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Etidronate plus calcium and vitamin D is equivalent to calcium and vitamin D alone in preventing bone mineral density loss in patients with Crohn's disease
471
differences in percent change in BMD were noted when groups were analyzed by gender, conicosteroid use or severity of baseline BMD deficit. Conclusions: Low BMD is a frequent occurrence in young patients with Crnhn's disease. Supplememation with calcium and vitamin D prevents further decline and appears to increase BMD. Adding etidronate to the regimen of calcium and vitamin D supplementation does not further enhance BMD.
Infliximab For Acute Severe Ulcerative Colitis: A Randomized Pilot Study In Non Steroid Refractory Patients Thomas Ocfisenkufin, Michael Sackmann, Burkhard Goeke Background: Steroids comprise the standard therapy for acute severe ulcerative colitis Therapeutic alternatives for patmms in whom steroids would usually be contraindicated are rare. Drugs such as cyclosporine and tacrolimus have a considerable risk of nephrotoxicity, and immunosuppressams, such as azathioprine have a delayed onset of effectivity. The chimene monoclonal antibody to tumor necrosis factor alpha, lnfliximab, seems to be effective in the treatment of steroid-refractory ulcerative colitis. We, therefore, evaluated whether Infliximab can achieve remission in non steroid refractory patients with acute severe ulcerative pancolitis in a randomized, prednisolone-controlled pilot trial over 3 months. Methods: Patients were elegible if they had acute severe disease with a modified Truelove and Wilts activity score of more than ten for at least two weeks and if they were currently not receiving immunomodulators or more than 10 mg prednisolone per day. Patients were randomly assigned to receive either infliximab or high dose predinsolone with a 50% likelyhood for each. They received either three intravenous infusions of lnfhximab at 5 rag/ kg body weight, at 0, 2 and 6 weeks (group A) or prednisolone 1.5mg/kg body weight, daily for two weeks, followed by lmg/kg for one week, followed by a tapering regimen with a weekly reduction of 5mg (group B). Therapy success was defined as clinical response in terms of a decrease of more than 5 points from baseline score and to less than 10 points total after 3 as well as after 13 weeks. Results: 13 patients (8 women, 5 men) were randomized (6 for group A and 7 for group B). The median baseline activity scores were 13.5 (12 to 18) in group A and 14.0 (11 to 18) in group B. Five of six patients in group A and six of seven patients in group B showed therapy success after three as well as after 13 weeks. One patient in group A showed no response at all and one patient in group B relapsed after eleven weeks. No significant complications or side effects were observed. Conclusion: Infliximab seems to be as effective as high dose prednisolone in the treatment of acute severe ulcerative colitis. The obtained data call for larger controlled trials.
474 Peripherally administered orexin-A and GLP-I differentially activate feedingrelated regions of the hypothalamus Fredrik Levin, Jie Ma, Qingchun Tong, Per M. Hellstrom, Annette Kirchgessner, Erik Naslund BACKGROUND: Orexin A (OXA) is a novel neuropeptide that increases food intake in rodents. Orexin immunoreactivity is displayed by neurons in the lateral hypothalamie area and enteric nervous system (Kircbgessner and Liu, '99, Naslund et al. 02) and endocnne cells in the mucosa of the upper intestine. Glucagon-like peptide-1 (GLP-1) decreases food intake in rodents and humans and is mainly found in endocrine cells in the lower intestine. Thus, OXA and GLP-1 have opposite effects on feeding behavior. The aim of this study was to determine if peripherally administered OXA and GLP-1 activate different regions of the CNS involved in the regulation of food intake. METHODS: Rats (n = 4 in each group) were given 1V saline, OXA (500 pmol/kg/min) or GLP-1 (20 pmol/kg/min) for 30 rain. Anlmah were then sacrificed and the brain removed. The experiments were repeated in rats subjected to a surgical sub-diaphragmatic bilateral vagotomy. The brain was fixed in formaldehyde and cut into 50 mm sections. Activated neurons were identified using antibodies recognizing c-fos (Chemicon International) in conjunction with confocal microscopy. RESULTS: The number of c-los positive neurons in the arcuate nucleus was 30.2 A -+ 1.7, 114.0 A i 6 9 and 25.0,8.+2.3 (Kruskal-Wallis; p<0.05) in control, OXA and GLP-1 treated rats, respectively. In the lateral hypothalamus (LH), 10.5 ,~_+1.2, 24.0 A _+ 1.1, 11.3 ~.+ 1.5 (KruskalWallis; p<0.05) c-los-positive cells were found in control, OXA and GLP-] treated rats, respectively. In the ventromedial hypothalamus (VMH), 18.7 A_+ 19, 13.5 ,~• 1.9, 49.0 A + 1.6 (Kruskal-Walhs; p<0.05) c-los-positive ceIIs were found in control, OXA and GLP1 treated rats respectively. There was no difference in the number of c-fos positive cells during OXA and GLP-1 infusion between vagotomized rats and normal rats CONCLUSION: OXA and GkP-1 differentially activate regions of the hypothalamus associated with food intake. The anatomical location of this activation is consistent with the effects of the peptides on food intake (activation of the LH with OXA and activation of the VMH with GLP-1) This effect is not mediated via the vagus nerve, but rather involves passage through the blood brain bamer or alterations in glucose homeostasis. Supported by NS27645 (AK) and the Swedish Research Council (EN).
