Biomedical subjects

T E Adrian

Publications and source records attributed to T E Adrian.

At least 55 records · Page 3Linked to original sources

PubMed1998

In vitro influences between pancreatic adenocarcinoma cells and pancreatic islets.

BACKGROUND: Interactions have been found between exocrine pancreatic adenocarcinoma and islets of Langerhans. Growth of pancreatic adenocarcinoma cells can be regulated by islet hormones such as insulin and somatostatin. Conversely, dysfunction of endocrine pancreas frequently accompanies the exocrine malignancy. The mechanisms underlying these interactions have not been defined. MATERIALS AND METHODS: Human pancreatic adenocarcinoma cells (HPAF cells) were cocultured with isolated rat pancreatic islets in two-compartment wells. HPAF cells and islets cultured in separate wells served as controls. In separate experiments, HPAF cells were incubated with two concentrations of exogenous insulin, including one reflecting the levels of insulin secretion seen in the coculture experiments. RESULTS: Proliferation of HPAF cells was increased by about 50% following a 2- or 5-day incubation with pancreatic islets (P < 0.05). Coculture of HPAF cells and pancreatic islets was associated with a greater reduction in glucose concentrations (P < 0. 01) and an increase in lactate accumulation (P < 0.05) in the culture media. Insulin concentrations in the media were significantly decreased during the first 2-3 days of the coculture incubation (P < 0.05). In contrast, insulin secretion from control islets was not significantly decreased until the fifth day of the experiment. The growth of HPAF cells was stimulated by both concentrations of exogenous insulin (P < 0.05). The insulin-stimulated HPAF cells also showed an enhanced glucose consumption and lactate production (P < 0.05). CONCLUSIONS: Pancreatic islets regulate both growth and glucose metabolism of adjacent exocrine cancer cells. beta-cell-derived insulin may be one of the factors inducing these effects. Insulin release from islet beta-cells is compromised in the presence of exocrine cancer cells.

Adenocarcinoma↗

PubMed1998

Ileoanal pouch function and release of peptide YY.

PURPOSE: This study evaluates peptide tyrosine-tyrosine (PYY), intestinal transit, fecal retention time, and anal sphincter manometry in colectomized patients with ileal pouch-anal anastomosis. METHODS: Plasma and pouch PYY, mouth-to-pouch transit time, fecal retention time, and anal canal pressures were studied in 27 patients with ileoanal pouches a mean of 50 (range, 3-84) months after loop ileostomy closure. RESULTS: Basal and peak postprandial plasma PYY were significantly reduced in patients with pouches compared with controls (P < 0.0001). Pouch PYY was decreased compared with control ileal PYY (P = 0.0003). No significant correlation was noted between intestinal transit and total integrated PYY response in patients with pouches (r=0.36; P=0.06). Fecal retention time was related to postprandial total integrated response of plasma PYY (r=0.43; P=0.02), mouth-to-pouch transit (r=0.87; P < 0.0001), and resting (r=0.44; P=0.02) and squeeze (r=0.62; P=0.0006) anal sphincter pressures. CONCLUSIONS: Colectomized ileoanal patients with pouches showed decreased plasma and pouch PYY compared with controls. Intestinal transit was not significantly related to PYY release. However, prolonged pouch fecal retention was associated with greater PYY release, mouth-to-pouch transit, and anal sphincter pressures.

Adolescent↗

PubMed1998

Effects of epidermal growth factor on neonatal pancreatic growth in the guinea pig.

