for 12 and 96 h G-, D- and parietal cell densities, somatostatin and gastrin concentration in antral and fundic specimens and serum gastrin were compared. Gastrin in antral mucosa, serum gastrin, G-cell density as well as antral D-cell density decreased in long-term fasted rats by 52%, 90%, 58% and 42%, respectively. Fundic D-cell density remained unchanged. After 96 h starvation somatostatin concentration slightly increased in antral mucosa (+35%; P less than 0.05), but decreased in fundic mucosa (-40%; P less than 0.05). Parietal cell density was not influenced by prolonged fasting. These findings demonstrate that changes in D-cell morphology and mucosal somatostatin content are not parallel and that the rat gastric D-cell is less dependent on food in the gastric lumen than the G-cell. The unaltered fundic D-cell density reflects the functional activity of gastric D-cell which has also been shown to be independent of the presence or absence of food.

Topics: Animals; Body Weight; Gastric Fundus; Gastric Mucosa; Gastrins; Male; Organ Size; Pyloric Antrum; Rats; Rats, Inbred Strains; Somatostatin; Starvation

The gastrin cells (G cells) in the rat pyloric antrum after 7, 14, 21 and 28 days of starvation were investigated by immunohistochemistry and electron microscopy. In the peroxidase anti-peroxidase method for light microscopy, gastrin immunoreactive cells during starvation markedly decreased in number and size. Quantitative electron microscopy revealed that during starvation the number of electron-lucent granules were greatly reduced, but the number of electron-dense granules increased; the number of intermediate granules were not remarkably changed in G cells. These results may suggest that the synthesis of gastrin and granule maturation were greatly inhibited during long-term starvation.

Topics: Animals; Gastrins; Histocytochemistry; Immunochemistry; Male; Microscopy, Electron; Pyloric Antrum; Rats; Rats, Inbred Strains; Starvation

The effects of starvation and refeeding on intestinal cell proliferation at several sites of the rat gastrointestinal tract were studied and used as a model of altered cell proliferation in order to investigate the relationship between the rate of cell production and plasma gastrin and enteroglucagon. There was a marked fall in crypt cell production rate after four days starvation, with the proximal sites of the gut being most affected. The response to refeeding varied with site, suggesting that there was more than one mechanism for the control of intestinal cell proliferation. Plasma gastrin and enteroglucagon both fell to one fifth of their control level after starvation. Plasma gastrin increased slowly after refeeding, whilst plasma enteroglucagon increased rapidly to values significantly above control. Plasma gastrin was only correlated with crypt cell production in the duodenum, while plasma enteroglucagon was correlated with crypt cell production rate at several sites, indicating that enteroglucagon may be involved in the control of intestinal cell production.

Topics: Animals; Cell Count; Cell Division; Duodenum; Gastrins; Gastrointestinal Hormones; Glucagon-Like Peptides; Intestinal Mucosa; Male; Metaphase; Rats; Rats, Inbred Strains; Starvation; Time Factors

The effects of starvation on the tissue concentrations of some peptides common to the gastrointestinal tract and the central nervous system have been examined. Groups of 6 rats were either fed ad libitum or starved for up to 4 days and killed by decapitation. Antrum, fundus, duodenum, jejunum, ileum, colon, pancreas and brain were dissected, weighed and then frozen on dry ice. The tissues were extracted sequentially in boiling water and 3% acetic acid, centrifuged and the supernatants radioimmunoassayed for gastrin, cholecystokinin (CCK), vasoactive intestinal peptide (VIP), gastric inhibitory peptide (GIP) and somatostatin. Each peptide was not assayed in each tissue. Starvation had no effect on the concentrations of peptides measured in the fundus (somatostatin and VIP), ileum (somatostatin, GIP, VIP) and colon (somatostatin, GIP, VIP). VIP concentration was increased in the jejunum and GIP was increased in both the duodenum and jejunum. Antral gastrin was the only peptide in the gastrointestinal tract to be decreased by food deprivation. Somatostatin concentration was approximately doubled in the antrum, duodenum, jejunum and pancreas. Brain VIP was unchanged. Brain somatostatin and CCK were significantly reduced by starvation. We conclude that starvation results in organ-specific and hormone-specific alterations in tissue concentrations of peptides of the gastrointestinal tract and the central nervous system.

