cholecystokinin and Starvation

Since the subject of intestinal adaptation was last reviewed (16, 20, 97), there have been relatively few major advances but many useful minor additions and extensions which have helped to consolidate our knowledge of the field. The aim of this chapter is to summarise the results of a series of experiments which build up to our present state of knowledge. In doing so, the results of relatively old studies carried out some 15 years ago are briefly reviewed since they provide an essential background for, our current work. However, the article concentrates mainly on the new developments and in discussing these, areas of doubt and controversy are emphasised.

Topics: Adaptation, Physiological; Animals; Biliary Tract; Biological Transport, Active; Cholecystokinin; Dogs; Female; Hormones; Humans; Hyperplasia; Intestinal Absorption; Intestinal Mucosa; Intestine, Small; Lactation; Pancreas; Parenteral Nutrition, Total; Pregnancy; Rats; Secretin; 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

Yangtze sturgeon (Acipenser dabryanus) is a species endemic to Yangtze River drainage in China and is listed as a critically endangered species on the IUCN Red List. In the present study, cholecystokinin (CCK), one of the most important neuroregulatory digestive genes, and its receptor (CCKr) were identified from the full-length transcriptome analysis of A. dabryanus. The deduced amino acid sequences of CCK and CCKr from A. dabryanus showed structural features common to those in other vertebrates. Gene expression profile analysis showed that CCK and CCKr were universally expressed in different tissues, and both had the highest expression in the brain. Starvation and refeeding significantly regulated the expression levels of CCK and CCKr in the brain, suggesting that CCK and CCKr were involved in feed intake regulation in A. dabryanus as in mammals. In addition, the expression levels of CCK and CCKr under different feeding frequencies were studied. Compared with the control group (fed two times a day), the expression levels of CCK and CCKr in the intestine and brain did not change significantly in the other groups after 8 weeks of rearing, indicating that the feeding frequency might not influence the appetite of A. dabryanus. The present work provides a basis for further investigation into the regulation of feeding in A. dabryanus.

Topics: Animals; Cholecystokinin; Endangered Species; Fishes; Mammals; Starvation; Tissue Distribution

Feeding is essential for animal survival and reproduction and is regulated by both internal states and external stimuli. However, little is known about how internal states influence the perception of external sensory cues that regulate feeding behavior. Here, we investigated the neuronal and molecular mechanisms behind nutritional state-mediated regulation of gustatory perception in control of feeding behavior in the brown planthopper and Drosophila. We found that feeding increases the expression of the cholecystokinin-like peptide, sulfakinin (SK), and the activity of a set of SK-expressing neurons. Starvation elevates the transcription of the sugar receptor Gr64f and SK negatively regulates the expression of Gr64f in both insects. Interestingly, we found that one of the two known SK receptors, CCKLR-17D3, is expressed by some of Gr64f-expressing neurons in the proboscis and proleg tarsi. Thus, we have identified SK as a neuropeptide signal in a neuronal circuitry that responds to food intake, and regulates feeding behavior by diminishing gustatory receptor gene expression and activity of sweet sensing GRNs. Our findings demonstrate one nutritional state-dependent pathway that modulates sweet perception and thereby feeding behavior, but our experiments cannot exclude further parallel pathways. Importantly, we show that the underlying mechanisms are conserved in the two distantly related insect species.

Topics: Animals; Brain; Carbohydrate Metabolism; Carbohydrates; Cholecystokinin; Drosophila melanogaster; Feeding Behavior; Gene Expression; Gene Expression Regulation; Hemiptera; Neurons; Neuropeptides; Receptors, Cell Surface; Starvation; Sugars; Taste; Taste Perception

Endocrine factors released from the central nervous system, gastrointestinal tract, adipose tissue and other peripheral organs mediate the regulation of food intake. Although many studies have evaluated the effect of fed-to-starved transition on the expression of appetite-related genes, little is known about how the expression of appetite-regulating peptides is regulated by the macronutrient composition of the diet. The aim of the present study was to examine the effect of diet composition and nutritional status on the expression of four peptides involved in food intake control in gilthead sea bream (Sparus aurata): neuropeptide Y (NPY), ghrelin, cholecystokinin (CCK) and leptin. Quantitative real-time RT-PCR showed that high protein/low carbohydrate diets stimulated the expression of CCK and ghrelin in the intestine and leptin in the adipose tissue, while downregulation of ghrelin and NPY mRNA levels was observed in the brain. Opposite effects were found for the expression of the four genes in fish fed low protein/high carbohydrate diets or after long-term starvation. Our findings indicate that the expression pattern of appetite-regulating peptides, particularly CCK and ghrelin, is modulated by the nutritional status and diet composition in S. aurata.