CONCLUSION: EGF and/or transforming growth factor-alpha (TGF-alpha) are likely to be important in the rapid pancreatic growth that occurs in the neonatal guinea pig. BACKGROUND: Rapid pancreatic growth is observed during the neonatal period in the guinea pig. The growth factors that are involved are not known but may include members of the EGF family. METHODS: Mini-osmotic pumps were implanted on the day of birth for continuous infusion of EGF (30 microgram/d). Pancreatic DNA, RNA, and protein contents were determined at 4 and 15 d, along with wet weights of the pancreas, duodenum, jejunoileum, colon, and gallbladder. Pancreatic EGF and TGF-alpha concentrations were measured in adult controls, in control neonates at 1, 4, 8, and 15 d, and also at 4 and 15 in guinea pigs receiving either EGF or the cholecystokinin receptor antagonist devazepide (25 nmol/kg/h). RESULTS: EGF infusion significantly increased the weight of the stomach and duodenum at 4 d and all the gastrointestinal organs, including the pancreas, at 15 d. Exogenous EGF increased pancreatic DNA, RNA, and protein content at 4 and 15 d. Endogenous EGF and TGF-alpha concentrations in the pancreas were significantly higher at birth than in adults (P < 0.001) and P < 0.01, respectively) and declined during the first 2 wk postpartum. At 15 d, EGF concentrations remained significantly higher than adult levels (P < 0.01), but TGF-alpha concentrations had declined to adult values. Infusion of EGF decreased concentrations of endogenous EGF in the pancreas at 4 and 15 d (both P < 0.05) and decreased TGF-alpha concentrations at 4 d (P < 0.001). Devazepide infusion caused a significant decrease in endogenous pancreatic EGF concentrations at 15 d (P < 0.05).

Aging↗

PubMed1998

Pancreatic cancer cells selectively stimulate islet beta cells to secrete amylin.

BACKGROUND & AIMS: Patients with pancreatic adenocarcinoma have a high incidence of diabetes, profound insulin resistance, and high circulating amylin concentrations. It was hypothesized that pancreatic cancer cells produce a factor that stimulates islets to secrete amylin but not insulin. METHODS: Amylin and insulin secretion were measured after coculture of pancreatic cancer cells with beta cells (BRIN-BD11). The factor responsible was characterized by exposing beta cells to cancer cell-conditioned medium. RESULTS: Coculture with pancreatic (PANC-1 HPAF, and MiaPaCa2) but not colonic cancer cells (Colo 320) significantly increased amylin secretion but did not change insulin output. This effect was both time and cell number dependent. Coculture with PANC-1 or HPAF cells significantly decreased intracellular amylin, but not insulin, content. PANC-1 or HPAF cell-conditioned medium also increased amylin secretion and decreased intracellular amylin content. The factor responsible was extracted under both neutral and acidic conditions, was heat labile, and had a molecular weight of approximately 1500. CONCLUSIONS: A soluble factor from pancreatic cancer cells selectively stimulates amylin secretion from islet cells, explaining the excessive amylin secretion found in pancreatic cancer. Because elevation of amylin concentration is an early feature of pancreatic cancer, characterization and measurement of the tumor-derived amylin-releasing factor might be valuable in the early detection of this disease.

Adenocarcinoma↗

PubMed1998

Qualitative changes in enteric flora and short-chain fatty acids after intestinal resection.

Our aim was to determine the effect of intestinal transection and resection on the prevalence of enteric flora and evaluate whether any such changes alter luminal SCFA and lactic acid content. Dogs underwent either 50% proximal (PR, N = 6) or distal (DR, N = 7) resection, distal resection with bypass of the ileocecal junction (DRBP, N = 9) or midpoint transection alone performed to serve as the appropriate control for luminal sampling for either proximal (PTC, N = 6) or distal (DTC, N = 7) resection. Studies were performed every four weeks for 12 weeks. Both jejunum and ileum had >10(5)/ml aerobic bacteria, most commonly E. coli. Streptococcal species were more common in the normal jejunum than ileum but were found in the ileal remnant after PR. Significant (>10(5)) anaerobic growth occurred infrequently in the jejunum, and DR did not increase anaerobic growth in jejunum unless DRBP was performed (93% vs 62% DR, 45% DTC, 20% normal jejunum, P < 0.05). Clostridium species increased significantly in the jejunal remnant after DRBP. Significant anaerobic growth occurred infrequently in normal ileum but increased after PR (89% vs 50% PTC, P < 0.05). Flora normally found in the jejunum tended to increase in the ileum after PR. Jejunal SCFA increased after DRBP (3126 +/- 577 microg/ml vs 1600 +/- 301 DTC, P < 0.05) but not DR (1791 +/- 321 microg/ml). Significant (>10(5)) anaerobic bacterial growth was associated with increased SCFA content (2717 +/- 381 vs 1029 +/- 170 microg/ml, P < 0.05) and the presence of lactic acid (30% vs 5%, P < 0.05), but there was no correlation between the presence of specific bacteria and SCFA and lactic acid. Following resection of the proximal small intestine, the intestinal remnant tends to assume the bacteriologic characteristics of the resected segment. Following a distal resection, the presence of an intact ICJ protects against the proliferation of a flora characteristic of the distal intestine; resection with bypass of the ICJ results in the appearance of coliforms in the jejunal remnant. These changes in enteric flora do not correlate with content of specific SCFA and lactic acid in the small intestine.

