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Biomedical subjects

A Wettergren

Publications and source records attributed to A Wettergren.

At least 19 recordsLinked to original sources
PubMed2004

Glucagon-like peptide-2 inhibits antral emptying in man, but is not as potent as glucagon-like peptide-1.

BACKGROUND: GLP-1 (glucagon-like peptide-1) and GLP-2 (glucagon-like peptide-2) are released in equimolar amounts in response to meal ingestion. GLP-1 inhibits gastric emptying and reduces postprandial gastric and exocrine pancreatic secretion and may play a physiological regulatory role in controlling appetite and energy intake in humans. The role of GLP-2 is more uncertain. Based on the results of animal studies, it has been suggested that GLP-2 may induce intestinal epithelial growth and inhibit gastric motility. The aim of this study was to determine to what extent GLP-2 alone or together with GLP-1 inhibits gastric emptying and the sensation of hunger in man. METHODS: Eight healthy volunteers were tested in a double-blind, placebo-controlled fashion. Antral emptying of a liquid meal and hunger ratings were determined using ultrasound technology and visual analogue scales scoring during infusions of saline, GLP-2 (0.5, and 1.0 pmol kg body wt(-1) min(-1)), GLP-1 (0.5 pmol kg body wt(-1) min(-1)) or GLP-1 and GLP-2 (0.5 pmol kg body wt(-1) min(-1)). RESULTS: The GLP-2 infusions resulted in a dose-dependent increase in antral emptying time (35%; ns and 75%; P = 0.049) compared to saline, but GLP-2 was less potent than GLP-1, which increased the antral emptying time by 192% (P < 0.001). Addition of GLP-2 to the GLP-1 infusion did not alter the antral emptying time compared with GLP-1 alone. The GLP-1 infusion decreased the sensation of hunger compared with saline (P = 0.023), whereas the two GLP-2 infusions had no significant effect. Addition of GLP-2 to the GLP-1 infusion did not decrease the sensation of hunger further. CONCLUSIONS: Both GLP-1 and GLP-2 inhibit antral emptying in man, but GLP-1 is more potent.

Adult↗
PubMed1999

Inhibition of sham feeding-stimulated human gastric acid secretion by glucagon-like peptide-2.

Glucagon-like peptide (GLP)-2 is formed from proglucagon in the intestinal L cells and is secreted postprandially in parallel with the insulinotropic hormone GLP-1, the latter of which, in addition, acts to inhibit gastric secretion and motility by inhibiting central parasympathetic outflow. We now studied the effect of GLP-2 on gastric secretion stimulated by sham feeding to test the hypothesis that also GLP-2 acts as an enterogastrone. Eight healthy volunteers were studied twice on separate days. They were sham fed with and without GLP-2 infused iv at a rate of 0.8 pmol/kg x min. Gastric contents were aspirated continuously by a nasogastric tube for determination of acid secretion, volume, and osmolarity. Sham feeding increased gastric acid secretion nearly 5-fold. Infusion of GLP-2 reduced incremental acid secretion by 65+/-6%, compared with saline infusion (delta8.75+/-0.37 vs. delta3.04+/-0.47 mmol x 60 min; P<0.01). Plasma concentrations of GLP-2 rose from a basal mean of 3.3+/-0.9 to a mean of 115+/-8 pmol/L (range, 57-149 pmol/L) during infusion of GLP-2 and remained at basal level during saline infusion. Plasma concentrations of GLP-1, gastrin, cholecystokinin, and secretin remained low and unchanged on both study days. We conclude that GLP-2 is a powerful inhibitor of gastric acid secretion in man. Further investigations will show to what extent GLP-2 contributes to the inhibitory effects on gastric secretion exerted by hormones from the distal small intestine, under physiological circumstances.

Cholecystokinin↗
PubMed1998

Amidated and non-amidated glucagon-like peptide-1 (GLP-1): non-pancreatic effects (cephalic phase acid secretion) and stability in plasma in humans.