Topics: Animals; Body Composition; Body Weight; Cholecystokinin; Diet; Gene Expression Regulation; Ghrelin; Leptin; Linear Models; Neuropeptide Y; RNA, Messenger; Sea Bream; Starvation

Gastrointestinal (GI) peptide hormones, ghrelin (GHRL), cholecystokinin (CCK), and peptide YY (PYY) genes were identified in Atlantic salmon, Salmo salar. Full-length cDNAs encoding two isoforms of GHRL (GHRL-1 and GHRL-2), two isoforms of CCK (CCK-L and CCK-N) and peptide YY (PYY) cDNA were obtained. The GHRL-1 and GHRL-2 genes encoded proteins of 111- and 108-amino acids, respectively. Both types of GHRL were mainly expressed in the stomach, but also weakly expressed in the pyloric caeca, mid-gut, adipose tissue, and testis. The CCK-L and CCK-N genes encoded preproproteins of 132- and 140-amino acids, respectively. Both types of CCK were strongly expressed in the brain and comparatively weakly expressed in other tissues, including the digestive tract. In the digestive tract, CCK-L was mainly expressed in the pyloric caeca and hind-gut, while CCK-N was only expressed in the pyloric caeca. The PYY gene encoded for 97-amino acid residues and was mainly expressed in the brain and anterior part of the intestine, including the pyloric caeca. In an experiment, we demonstrated that 6 days starvation led to, increased GHRL-1 mRNA levels in the GI tract (stomach), while there no significant changes in expression levels for the other hormones in the GI tract. This suggests an orexigenic role for GHRL-1 in Atlantic salmon. These data contribute to elucidate the functional relationships among teleost gastrointestinal peptide hormones.

Topics: Amino Acid Sequence; Animals; Base Sequence; Cholecystokinin; Cloning, Molecular; DNA, Complementary; Fish Proteins; Ghrelin; Molecular Sequence Data; Peptide YY; Phylogeny; Salmo salar; Sequence Alignment; Sequence Analysis, DNA; Sequence Analysis, Protein; 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 mechanism behind the possible feedback regulation of pancreatic exocrine secretion is not well understood.. Thirteen minipigs were prepared with fistulas to the pancreatic duct and the duodenum. Peripheral venous blood was obtained for determination of secretin and cholecystokinin (CCK) levels. Four different experiments were performed: 1) diversion and reinfusion of pancreatic juice; 2) intraduodenal infusion of NaHCO3 solution, with the same volume, bicarbonate concentration, and osmolality as the collected pancreatic secretion, and reinfusion of pancreatic juice; 3) reinfusion of pancreatic secretion for 1 h before and 2 h after a meal; and 4) diversion of pancreatic secretion and intraduodenal infusion of NaHCO33 solutions before and after a meal.. Reinfusing pancreatic juice significantly decreased pancreatic juice volume and bicarbonate output and slightly decreased the level of secretin in plasma. Alternating infusions of substitute NaHCO3 and pancreatic juice did not change pancreatic output of bicarbonate and protein, nor did it change the CCK and secretin levels in plasma. Replacing pancreatic juice with intraduodenal NaHCO3 infusions during a meal did not significantly modify the pancreatic secretion of bicarbonate and protein or the hormonal levels in blood.. A negative feedback regulation of pancreatic exocrine secretion is present in starved minipigs. Duodenal acidity and plasma levels of secretin semm to be of importance, whereas duodenal enzyme activity and the level of CCK in plasma probably are not. A postprandial negative feedback regulation through duodenal enzymatic activity and release of CCK into blood could not be shown.