Topics: Animals; Brain; Cholecystokinin; Digestive System; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Male; Rats; Somatostatin; Starvation; Vasoactive Intestinal Peptide

Because exogenous gastrin has been implicated as a tropic hormone for mucosal cells of the intestinal tract and as a regulator of mucosal growth, we studied the effects on the gut of endogenous 23-fold variations of serum gastrin produced by various gastric operations. These were pyloroplasty, vagotomy and pyloroplasty, antrectomy, and fundectomy. After jejunal resection, RNA content, DNA content, incorporation of [3H]thymidine into DNA, crypt depth, and villus height in midgut and ileum were independent of gastrin levels. Loss of RNA and DNA during starvation was not prevented by high endogenous concentrations of serum gastrin, and DNA specific activity was not affected. Tropic effects distal to the duodenum produced by exogenous gastrin and pentagastrin may be results of supranormal levels.

Topics: Animals; DNA; Gastrins; Jejunum; Male; Pyloric Antrum; Pylorus; Rats; RNA; Starvation; Stomach; Time Factors; Vagotomy

Intestinal DNA, RNA, and protein content were decreased to a greater extent than was body weight when rats were starved for 3 days. Specific lactase and maltase activity increased with progressively longer periods of starvation. Antral and serum gastrin concentration significantly decreased during the 3 days of starvation. Pentagastrin (250 mug/kg 3 times daily) was injected into a group of rats for the duration of a 3-day starvation period and caused a small but significant increase in the relative intestinal RNA and protein content and decreased lactase and maltase specific activities in comparison with the levels of 3-day starved controls. Pentagastrin thus partially reversed some of the starvation-induced changes toward fed levels. Thus, a deficiency in the trophic hormone gastrin may be partially responsible for the disproportionate changes in intestinal tissue during starvation.

Topics: Animals; Disaccharides; DNA; Galactosidases; Gastrins; Glucosidases; Histocytochemistry; Humans; Intestine, Small; Male; Pentagastrin; Proteins; Radioimmunoassay; Rats; RNA; Starvation

Plasma lipid and hormone levels have been measured during 72 hours total starvation in nine healthy subjects, to assess the relative importance of hormones and substrates in human triglyceride metabolism. Plasma free fatty acid and glycerol concentrations rose steadily on each day of starvation. Plasma triglyceride concentrations rose on the second and third days, from a control level of 649 +/- 67 mg/1 to a maximum of 1001 +/- 66 mg/1. Plasma cholesterol concentrations remained unchanged while glucose concentrations fell and insulin did not change. Plasma glucagon (C-GLI) levels doubled while secretin levels, reported previously, rose threefold. It is suggested that during acute starvation the rise in triglyceride concentration results from the increased availability of free fatty acids, and that elevated secretin and glucagon levels enhance lipolysis and hence provide substrates for triglyceride synthesis.

Topics: Adult; Cholesterol; Fatty Acids, Nonesterified; Female; Gastrins; Glucagon; Glycerol; Humans; Insulin; Male; Secretin; Starvation; Time Factors; Triglycerides

In rats fasted 4 days, immunoreactive gastrin concentrations decreased to one-third of the fed levels in antral tissue and to one-eight of the fed levels in serum. The number of antral cells that reacted with fluorescent antigastrin antiserum was also correspondingly decreased. After refeeding, serum gastrin returned to normal levels in 6 days, whereas antral gastrin concentration recovered after 9 days. Normal gastrin levels were maintained in rats fed a nutritious liquid diet over a 6-day period, whereas tissue and serum hormone concentrations decreased to low levels in rats placed on a high bulk non-nutritive diet over the same period. These results suggest that food in the gastrointestinal tract is necessary for the maintenance of normal serum and antral gastrin concentration in rats. The effect of food is most likely attributable to chemical constituents and not distention by bulk.

Topics: Animals; Cellulose; Diet; Fluorescent Antibody Technique; Gastrins; Male; Pyloric Antrum; Radioimmunoassay; Rats; Starvation

Topics: Animals; Eating; Female; Gastrins; Male; Radioimmunoassay; Starvation; Swine; Time Factors

Topics: Animals; Biological Assay; Blood Glucose; Body Weight; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Liver; Male; Organ Size; Pyloric Antrum; Rabbits; Starvation

Topics: Acetylcholine; Adenosine Triphosphate; Adenylyl Cyclase Inhibitors; Adenylyl Cyclases; Animals; Calcium; Cholecystokinin; Edetic Acid; Enzyme Activation; Epinephrine; Fluorides; Gastrins; Glucagon; Hydrogen-Ion Concentration; In Vitro Techniques; Kinetics; Magnesium; Male; Pancreas; Phosphorus Isotopes; Rats; Secretin; Starvation

Topics: Anesthetics; Animals; Biological Assay; Body Temperature; Gastric Juice; Gastric Lavage; Gastric Mucosa; Gastrins; Injections, Intraperitoneal; Injections, Intravenous; Methods; Rats; Secretory Rate; Sodium Chloride; Starvation; Stomach; Urethane