Animals↗

PubMed1998

An increase in mucosal insulin-like growth factor II content in postresectional rat intestine suggests autocrine or paracrine growth stimulation.

BACKGROUND: Luminal nutrients and growth factors regulate postresectional intestinal growth. The interplay between glutamine and regulatory gastrointestinal peptides is not known. METHODS: The effects of intestinal resection on tissue and plasma concentrations of peptides were studied in 60 Sprague-Dawley rats divided into resected, transected, or unoperated groups. Subgroups were fed either a glutamine-free or a glutamine-supplemented diet for 7 days. Epidermal growth factor, transforming growth factor-alpha, insulin-like growth factors (IGF) I and II, peptide YY (PYY), and enteroglucagon were analyzed in intestinal mucosa and in portal plasma by radioimmunoassay. RESULTS: No glutamine-specific effects were seen. The mucosal content of IGF-II (P < 0.01) and the portal levels of enteroglucagon and PYY (P < 0.05-0.01) increased after intestinal resection. CONCLUSIONS: The increase in PYY and enteroglucagon in portal blood supports a hormonal role in the postresectional adaptation. The increase in IGF II in the ileal mucosa, without changes in plasma, implies autocrine or paracrine growth stimulation at this stage after resection.

Adaptation, Physiological↗

PubMed1998

The intracellular mechanism of insulin resistance in the hamster pancreatic ductal adenocarcinoma model.

Diabetes associated with pancreatic cancer is characterized by profound peripheral insulin resistance. The intracellular mechanism of insulin resistance was investigated in skeletal muscles from N-nitrosobis(2-oxopropyl)amine (BOP)-treated hamsters. Effects of high-fat diet and exercise also were studied. BOP (20 mg/kg body weight) was administrated weekly for 2 weeks. Hyperinsulinemia was found in BOP-treated hamsters at 20 weeks after BOP treatment, suggesting the peripheral insulin resistance is an early feature in pancreatic cancer. Hamsters were killed at 42 weeks, and soleus muscles were taken for the analysis. Skeletal muscle insulin-receptor binding and insulin receptor tyrosine kinase activities were similar between the control and BOP-treated hamsters. However, maximal muscle glycogen synthase activity was significantly reduced in BOP-treated hamsters compared with the control group. Muscle glycogen phosphorylase activity was increased in the BOP-treated group fed with high-fat diet as well as in BOP-treated groups with exercise. These findings indicate that insulin resistance in the hamster pancreatic cancer model is caused by a postreceptor defect, which led to significant decrease of muscle glycogen synthase activity. Whereas a high-fat diet causes more severe insulin resistance in BOP-treated hamsters, high-fat diet and exercising had no significant effects on skeletal muscle insulin-receptor function and glycogen synthase activity. Furthermore, both high-fat diet and exercise enhanced glycogen phosphorylase activity in BOP-treated hamsters.