The incretin and enterogastrone hormone, GLP-1, occurs in an amidated (GLP-1 (7-36) amide; 75%) and a glycine-extended (GLP-1 (7-37); 25%) form. Their effects on the endocrine pancreas are similar and their overall (mainly renal) elimination rates appear to equal. Assuming that they might differentially affect non-pancreatic targets we investigated the effect of GLP-1 (7-37) infused at 0.7 pmol/kg/min on sham-feeding induced acid secretion in six healthy volunteers. The infusion increased the plasma concentrations from 16+/-2 pmol/l to 45+/-2 pmol/l. This was associated with a 61+/-14% decrease in acid output compared to saline and was not significantly different from that previously observed with GLP-1 (7-36) amide infused at the same rate. We then compared the degradation of the two forms in human plasma at 37 degrees C in vitro. T1/2 values were 32+/-3 (7-37) and 42+/-2 min (7-36) amide (P=0.007). The difference in metabolism persisted after addition of diprotin A, an inhibitor of dipeptidyl peptidase IV, the enzyme responsible for the initial degradation of GLP-1 in plasma, and broader enzyme inhibitors. Thus, the only effect of the amidation of GLP-1 seems to be to enhance its survival in plasma.

Adult↗
PubMed1998

The inhibitory effect of glucagon-like peptide-1 (7-36)amide on antral motility is antagonized by its N-terminally truncated primary metabolite GLP-1 (9-36)amide.

In plasma, glucagon-like peptide-1 7-36 amide (GLP-1) is rapidly degraded from the N terminus, generating the endogenous metabolite GLP-1 9-36 amide. This cleavage of GLP-1 eliminates its incretin effect, and the metabolite even may act as an antagonist. We have shown previously that GLP-1 strongly inhibited cephalic-induced antral motility in pigs. We decided, therefore, to examine the effect of GLP-1 9-36 amide, with and without GLP-1, on cephalic-induced motility in pigs. In one series of experiments, we studied the effect of three different doses of GLP-1 9-36 amide (2, 4, and 10 pmol/kg/min) on insulin-induced (hypoglycemia) antral motility in anaesthetized pigs (n = 9). In another series, we studied the effect of infusion of GLP-1 9-36 amide in two different doses (1 and 5 pmol/kg/min) in six pigs in which the antral motility was inhibited by GLP-1 7-36 amide in a dose of 2 pmol/kg/min. Plasma levels of intact GLP-1 7-36 amide and GLP-1 9-36 amide were determined using specific radioimmunoassays. Insulin-induced hypoglycemia increased the antral motility index from 0.4 +/- 0.1 to 8.3 +/- 3.5 (cm/min). The motility was constant throughout the experimental period and was absolutely unaffected by the infusion of GLP-1 9-36 amide at 10 pmol/kg/min, which resulted in a plasma concentration of 351 +/- 60 pmol/l. The inhibitory effect of GLP-1 7-36 amide on antral motility was reduced from 93 +/- 3% to 33 +/- 9% (p < 0.05) by concomitant infusion of GLP-1 9-36 amide in a dose of 5 pmol/kg/min. The metabolite GLP-1 9-36 amide has no effect on antral motility in pigs but is able to antagonize the inhibitory effect of GLP-1. Thus, an intact N terminus is essential for the gastrointestinal actions of GLP-1. Its primary metabolite may act as an endogenous antagonist.

Animals↗
PubMed1998

Inhibition of human gastric lipase secretion by glucagon-like peptide-1.

Glucagon-like peptide-1 (GLP-1) may be one of the enterogastrone hormones of the ileal brake mechanism. We therefore studied its effects on gastric lipase secretion in healthy volunteers and vagotomized patients during infusion of pentagastrin. The intestinal incretin hormone GLP-1 (glucagon-like peptide-1, 7-36 amide) was investigated because of its inhibitory effects on gastric acid secretion and motility. GLP-1 infused intravenously in amounts corresponding to the postprandial release significantly inhibited pentagastrin-stimulated gastric lipase secretion and lipolytic activity. The inhibitory effect of GLP-1 persisted in vagotomized patients, suggesting that fundic chief cells, from which gastric lipase is released, or neighboring inhibitory cells could be equipped with GLP-1 receptors. Vagotomized patients had significantly higher plasma concentrations of gastrin and secretin. No significant changes of gastrin, secretin, and CCK secretion were seen during GLP-1 infusion in the vagotomized patients, whereas secretin decreased significantly in the healthy volunteers. GLP-1 seems to be a naturally occurring inhibitor of gastric lipase secretion acting via a nonvagal mechanism. Our results indicate that gastric lipase secretion is subject to hormonal stimulatory as well as inhibitory mechanisms.

