Table 1. Summary of experimental studies on glicentin functions and variation.
| Functions | Models | Aim | Main results | References |
|---|---|---|---|---|
| Factors stimulating glicentin secretion | Piglets - administration of butter, glycerol and sodium palmitate into the duodenum | Investigate the response of plasma glicentin to intraluminal fat loading. | Increase of plasma glicentin following butter and palmitate administration Slight increase of plasma glicentin, but not significant following glycerol administration |
Ohneda et al. (15) |
| Piglets - administration of a mixture of 10 amino acids into the duodenum Dogs - pancreatectomy, administration of arginine |
Explore the effect of amino acids on glicentin secretion. | Increase of plasma glicentin following amino acids administration Increase of total immunoreactive glucagon in pancreatectomized dogs following amino acids administration Administration of amino acids enhances glicentin secretion from the gut. |
Ohneda et al. (16) | |
| Piglets - administration of glucose into the duodenum | Investigate the secretion of glicentin in response to intraluminal administration of glucose. | Increase of plasma glicentin after glucose loading | Ohneda et al. (17) | |
| Effect of glicentin on intestinal trophicity | Rats - subcutaneous injection of glicentin (50 µg/kg every 12h for 2 weeks) In vitro - intestinal epithelial cell line IEC-6, incubation with glicentin (0–1000 ng/mL) for 48h |
Examine the trophic effects of glicentin on small-intestinal mucosa and on the small-intestinal epithelial cell line IEC-6 | Jejunum - increase of weight, protein, DNA content and alkaline phosphatase activity in animals who were injected with glicentin; increase of ornithine decarboxylase activity after intraperitoneal injection of glicentin Ileum - no difference between animals injected with glicentin and the control group In vitro - increase of tritium-thymidine incorporation and the number of IEC-6 cells in presence of glicentin Trophic effect of glicentin on intestinal mucosa. |
Myojo et al. (18) |
| Rats - parenteral nutrition for 6 days and administration of 1, 4, 20 or 80 µg/rat of glicentin via the jugular vein | Examine the effects of glicentin on intestinal proliferation in vivo in the rat. | Dose-dependent increase of mucosal proliferation in the small intestine induced by glicentin, with an effect more pronounced in the ileum Decreased crypt fission of the ileum in the 20 and 80 µg glicentin groups compared to controls No significant effect of glicentin on proliferation or fission in the colon Trophic effect of glicentin on the small intestine but not on the colon. |
Sasaki et al. (19) | |
| Rats - resection of the small intestine and aministration of methionyl rat glicentin (20 μ/day/rat) from the second day after the operation and during 28 days using miniosmotic pumps | Explore the effects of glicentin on intestinal adaptive responses to 70% resection of small intestine in rats | Rats with 70% distal intestinal resection - significant increase of the weight of the residual duodenum and its mucosal weight, protein, and diamine oxydase activity compared to controls. No significant change on the residual jejunum. Rats with 70% proximal intestinal resection - significant increase of the weight of the residual duodenum and its mucosal weight, protein, and diamine oxydase activity compared to controls Stimulating activity of glicentin on the adaptive responses to massive intestinal resection. |
Hirotani et al. (23) | |
| Rats - construction of loops of jejunum and ileal Thiry-Vella fistulas (TVFs) that were isolated from the luminal stream and subcutaneous injection of glicentin (50 µg/kg every 12 hours for 1 week) | Determine whether the trophic effect of glicentin is mediated by mechanism involving luminal or non-luminal factors and determine whether glicentin exerts a differential trophic effect on jejunal or ileal mucosa | Effect of glicentin in the jejunal TVF group - increase of mucosal growth measurements in the TVF and the intact jejunum Effects of glicentin on the proximal gut mucosa may be caused by a combination of non-luminal and luminal factors. Effect of glicentin in the ileal TVF group - stimulation of the proliferation of intact ileal mucosa but no effect on the ileal TVF Effect on the ileal mucosa may be influenced by luminal contents and endogenous secretions. Differential trophic effect of glicentin on mucosa of the proximal jejunum and distal ileum. |