Adenocarcinoma↗

PubMed1998

Life threatening diarrhoea ultimately cured by surgery.

A 30-year-old previously healthy woman was diagnosed as having a vasoactive intestinal polypeptide (VIP)-producing tumour of the pancreas. Her medical history was typical for neuroendocrine gastrointestinal tumours, presenting initially with non-specific symptoms but eventually she developed life-threatening manifestations requiring intensive care due to severe dehydration. She immediately recovered following surgical resection. The patient had elevated serum concentrations of VIP as well as pancreastatin, and post-operatively elevated concentrations of three growth factors, IGF-I, EGF and TGF-alpha, were seen. The importance of the alterations in plasma concentrations of the different peptides for her symptomatology are discussed.

Adult↗

PubMed1998

Sufficiency of postprandial plasma levels of islet amyloid polypeptide for suppression of feeding in rats.

Our objective was to study whether islet amyloid polypeptide (IAPP) produces satiety by an endocrine mechanism. We used a rat model to determine whether postprandial plasma levels of IAPP are comparable to those required to inhibit feeding when IAPP is administered by continuous intravenous infusion. Food intake in rats with aortic catheters increased plasma IAPP levels from a fasting level of 10.8 +/- 0.5 pM to a peak level of 19.0 +/- 1.0 pM at 2.2 +/- 0.5 h. In rats with jugular vein and aortic catheters, the threshold intravenous dose for IAPP suppression of feeding was between 1 and 3 pmol . kg-1 . min-1. The 3 pmol . kg-1 . min-1 dose decreased 4-h intake by approximately 25% by decreasing meal frequency rather than meal size. This dose increased plasma IAPP by approximately 24 pM. These results suggest that postprandial plasma levels of IAPP are not quite sufficient to independently produce satiety.

Amyloid↗

PubMed1998

Effects of epidermal growth factor, cholecystokinin, and secretin on growth of the alimentary tract in the neonatal guinea pig.

Gut hormones and growth factors are likely to be involved in the functional changes and substantial growth of the alimentary tract that occurs during early neonatal life. The present experiments investigated the effects of continuous subcutaneous infusion of cholecystokinin (CCK), secretin, and epidermal growth factor (EGF) in neonatal guinea pigs for 4 or 15 days. At doses of 20, 100 or 500 pmol/kg/h, CCK and secretin had no effect on alimentary tract organs except for an increase in pancreatic weight at 4 days with the highest dose of CCK and an increase in stomach weight at 4 days with the highest dose of secretin. In contrast, EGF showed dose-dependent and time-dependent effects on all the alimentary tract organs when infused at 70, 210 and 630 pmol/kg/h. These results suggest that EGF, but not CCK or secretin, is likely to be an important trophic factor during the neonatal period.

Animals↗

PubMed1998

Insulin secretion is inhibited by subtype five somatostatin receptor in the mouse.

BACKGROUND: Recently five somatostatin receptor subtypes (SSTRs) were cloned, allowing the development of highly specific agonists to these SSTRs. Previous studies have shown a species specificity phenomenon with respect to the inhibition of insulin secretion by these selective agonists. This study was undertaken to determine which SSTR (2 or 5) is responsible for the inhibitory effect of somatostatin on glucose-stimulated mouse insulin secretion. METHODS: Intact mouse islets (n = 10) were stimulated with D-glucose in the presence or absence of receptor-specific somatostatin agonists. RESULTS: D-glucose (16.7 mmol/L) augmented insulin secretion by 158% above that seen with 3.9 mmol/L D-glucose. In the presence of DC 32-92 (SSTR5) selective agonist, D-glucose (16.7 mmol/L) augmented insulin secretion by 64% above that seen with 3.9 mmol/L D-glucose. The presence of SSTR 5 selective agonist resulted in a significant (P < .05) inhibition of glucose-stimulated insulin secretion. The identification of SSTR5 within the mouse pancreas was established by reverse transcriptase polymerase chain reaction and confirmed by Southern blot analysis. CONCLUSIONS: These results suggest that the inhibitory effect of somatostatin on insulin secretion is mediated through the subtype 5 receptor within the mouse islet.