Aged↗
PubMed1998

Glucagon-like peptide-2 inhibits centrally induced antral motility in pigs.

BACKGROUND: Glucagon-like peptide-2 is formed from proglucagon in the intestinal L-cells and is secreted postprandially in parallel with the insulinotropic hormone GLP-1 (glucagon-like peptide-1), which in addition acts to inhibit gastric motility (enterogastrone effect) by inhibiting central parasympathetic outflow. GLP-2 has no effect on the endocrine pancreas. We here tested the hypothesis that GLP-2 acts as an enterogastrone. METHODS: Fourteen anesthetized pigs with their splanchnic nerves cut were subjected to insulin hypoglycemia, and force transducers were sutured to the antrum to record motility. GLP-2 was infused intravenously in doses from 1 to 6 pmol/kg/min after the onset of antral motility in response to hypoglycemia. RESULTS: Insulin hypoglycemia invariably and greatly increased the frequency and amplitude of antral phasic contractions. Infusions of GLP-2 dose dependently (1-6 pmol/kg/min) inhibited antral motility. At 2 pmol/kg/min, resulting in plasma GLP-2 concentrations of 102.5+/-19 pmol/l (normal postprandial range, 30-82 pmol/l), the motility index was inhibited by 91%+/-14%. CONCLUSIONS: Both of the intestinal glucagon-like peptides may operate as hormonal transmitters of the ileal brake effect.

Animals↗
PubMed1998

Glucagon-like peptide-1 inhibits gastropancreatic function by inhibiting central parasympathetic outflow.

Glucagon-like peptide (GLP)-1 inhibits acid secretion and gastric emptying in humans, but the effect on acid secretion is lost after vagotomy. To elucidate the mechanism involved, we studied its effect on vagally stimulated gastropancreatic secretion and motility in urethan-anesthetized pigs with cut splanchnic nerves, in which insulin-induced hypoglycemia elicited a marked stimulation of gastropancreatic secretion and antral motility. In addition, we studied vagally stimulated motility and pancreatic secretion in isolated perfused preparations of the porcine antrum and pancreas. GLP-1 infusion (2 pmol. kg-1. min-1) strongly and significantly inhibited hypoglycemia-induced antral motility, gastric acid secretion, pancreatic bicarbonate and protein secretion, and pancreatic polypeptide (PP) secretion. GLP-1 (at 10(-10)-10(-8) mol/l) did not inhibit vagally induced antral motility, pancreatic exocrine secretion, or gastrin and PP secretion in isolated perfused antrum and pancreas. We conclude that the inhibitory effect of peripheral GLP-1 on upper gastrointestinal secretion and motility is exerted via interaction with centers in the brain or afferent neural pathways relaying to the vagal motor nuclei.

Animals↗
PubMed1997

The inhibitory effect of glucagon-like peptide-1 (GLP-1) 7-36 amide on gastric acid secretion in humans depends on an intact vagal innervation.

BACKGROUND: Glucagon-like peptide-1 (GLP-1)(7-36) amide is an intestinal incretin hormone which also inhibits gastric acid secretion in humans. Its mechanism of action is unclear, but it strongly inhibits vagally induced secretion (sham feeding), suggesting that it could influence vagal activity. AIM/METHODS: The effect of intravenous GLP-1 (7-36 amide) (1 pmol/kg/min) was studied on pentagastrin induced acid secretion in otherwise healthy subjects, previously vagotomised for duodenal ulcer (n = 8) and in a group of young (n = 8) and old (n = 6) healthy volunteers. RESULTS: Pentagastrin increased acid secretion significantly in all three groups, but the plateau concentration in the vagotomised subjects was lower than in controls. Infusion of GLP-1 (7-36 amide) significantly inhibited acid secretion in the control groups (to 67 (SEM 6) and 74 (SEM 3)% of plateau concentrations in young and old controls, respectively) but had no effect in the vagotomised subjects. Differences in plasma concentrations of GLP-1 (7-36 amide), recovery of gastric marker, duodenal regurgitation, or Helicobacter pylori status could not explain the lack of effect. Blood glucose was lowered equally by GLP-1 (7-36 amide) in all subjects. CONCLUSION: The inhibitory effect of GLP-1 (7-36 amide) on acid secretion depends on intact vagal innervation of the stomach.