Hashimoto et al. (24) | |
| Effect of glicentin on bacterial internalization and Helicobacter pylori infection | Cell line, in vitro INT-407 cell lines - incubation of glicentin (100 ng/ml to 1 µg/ml) for 24h Assays on bacterial internalization with Salmonella enteritidis IFO 3313, Escherichia coli ATCC M44 and Enterococcus faecalis ATCC 29212 |
Determine the effect of recombinant human glicentin on bacterial internalization by confluent enterocytes | Lower bacterial internalization through the glicentin-treated enterocytes than the non-treated Dose dependent effect of glicentin on bacterial internalization in the range from 500 to 1 µg/mL Glicentin acts as a barrier-sustaining agent that inhibits extra-intestinal invasion of enteric bacteria and decreased bacterial translocation. |
Chiba et al. (25) |
| Human gastric biopsies - 7 cases with endoscopical intestinal metaplasia; 47 cases with no endoscopical intestinal metaplasia 18 biopsies with histological intestinal metaplasia 29 biopsies with no intestinal metaplasia |
Investigate the relationship between Helicobacter pylori infection, intestinal metaplasia and glicentin expression in the gastric mucosa | Detection of mRNA glicentin expression in 100% of cases with endoscopical intestinal metaplasia, in 76,7% of cases with no endoscopical intestinal metaplasia Glicentin mRNA expression statistically associated with the existence of histological intestinal metaplasia and positively correlated with Helicobacter pylori infection |
Ishihara et al. (33) | |
| Effect of glicentin on gastro-intestinal motility | Rats - glicentin IV infusion during the 5 min preceding food onset and during the first 15 min of food intake | Investigate the effect of a systemic increase of glicentin on food intake, postprandial myoelectrical activity in duodenum, jejunum and ileum and the oro-caecal transit | No effect of systemic injection of glicentin on food intake Reduction of duration of the postprandial myoelectrical activity on duodenum and jejunum induced by glicentin |
Pellissier et al. (26) |
| Dogs - use of vagally denervated gastric pouches equipped with four strain gauge force transducers on the pouch, gastric body, antrum and duodenum. Injection of glicentin intra-veinously (1 nmol/kg) |
Explore the effect of glucagon, GLP-1, GLP-2 and glicentin on gastroduodenal motility and their mechanisms of action | Glicentin did not affect motilin-induced phase III contractions at any site Glucagon inhibited contractions in the pouch and the stomach GLP-1 inhibited contractions at all sites GLP-2 inhibited contractions in the pouch Differential effect of proglucagon-related peptides on gastroduodenal motility. |
Shibata et al. (48) | |
| Rabbit, in vitro - isolation of smooth muscle cells (SMCs) from rabbit antrum, incubation with glicentin (5 nmol/L) | Explore the effect of glicentin SMCs contraction isolated from the rabbit antrum | Induction of SMCs contraction by glicentin Maximal contraction at 30 s |
Rodier et al. (29) | |
| Rabbit, in vitro - isolation of SMCs from rabbit antrum, incubation with glicentin (2 nmol/L) | Describe the morphological and functional characteristics of a model of cultured digestive SMCs exhibiting a differentiated phenotype | Induction of SMCs contraction by glicentin | Jarousse et al. (30) | |
| Effect of glicentin on gastro-intestinal motility | Rabbit, in vitro - isolation of SMCs from rabbit antrum, incubation with glicentin (0.3 nmol/L) | Investigate the modifications of the calcium/ phosphoinositide and the cyclic adenosine monophosphate (cAMP) pathways in rabbit antral SMCs | Induction of SMCs contractions by glicentin Induction of a biphasic and rapid inositol (1, 4, 5)-trisphosphate (Ins(1,4,5)P3) production by glicentin In the absence of extracellular calcium: glicentin induced Ins(1,4,5)P3 production became monophasic Induction of a rapid increase of intracellular free calcium induced by glicentin Reduction of the cAMP content by glicentin of cells stimulated by forskolin Contractile effect of glicentin potentially mediated by stimulation of the phosphoinositide hydrolysis and inhibition of cAMP production Action of glicentin potentially mediated by receptor coupled to G proteins |
Rodier et al. (28) |