Topics: Animals; Cholecystokinin; Duodenal Diseases; Feedback; Food; Intestinal Fistula; Pancreas; Pancreatic Fistula; Pancreatic Juice; Secretin; Sodium Bicarbonate; Starvation; Swine; Swine, Miniature

The purpose of the present study was to examine the weight, DNA content, and enzyme mRNA levels in the pancreas in response to endogenous hypercholecystokininemia produced by pancreaticobiliary diversion (PBD) in starved rats. The results showed that PBD, which is known to increase the circulating cholecystokinin (CCK) concentration, prevented the reduction in the weight and DNA content of the pancreas after 3 days of starving, and that PBD increased the mRNA levels of amylase, chymotrypsinogen B, and procarboxypeptidase A in the pancreas of starved rats. The findings support the view that endogenous CCK plays an important role in maintaining the weight of the normal pancreas of starved rats and that it stimulates the transcription of genes coding for pancreatic exocrine enzymes.

Topics: Actins; Amylases; Animals; Biliopancreatic Diversion; Carboxypeptidases; Carboxypeptidases A; Cholecystokinin; Chymotrypsinogen; DNA; Enzyme Precursors; Male; Pancreas; Rats; Rats, Sprague-Dawley; RNA, Messenger; Starvation

Antibacterial activity of pancreatic juice in the pig (n = 8) was investigated during early postnatal development and in cattle (n = 6) receiving a different feeding regimen. For pancreatic juice collection, a catheter was surgically implanted in the pancreatic duct. Reintroduction of pancreatic juice was achieved through a T-shaped cannula in the duodenum. Pancreatic juice was collected for 30 min in all cases. In piglets, collections were carried out at 2, 5-6, and 7-10 wk of age, and in cattle, after a standard meal, 48 h starvation, and following 24 h intraduodenal glucose infusion. Antibacterial activity was tested on Micrococcus Pyogenes strain ATTC 6538P by disc agar diffusion technique using nonactivated pancreatic juice, before and after heat treatment for 15 min at 65 and 100 degrees C, respectively. Piglets showed a significant rise in antibacterial activity of pancreatic juice after weaning. In cattle, 48 h of starvation resulted in a marked suppression of antibacterial activity. This activity was found to be normal after a standard meal and comparable to that after 24-h intraduodenal glucose infusion. Heating of pancreatic juice to 65 degrees C caused a 35% increase in the antibacterial potency, whereas heating to 100 degrees C completely abolished it. Additionally, dilution of pancreatic juice to 1:10 did not affect antibacterial potency.

Topics: Aging; Animals; Bacteria; Cattle; Cholecystokinin; Dietary Carbohydrates; Female; Food; Glucose; Hydrogen-Ion Concentration; Male; Pancreatic Juice; Starvation; Swine

The concentration of cholecystokinin (the octapeptide, CCK-8), bombesin, and neurotensin was measured by radioimmunoassay in the cortex, hypothalamus and diencephalon of brains from lean, genetically obese and hypothalamic (VMH) obese rodents. Highest concentration of CCK-8 was found in the cortex whereas highest concentrations of bombesin and neurotensin were in the hypothalamus. When food was provided ad libitum, there was no difference in concentration of any of these peptides between lean and the respective genetically obese mice (ob/ob) and fatty (fa/fa) rats, or between lean and hypothalamic (VMH lesioned) obese rats. Adrenalectomy, which arrested the progression of obesity in both ob/ob and fatty rats, did not result in significant change in concentration of any of the three peptides studied in comparison with the respective sham-operated animals. Though significant differences in cholecystokinin and bombesin concentrations were detectable in some instances between adrenalectomized lean and adrenalectomized obese rats, these differences did not appear to be related to fall in food intake or slowing of body weight gain. Thus a variety of manipulations which altered the nutritional plane of the experimental rodents was not accompanied by significant changes in brain concentrations of cholecystokinin, bombesin or neurotensin.