Adult↗
PubMed1997

Glucagon-like peptide-1 7-36 amide and peptide YY have additive inhibitory effect on gastric acid secretion in man.

BACKGROUND: Glucagon-like peptide-1 7-36 amide (GLP-1) and peptide YY (PYY) are colocalized in the L-cell of the ileal mucosa, and both peptides may function as enterogastrone hormones. However, it is not known whether they interact with regard to the effect on acid secretion. METHODS: The effect of intravenous infusion of GLP-1 and PYY, either alone or in combination, on pentagastrin-induced acid secretion in eight healthy volunteers was examined. The peptides were infused at two different rates: 0.25 pmol/kg/min (low rate) and 0.5 pmol/kg/min (high rate). RESULTS: Given alone, GLP-1 and PYY inhibited acid secretion by 26 +/- 5% and 18 +/- 5% (low rate) and 45 +/- 8% and 38 +/- 7% (high rate), respectively. Combined infusion resulted in an inhibition of 32 +/- 5% (low rate) and 62 +/- 7% (high rate). Both infusion rates resulted in GLP-1 and PYY plasma concentrations below or similar to postprandial levels. CONCLUSION: The present study suggests that the interaction between GLP-1 and PYY in man is of the additive type. The results indicate that GLP-1 and PYY have an important role in the physiologic control of gastric acid secretion.

Adult↗
PubMed1996

Secretion of the incretin hormones glucagon-like peptide-1 and gastric inhibitory polypeptide correlates with insulin secretion in normal man throughout the day.

BACKGROUND: The insulinotropic hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), secreted from the K-cells of the upper small intestine and from the L-cells of the lower small intestine, respectively, are thought to be responsible for intestinal stimulation of insulin secretion. If true, their plasma concentrations should parallel the meal-related diurnal changes in plasma insulin concentrations. METHODS: Using COOH-terminal assays, thought to reflect accurately their rates of secretion, we measured circulating levels of GIP and GLP-1 in six normal subjects for 15 h of a day, during which they ate three mixed meals. RESULTS: Both GIP and GLP-1 concentrations increased significantly and in parallel with insulin in response to all three meals. The plasma insulin concentrations correlated significantly with both GIP and GLP-1 values throughout the study period (correlation coefficients, 0.49 +/- 0.07 and 0.56 +/- 0.05; p < 0.001). CONCLUSIONS: These results support the notion that GLP-1 and GIP are important incretin hormones.

Adult↗
PubMed1995

Closure of rectal stump after colectomy for acute colitis.

In a retrospective study complications, mortality and morbidity following acute colectomy for severe colitis with intra-abdominal closure of the rectal stump were reviewed in 147 consecutive patients (71 women and 76 men, median age of 40 years, range 18-95 years). Five patients (3%) died within 30 days postoperatively; none of the deaths were related to the rectal stump. Three patients (2%) had a pelvic abscess due to leakage of the rectal closure, all were treated successfully with percutaneous drainage, guided by ultrasonography. No difficulties in locating the rectal stump or performing intended subsequent surgery were reported. The overall complications and mortality rate in this study are low and comparable to the best results reported from centers using the mucous fistula. Closure of the rectal stump is a safe procedure, and has the advantage of not leaving the patient with a second stoma.

Acute Disease↗
PubMed1995

Social and sexual function following ileal pouch-anal anastomosis.