472 A Randomized Placebo-Controlled Trial of Pegylated Interferon Alpha in Active Ulcerative Colitis Herbert Tilg, Harald Vogelsang, Othmar Ludwiczek, Herbert Lochs, Jean-Frederic Colombel, Paul Rutgeerts, Harmo Ulmer, Sandrine Kruger, Antoine Cortot, Geert D'Haens, Arthur Kaser, Marieluise Harrer, ingrid Kuhn, Walter Reinisch
Background~Aims: Uncontrolled pilot studies of interferon-alpha suggest a high remission rate in the treatment of active ulcerative colitis. The aim of this study was to evaluate safety and the role in induction of remission of pegylated interferon-alpha (PeglFN) in patients with active ulcerative colitis by a multicenter placebo-controlled trial. Methods: Patients with a CAI > 6 were randomized to receive either placebo, 0.5 ~g/kg or 1.0 g,g/kg body weight pegylated interferon-alpha once weekly (Peglntron, Schering-Plough, USA) during a twelve week treatment period. Patients receiving either mesaiazine (48/60), steroids (20/60) and/ or azathioprine (8/60) in stable dosages were included Clinical remission was defined as a CAI < 6. Results: Sixty patients entered the study (2(1 placebo, 19 in the 0.5 ~g/kg and 21 at the 10 ~tg/kg group PegIFN). The clinical remission rate at week + 12 of treatment was highest at the 0.5 p,g/kg group (11/19; 58 %), whereas remission rates were similar in placebo-treated patients (40%) and in the 1.0 ~g/kg group of PeglFN (38%). The drop-out rate altogether was 45% with the highest rate in placebo-treated (11/20, lack of efficacy) and in the 1.0 ~g/kg group (8/21, adverse events). Side effects were not observed in the 0.5 lig/kg group of PegIFN. Clinical improvement at week + 12 was accompanied by endoscopic remission in more than 60% of the patients. Conclusions: A low dose of PegIFN is safe in patients with ulcerative colitis and showed tendency towards efficacy Larger trials are needed to establish its potential role in the treatment of this disorder.
475
Localization and Function of GLP-1 Receptors in the Enteric Nervous System (ENS) Wet-Ping Chen, Jie Ma, Ricarrdo Bianchi, Annette Kirchgessner Background: Glucagon-like-peptide- 1 (GLP-1) is a hormone released from intestinal L-cells in response to luminal glucose and lipids. In addition to its role as an increrin hormone that enhances insulin release from pancreatic beta-cells, GLP-1 modulates the motility of the gut, suggestmg an effect on the enteric nervous system (ENS). The present study was undertaken: (1) to determine whether GLP-1 receptors are expressed in the ENS, and (2) to determine the effects of GLP-1 on the electrical activity of enteric neurons. Method: Total RNA was isolated with Trizol from the longuudinal muscle with adherent myenteric plexus (LMMP) or pancreatic islets (positive control) obtained from rats. RT-PCR was performed using GLP-1 receptor gene specific primers. We used the patch-clamp technique to investigate whether the electrical activity of enteric neurons is modulated by GLP-1. Results: RT-PCR detected transcripts for the GLP-1 receptor in mRNA isolated from LMMP and pancreatic islets. Recordings were made from 58 neurons in myenteric ganglia acutely isolated from the guinea pig ileum. Fifty-two percent of neurons were characterized as S-type cells (RMP, 47.6 mV) and exhibited spontaneous action potentials. Application of GLP-1 (10 nM) produced a train of action potentials in 36% of these cells, and the response was dosedependent. GLP-1 also excited AH-type myenteric neurons (RMP, -52.5 mV; n = 2 8 ) In 32.1% of these cells, GLP-1 produced a membrane depolarization associated with spike activity. Conclusions: The presence of GLP-1 receptor mRNA in enteric ganglia and excitation of both S and AH-type myenteric neurons by application of the peptide, suggests that the ENS contains functional GLP-1 receptors. The effects of GLP-1 on gastric emptying and small bowel motility are probably mediated via direct effects of the hormone on enteric neurons. Supported by NS27645.