Topics: Adrenal Glands; Animals; Appetite Regulation; Bombesin; Brain Chemistry; Cerebral Cortex; Cholecystokinin; Diencephalon; Female; Hypothalamus; Mice; Mice, Obese; Neurotensin; Obesity; Peptides; Rats; Rats, Inbred Strains; Rats, Zucker; Starvation; Ventromedial Hypothalamic Nucleus

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

1. This study examines the influence of starvation on intestinal CCK content and pancreatic growth. Intestinal CCK content was determined by measuring the CCK-like activity using an in vitro gall-bladder bio-assay. Starvation for up to 72 hr causes a parallel fall in intestinal CCK content and pancreatic DNA synthesis. Since there was no significant decrease in liver DNA synthesis, the effect of starvation was probably not simply a consequence of malnutrition. Furthermore there was little effect of starvation on pancreatic protein and DNA content, suggesting that pancreatic cell turnover is particularly sensitive to changes in dietary stimulation.2. With refeeding after starvation CCK-like activity in intestinal extracts gradually increased, approaching non-fasting levels 72 hr after refeeding. Pancreatic DNA synthesis also returned to non-fasting levels after feeding but this rose faster than the intestinal CCK content.3. Pentagastrin treatment prevented the atrophy of both the pancreas and the gastrointestinal tract with starvation without influencing the fall in intestinal CCK-like activity. This suggests that the control of CCK-containing cells is different from that of the surrounding intestinal parenchyma.4. The effect of starvation was also studied in antrectomized rats. Antrectomy alone did not reduce pancreatic DNA synthesis although DNA synthesis of the small intestine was significantly reduced. When antrectomized rats were starved pancreatic DNA synthesis fell to the same degree as was found in unoperated animals. The pancreatic atrophy was also accompanied by a drop in intestinal CCK content. Starvation of antrectomized rats, however, did not further depress the already greatly reduced plasma gastrin concentration.

Topics: Animals; Atrophy; Biological Assay; Cholecystokinin; DNA; Intestine, Small; Liver; Male; Pancreas; Pentagastrin; Rats; Starvation

Cholecystokinin-like immunoreactivity (CCK-LI) was demonstrated by radioimmunoassay in aqueous (n = 3) and acid (n = 10) extracts of cortex (42 +/- 9 pmol/g; 4.0 +/- 1.8 pmol/g), thalamus (4.1 +/- 1.1 pmol/g; 1.0 +/- 0.2 pmol/g), and hypothalamus (58 +/- 14 pmol/g; 6.3 +/- 0.7 pmol/g). Sephadex chromatography revealed that more than 95% of the immunoreactivity in acid extracts coeluted with CCK33 standard. In aqueous extracts more than 80% of immunoreactivity coeluted with CCK8 standard. Both the CCK33- and CCK8-like materials induced contraction of guinea pig gallbladder in vitro. L-Tryptophan (200 mg/kg) and high-dose morphine (20 mg/kg) decreased CCK33-LI concentrations in hypothalamus and thalamus. Low-dose morphine (5 mg/kg) decreased CCK33-LI in hypothalamus. We conclude that 1) CCK-LI is present in cortex, thalamus, and hypothalamus of the rat brain, 2) CCK-LI exists in two predominant molecular forms coeluting with CCK33 and CCK8, 3) both molecular forms are biologically active, and 4) concentrations of rat brain CCK33-LI are modulated by serotonergic and opiate mechanisms.

Topics: Animals; Brain; Cholecystokinin; Chromatography, Gel; Clonidine; Cold Temperature; Dose-Response Relationship, Drug; Fluorescent Antibody Technique; Histocytochemistry; Morphine; Rats; Starvation; Structure-Activity Relationship

Topics: Amylases; Animals; Carbachol; Cholecystokinin; Diazoxide; Dinitrophenols; Female; Glucose; Glyburide; Insulin; Mice; Nutritional Physiological Phenomena; Organ Size; Pancreas; Parotid Gland; Starvation

Topics: Amylases; Animals; Bile Ducts; Catheterization; Cholecystokinin; Chromatography, Ion Exchange; Cyclic AMP; Cyclic GMP; Gastrointestinal Hormones; Intestines; Male; Pancreas; Peptides; Pilocarpine; Radioimmunoassay; Radioligand Assay; Rats; Secretin; Starvation; Time Factors

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