Animals↗

PubMed1997

In vitro pancreatic ductal cell carcinogenesis.

Our experiments were designed to identify initial biochemical and biological changes that occur during pancreatic carcinogenesis. TAKA-1, an immortal hamster pancreatic ductal cell line, was treated in vitro for up to 11 weeks with the pancreatic carcinogen N-nitorosobis(2-oxopropyl)amine (BOP). These treated cells were designated TAKA-1 + BOP. The growth of TAKA-1 and TAKA-1 + BOP cell lines was investigated in soft agar and in hamsters intradermally. The resulting tumor from TAKA-1 + BOP was re-cultured in vitro and designated TAKA-1 + BOP-T. Mutation of c-K-ras and p53 oncogenes, chromosomal changes, expression of transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) receptor and several biochemical markers were examined in all cell lines. TAKA-1 + BOP but not TAKA-1 cells grew in soft agar and produced an invasive tumor in vivo. However, there were no differences in cell growth rate, DNA flow cytometry, or immunohistochemical findings between the non-transformed and transformed cells. TAKA-1, TAKA-1 + BOP and TAKA-1 + BOP-T cells all expressed mRNA of TGF-alpha and EGF receptor in a comparable pattern. DNA sequence analysis following polymerase chain reaction showed that neither TAKA-1 nor TAKA-1 + BOP cells has a mutation of c-K-ras or p53. Karyotype analysis demonstrated that TAKA-1 + BOP cells had more chromosomal abnormalities compared with TAKA-1 cells. Mutation of c-K-ras and p53 was not essential for carcinogenesis in hamster pancreatic ductal cells in vitro. In conclusion, immortality of the TAKA-1 cells caused expression of TGF-alpha to the same extent as in malignant cells. Chromosomal and ultrastructural patterns were the only differences detected between the non-transformed and BOP-transformed cells.

Amino Acid Sequence↗

PubMed1997

Structure-activity studies on position 14 of human alpha-calcitonin gene-related peptide.

A structure-activity study was performed to examine the role of position 14 of human alpha-calcitonin gene-related peptide (h-alpha-CGRP) in activating the CGRP receptor. Interestingly, position 14 of h-alpha-CGRP contains a glycyl residue and is part of an alpha-helix spanning residues 8-18. Analogues [Ala14]-h-alpha-CGRP, [Aib14]-h-alpha-CGRP, [Asp14]-h-alpha-CGRP, [Asn14]-h-alpha-CGRP, and [Pro14]-h-alpha-CGRP were synthesized by solid phase peptide methodology and purified by RP-HPLC. Secondary structure was measured by circular dichroism spectroscopy. Agonist activities were determined as the analogues' ability to stimulate amylase secretion from guinea pig pancreatic acini and to relax precontracted porcine coronary arteries. Analogues [Ala14]-h-alpha-CGRP, [Aib14]-h-alpha-CGRP, [Asp14]-h-alpha-CGRP, and [Asn14]-h-alpha-CGRP, all containing residues with a high helical propensity in position 14, were potent full agonists compared to h-alpha-CGRP in both tissues. Interestingly, replacement of Gly14 of h-alpha-CGRP with these residues did not substantially increase the helical content of these analogues. [Pro14]-h-alpha-CGRP, predictably, has significantly lower helical content and is a 20-fold less potent agonist on coronary artery, known to contain CGRP-1 receptor subtypes, and an antagonist on pancreatic acini, known to contain CGRP-2 receptor subtypes. In conclusion, the residue in position 14 plays a structural role in stabilizing the alpha-helix spanning residues 8-18. The alpha-helix is crucial for maintaining highly potent agonist effects of h-alpha-CGRP at CGRP receptors. The wide variety of functional groups that can be tolerated in position 14 with no substantial modification of agonist effects suggests the residue in this position is not in contact with the CGRP receptor. [Pro14]-h-alpha-CGRP may be a useful pharmacological tool to distinguish between CGRP-1 and CGRP-2 receptor subtypes.