PURPOSE: Patients who undergo surgery for ulcerative colitis are usually young and active. When surgery becomes necessary, their future social and sexual function is of major concern. This study was performed to be able to give more detailed information of what is to be expected. METHODS: Forty-nine consecutive patients (26 men and 23 women) who underwent ileal J-pouch-anal anastomosis for ulcerative colitis between November 1983 and September 1986 in the authors' institution were personally interviewed regarding details of their preoperative and postoperative social and sexual functions. RESULTS: Eighty-eight percent had reduced capacity to work preoperatively compared with 6 percent postoperatively. Thirty-one percent resumed work in the period with diverting ileostomy. Leisure time activities were reduced in 47 percent preoperatively, whereas 6 percent had limitations postoperatively. In 35 percent of women, frequency of intercourse was increased postoperatively, and none reported a decreased frequency. None of the women who were able to achieve orgasm preoperatively reported a postoperative disturbance of this ability, and 16 percent experienced an increased quality of orgasm. Postoperatively none reported dyspareunia, vaginal discharge, or changes in their menstrual cycle. Frequency of intercourse and ability to achieve orgasm remained unchanged for the majority of men; however, one developed erectile dysfunction, and one complained of retrograde ejaculation. Sexual activity in men was less affected by the presence of an ileostomy, and 69 percent had intercourse in the period with ileostomy compared with 30 percent of women. None of the patients complained of anal pain, soiling, or fecal leakage during intercourse, but one women reported some discomfort from the pouch during intercourse. None of the patients wanted to return to a life with an ileostomy. CONCLUSION: The social and sexual function, quality of life, after ileal J-pouch anastomosis is improved when compared with the period with ulcerative colitis and the time with diverting ileostomy. In men, however, a frequency of sexual dysfunction similar to what is seen after proctectomy for benign diseases should be underlined.

Adolescent↗
PubMed1994

[Radiological findings in patients with a J-shaped ileal reservoir].

This study comprised 116 patients with either ulcerative colitis or familial adenomatous polyposis, who were treated from 1983 to 1990. The patients were subjected to total colectomy followed by formation of an ileoanal reservoir (J-pouch). In a retrospective study the radiological findings of the J-pouch and the reservoir related complications are presented and a description of the applied technique for pouchography is given. A total of 513 radiological investigations were performed--median two per patient (range: 1-44). All 116 patients were subjected to pouchography while 59 patients additionally underwent conventional X-ray investigations, 42 patients were referred to ultrasound and ten patients to CT. Fourty-five percent of the patients presented no radiological complications at all. Patients with a normal primary pouchogram showed a significantly lower risk of long term complications related to the pouch. Pouchography was a useful method for excluding pouch pathology before restoring intestinal continuity as well as showing fistulas or cavities. In cases of leakage and especially stenosis and pouchitis pouchography was, however, less reliable. Ultrasound examination combined with CT-scan was beneficial in diagnosing abscesses.

Adenomatous Polyposis Coli↗
PubMed1994

Tissue and plasma concentrations of amidated and glycine-extended glucagon-like peptide I in humans.

Using specific radioimmunoassays, we studied the occurrence of amidated and glycine-extended glucagon-like peptide I (GLP-I) molecules in the human small intestine and pancreas and in the circulation system in response to a breakfast meal. Through gel permeation chromatography of extracts of the human pancreas (n = 5), we found that 71% of the GLP-I immunoreactivity eluted as a large molecule corresponding to the major proglucagon fragment, 24% corresponded to GLP-I 1-36 amide, and 5% to GLP-I 1-37. By gel permeation chromatography of extracts of human small intestine (n = 6), we found that all immunoreactivity eluted in one peak at the common elution position of the two insulin-releasing peptides, GLP-I 7-36 amide and GLP-I 7-37. Of the GLP-I immunoreactivity, 80% corresponded to GLP-I 7-36 amide and 20% to GLP-I 7-37. The mean concentrations of amidated GLP-I and glycine-extended GLP-I in fasting plasma were 7 +/- 1 and 6 +/- 1 pM, respectively (n = 6). In response to a breakfast meal, the concentration of amidated GLP-I rose significantly amounting to 41 +/- 5 pM 90 min after the meal ingestion, whereas the concentration of glycine-extended GLP-I only rose slightly to a maximum of 10 +/- 1 pM. Thus, both amidated and glycine-extended GLP-I molecules are produced in the small intestine and in the pancreas in humans. Both amidated and glycine-extended GLP-I are measurable in fasting plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Glucagon-like peptide-1 7-36 amide and peptide YY from the L-cell of the ileal mucosa are potent inhibitors of vagally induced gastric acid secretion in man.