| Human, in vitro - 32 preparations of human normal jejunal muscle strips | Investigate the enteric nervous responses to glicentin in the normal small bowel | Inhibition of contraction reaction by glicentin after blockade of the adrenergic and cholinergic nerve Regulating inhibition of the contraction reaction in normal human jejunum via non-adrenergic non-cholinergic (NANC) nerves, and has a direct action on the jejunal muscle receptor. |
Tomita et al. (27) | |
| Human, in vitro patients who underwent resections for colon adenocarcinoma (8 right colons, 14 left colons); isolation of SMCs Rabbit - SMCs from antrum |
Investigate the effect of glicentin on the motor activity of colon | Human SMCs from colon - dose-related contraction of SMCs induced by glicentin. Decrease of contractile activity induced by glicentin when incubated with exendin- (9–39), a selective antagonist of GLP-1 receptor Rabbit SMCs from antrum - exendin- (9–39) dose dependently reduced the contractile activity of glicentin Effect of glicentin in SMC contraction may be mediated by GLP-1 receptor. |
Ayachi et al. (31) | |
| Effect of glicentin on gastric acid secretion | Rats - use of chronic gastric fistulas, stimulation of gastric acid secretion by pentagastrin, injection of glicentin intra-veinously (bolus 3µg/kg, followed by 600 ng/h or 120 ng/h) | Investigate the role of glicentin on gastric acid secretion | Inhibition of gastric acid secretion by glicentin | Kirkegaard et al. (32) |
| Effect of glicentin on glucose metabolism | Rats, in vitro - isolation of hepatocytes | Study the effect of glicentin on the glucose production and cAMP accumulation of isolated hepatocytes | Glicentin and glucagon stimulated the release of glucose from hepatocytes into the medium Stimulation of cAMP production by glucagon and glicentin Degradation of glicentin into low molecular weight fragments during incubation with hepatocytes, with some fragments similar to glucagon |
Thieden et al. (35) |
| Dogs - use of in vivo local circulation in canine pancreas; administration of glicentin into the pancreaticoduodenal artery (400 ng for 10 min) | Investigate the effect of glicentin-related peptides on the endocrine pancreatic function | Plasmatic concentrations after glicentin (1-16) administration in the canine pancreas - decrease of glucagon Plasmatic concentrations after glicentin (62-69) administration in the canine pancreas - decrease of insulin and glucagon Glicentin released during nutrient intake might inhibit the secretion of glucagon. |
Ohneda et al. (36) | |
| Dogs - use of in vivo local circulation in canine pancreas; administration of glicentin into the pancreaticoduodenal artery (200 pmol for 10 min) | Study the role of glicentin-related peptides on the endocrine pancreas | Plasmatic concentrations after glicentin (1-16) and glicentin (62-69) administration in the canine pancreas - increase of insulin and decrease of glucagon Plasmatic concentrations after glicentin (62-69) administration in the canine pancreas - increase of insulin and decrease of glucagon Maximum response of insulin and glucagon within 20 min after glicentin (1-16) and glicentin (62-69) administration - increase of insulin and decrease of glucagon |
Ohneda et al. (34) | |
| Dogs - use of in vivo local circulation in canine pancreas; administration of glicentin into the pancreaticoduodenal artery (100 and 400 pmol for 10 min) | Explore the effect of human recombinant glicentin on the endocrine function of the pancreas | Plasmatic concentrations after glicentin administration at a dose of 100 pmol during glucose infusion - no significant change in blood glucose, slight increase of insulin, but not significant; no significant change of glucagon Plasmatic concentrations after glicentin administration at a dose of 400 pmol during glucose infusion - significant increase of blood glucose, significant increase of insulin, increase of glucagon Plasmatic concentrations after glicentin administration at a dose of 100 pmol during arginine infusion - no significant change in blood glucose, significant increase of insulin, no significant change of glucagon Plasmatic concentrations after glicentin administration at a dose of 400 pmol during arginine infusion - no significant change in blood glucose, significant increase of insulin, increase of glucagon Demonstration of the insulinotropic action of glicentin. |
Ohneda et al. (37) | |
| GLP 1/2 - glucagon like peptide 1 and 2. | ||||