Amino Acid Sequence↗

PubMed1997

Purification and characterization of islet hormones (insulin, glucagon, pancreatic, polypeptide and somatostatin) from the Burmese python, Python molurus.

Insulin was purified from an extract of the pancreas of the Burmese python, Python molurus (Squamata:Serpentes) and its primary structure established as: A Chain: Gly-Ile-Val-Glu-Gln-Cys-Cys-Glu-Asn-Thr10-Cys-Ser-Leu-Tyr-Glu-Leu- Glu-Asn-Tyr-Cys20-Asn. B-Chain: Ala-Pro-Asn-Gln-His-Leu-Cys-Gly-Ser-His10-Leu-Val-Glu-Ala-Leu-Tyr- Leu-Val-Cys-Gly20-Asp-Arg-Gly-Phe-Tyr-Tyr-Ser-Pro-Arg-Ser30. With the exception of the conservative substitution Phe --> Tyr at position B25, those residues in human insulin that comprise the receptor-binding and those residues involved in dimer and hexamer formation are fully conserved in python insulin. Python insulin was slightly more potent (1.8-fold) than human insulin in inhibiting the binding of [125I-Tyr-A14] insulin to the soluble full-length recombinant human insulin receptor but was slightly less potent (1.5-fold) than human insulin for inhibiting binding to the secreted extracellular domain of the receptor. The primary structure of python glucagon contains only one amino acid substitution (Ser28 --> Asn) compared with turtle/duck glucagon and python somatostatin is identical to that of mammalian somatostatin-14. In contrast, python pancreatic polypeptide (Arg-Ile-Ala-Pro-Val-Phe-Pro-Gly-Lys-Asp10-Glu-Leu-Ala-Lys-Phe- Tyr20-Thr-Glu-Leu-Gln-Gln-Tyr-Leu-Asn-Ser-Ile30-Asn-Arg-Pro-Arg -Phe.NH2) contains only 35 instead of the customary 36 residues and the amino acid sequence of this peptide has been poorly conserved between reptiles and birds (18 substitutions compared with alligator and 20 substitutions compared with chicken).

Amino Acid Sequence↗

PubMed1997

Dissociated secretion of islet amyloid polypeptide and insulin in serum-free culture media conditioned by human pancreatic adenocarcinoma cell lines.

CONCLUSION: The cosecretion of insulin and islet amyloid polypeptide (IAPP) is altered when isolated rat pancreatic islets are incubated in culture media conditioned by human pancreatic cancer cells. BACKGROUND: Pancreatic cancer is usually associated with impaired glucose tolerance. This study investigates the tumor-derived influence on beta-cell secretion of pancreatic islets. METHODS: Four conditioned media were prepared from two human pancreatic cancer cell lines (Panc-1 and HPAF), a hamster pancreatic cancer cell line (PC-1), and a fibroblast cell line (Ag1523). Isolated rat pancreatic islets were incubated first in the conditioned media or nonconditioned control medium for 24 h, then in the same kind of media containing 100 microM carbamylcholine for 90 min. Insulin and IAPP secretion were measured by radioimmunoassay. RESULTS: Islets in media conditioned by Panc-1 and HPAF cells demonstrated dissociation of insulin and IAPP secretion. During 24-h incubation, the dissociation was expressed as selectively decreased insulin secretion. With addition of 100 microM carbamylcholine, the dissociation was expressed as normal secretion of insulin and hypersecretion of IAPP. As a result, the IAPP/insulin molar ratios were increased in both groups during both time periods. The islets in PC-1 and Ag1523 media did not show any significant changes in insulin and IAPP secretion.

Adenocarcinoma↗

PubMed1997

Tachykinins (substance P, neurokinin A and neuropeptide gamma) and neurotensin from the intestine of the Burmese python, Python molurus.