BACKGROUND: Glucagon-like peptide (GLP-1) 7-36 amide and peptide YY (PYY) from the L-cell of the ileal mucosa are potent inhibitors of gastric acid secretion in man. It is not clear, however, by which mechanism(s) they inhibit acid secretion. In dogs the inhibitory effect of PYY on acid secretion may be mediated mainly through neural pathways. The mechanism of action of GLP-1 might be similar. The aim of the present study was to examine the effects of GLP-1 might be similar. The aim of the present study was to examine the effects of GLP-1 and PYY on the vagally induced gastric acid secretion in man. METHODS: A modified sham feeding technique, chew and spit, was used. Six healthy volunteers were randomly assigned to receive intravenous infusion of saline, GLP-1 (41 pmol/kg/h), or peptide YY (50 pmol/kg/h). RESULTS: The infusion of GLP-1 and PYY resulted in plasma concentrations of 60 +/- 9 pmol/l and 84 +/- 11 pmol/l, respectively. GLP-1 and PYY both significantly inhibited the intergrated acid output by 67 +/- 6% and 68 +/- 9%, respectively, compared with the integrated outputs in a control experiment with saline infusion. Serum gastrin and plasma somatostatin concentrations remained unchanged during saline, GLP-1, and PYY infusions. CONCLUSIONS: GLP-1 and PYY are both potent inhibitors of the cephalic phase of acid secretion, indicating that at least part of the inhibitory effect of GLP-1 and PYY in man is mediated through neural pathways. Furthermore, the inhibitory effect seems to be independent of circulating concentrations of gastrin and somatostatin.

Adult↗
PubMed1994

Evaluation of 18 cases of conservative proctectomy with low transsection of the anorectum for benign diseases.

OBJECTIVE: To present our experience of conservative proctectomy in the treatment of patients with benign diseases of the rectum. DESIGN: Retrospective study. SETTING: University hospital. SUBJECTS: 18 patients with benign diseases of the rectum for whom a pouch was unsuitable. INTERVENTIONS: Conservative proctectomy with transsection of the anorectum. MAIN OUTCOME MEASURES: Mortality and morbidity. RESULTS: In 10 patients the wounds healed primarily. The remaining 8 developed presacral abscesses, which drained either spontaneously or after a drainage operation. At the end of the 19 month follow up period four still had presacral cavities with fistulas to the anal canal, and one patient had died of a cause unrelated to the operation. No patient complained of sexual dysfunction. CONCLUSION: If proctectomy is indicated for a benign disease a limited excision with transsection of the anorectum at the pectinate line is safe if the closed anal canal is examined carefully and residual mucosa removed. It should not be used for patients with severe inflammatory or fibrous changes in the perirectal tissue.

Adult↗
PubMed1993

[Pouchitis: acute inflammation in the pelvic ileal reservoir. Diagnostic criteria, frequency, possible etiological factors and treatment].

Pouchitis is a significant long-term complication of restorative proctocolectomy. Pouchitis is characterized by diarrhoea, fever, malaise, abdominal pain and in few a patients a worsening of already present extraintestinal manifestations may occur. The estimated probability of pouchitis occurring within five years is approximately 35%. Standard diagnostic criteria have not yet been established, but clinical symptoms, endoscopic and histological features should be included. The cause of pouchitis is unknown, bacterial over-growth, faecal stasis, oxygen free radicals, secondary and deconjugated bile acids, shortchain fatty acids, gastrointestinal hormones and an immunologically-mediated reaction have all been suggested as possible etiological factors. Metronidazole is the most commonly used treatment and has prompt effect in more than 90% of the patients. Steroids and 5-aminosalicylic acid derivatives also seem to be effective. A diverting ileostomy is necessary in only five to seven percent of the patients, and in less than one percent does pouchitis result in excision of the pouch. Controlled trials with uniform diagnostic criteria are required to assess the effectiveness of the individual regimens.

Acute Disease↗