Peptides with substance P-like immunoreactivity, neurokinin A-like immunoreactivity and neurotensin-like immunoreactivity were isolated in pure form from an extract of the intestine of the Burmese python (Python molurus). The primary structure of python substance P (Arg-Pro-Arg-Pro-Gln-Gln-Phe-Tyr-Gly-Leu- Met-NH2) shows one amino acid substitution (Phe8-->Tyr) compared with chicken/alligator substance P and an additional substitution (Lys3-->Arg) as compared with mammalian substance P. The neurokinin A-like immunoreactivity was separated into two components. Python neuropeptide gamma (Asp-Ala-Gly-Tyr- Ser-Pro-Leu-Ser-His-Lys-Arg-His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2 shows three substitutions (Gly5-->Ser, Gln6-->Pro and Ile7-->Leu) compared with alligator neuropeptide gamma and an additional substitution (His4-->Tyr) compared with mammalian neuropeptide gamma. Python neurokinin A (His-Lys-Thr-Asp-Ser-Phe-Val-Gly- Leu-Met.NH2) is identical to human/chicken/alligator neurokinin A. Python neurotensin (pGlu-Leu-Val-His-Asn-Lys-Ala-Arg-Pro-Tyr-Ile-Leu) is identical to chicken/alligator neurotensin. The data are indicative of differential evolutionary pressure to conserve the amino acid sequences of reptilian gastrointestinal peptides.

Animals↗

PubMed1997

Meal-induced secretion of gastrointestinal regulatory peptides is not affected by sleep.

UNLABELLED: The mechanisms responsible for the disruption of the migrating motor complex (MMC) by feeding are not fully understood. Sleep reduces the duration of the postprandial or fed pattern of motility in the intestine. This study was set out to determine if this effect is associated with sleep-induced changes in the secretion of regulatory peptides in response to food. METHODS: Duodenojejunal motility was studied in 15 healthy ambulant subjects for 2 consecutive days. On one day identical solid meals were consumed in the morning and late in the evening, the latter followed by sleep. On the other day, identical liquid meals were infused into the stomach and the duodenum in the morning and late in the evening, the latter after the onset of sleep. Plasma concentrations of gastrin, neurotensin, peptide YY (PYY), pancreatic polypeptide (PP), motilin and glucose were monitored before and after meals. Sleep significantly shortened the duration of the fed pattern after the solid meal and even more so after the liquid meal. The plasma concentrations of all peptides, except motilin, increased significantly following each meal. Blood glucose levels rose after each meal, the changes being similar with all meals. Food-induced gastrointestinal regulatory peptides secretion and intestinal absorption of glucose are not affected by sleep. The vagal response to a meal, as indicated by PP release, is intact during sleep. The results support the importance of neural mechanisms in the modulation of the postprandial pattern of intestinal motility.

Adult↗

PubMed1997

Effects of high-fat diet and cholecystokinin receptor blockade on promotion of pancreatic ductal cell tumors in the hamster.

The mechanism by which high-fat diets potentiate pancreatic cancer is not known, but pancreaticotrophic hormones such as cholecystokinin (CCK) may be involved. The effect of CCK receptor blockade on carcinogenesis during the entire promotion period was investigated in Syrian Golden hamsters fed a high- or low-fat diet and treated with N-nitrosobis(2-oxopropyl)amine (3 x 10 mg/kg at weekly intervals). One-half of the hamsters fed a high-fat diet received the CCK-A receptor antagonist devazepide (25 nmol/kg/hr) for the duration of the experiment. At 39 weeks the incidence of pancreatic malignancies was significantly higher in hamsters fed the high-fat diet than in those fed the low-fat diet (p < 0.05). Tumor incidence was not changed by CCK receptor blockade. Potentiation of pancreatic cancer by a high-fat diet in hamsters does not appear to be influenced by endogenous CCK during the tumor promotion period.

Animals↗