473
Etidronate Plus Calcium and Vitamin D Is Equivalent to Calcium and Vitamin D Alone In Preventing Bone Mineral Density Loss In Patients With Crohn's Disease Jesse Siffiedeen, Tara Chalmers-Nixon, Richard N Fedorak, Kerry Siminoski, Hilary Steinhart, Gordon Greenberg Background: Patients with Crohn's disease exhibit an increased frequency of osteopenia and osteoporosis (36 to 55 percent and 5 to 57 percent, respectively). The requirements for nutrient supplementation and/or bisphosphonate therapy in this group of patients have yet to be defined. Objective: To assess the efficacy of etidronate with calcium and vitamin D supplementation compared to calcium and vitamin D supplementation alone in treating low bone mineral density (BMD) in a cohort of Crohn's disease patients. Methods: 242 patients with Crohn's disease were prospectively enrolled and BMD determined by dual energy Xray absorptiometry. At baseline 88/242 (36%) patients had normal BMD In contrast, 154/ 242 had decreased BMD, with 31 (13%) being osteoporotic; 123 (51%) being osteopenic. These 154 patients were then randomly assigned to one of the following therapeutic groups: Group A received etidronate (400 rag) for 14 days, then calcium carbonate (500 mg) plus vitamin D (400 IU) for the next 76 days. Group B received nothing for the first 14 days, then calcium carbonate (500 rag) and vitamin D (400 IU) for the next 76 days. This cycle was repeated 8 times over 24 months. Bone biochemical characteristics and percent change in BMD were assessed at 6, 12, and 24 months. Results: Mean age at baseline was 39.9 -+ 12.9 yr. Seventy-seven (50%) patients were female and 77 (50%) were male. 55.2% required corticosteroid treatment for Crohn's disease activity dunng the 24 month study. After 24 months of treatment BMD increased to an equal extent in both treatment groups The mean percent change in BMD for groups A and B was 3.80 z 5.14 vs 3.14 _+ 3.10, respectively (p =0 50) at the lumbar spine; 0.88 + 6.98 vs 134 _+ 4.45, respectively (p=0.71) at the femoral neck; 1.16 _+ 4.80 vs 1.39 -+ 4]6, respectively (p=0.83) at the total hip: and 3.54 _+ 6.16 vs 1.79 _+ 4.40, respectively (p=O.18) at the uhradistal radius. No significant
AGA Abstracts
476 GLP-1 Reduces Gastrointestinal Motility and Inhibits the Migrating Motor Complex in Healthy Subjects and IBS Patients Peter T. Schmidt, Erik Naslund, Per M. Hellstrom BACKGROUND: Glucagon-like peptide-1 (GLP-1) is released from endocrine L-cells of the distal imestine after food intake to act as an incretin hormone. In addition, GLP-1 inhibits gastric emptying and increases satiety. In rats, GLP-1 inhibits small bowel motility. The aim of the study was to examine effects of GLP-1 on gastrointestinal motility in healthy subjects and in patients with irritable bowel syndrome (IBS). METHODS: Antro-duodenal manometry was recorded by a 6-channel low-compliance water-perfused system. After a control period of 4 h, GLP-1 was given as an IV infusion for another 4 h (healthy subjects: 0.75 and 1.2 pmol/kg/min (n = 16); IBS, 1.2 and 25 pmol/kg/min (n = 14)). RESULTS:In healthy subjects, GLP-1 0.75 pmol/kg/min inhibited the migrating motor complexes (MMCs) and reduced the contraction frequency from 1.7 +/-0.2 to 1.3 +/-0.3 per min (p<0.10) and motility index from 4.9 +/-0.1 to 4.2 +/-0.3 Ln X(mmHg * s/min) (p<0.05) at the angle of Treitz: GLP-1 1.2 pmol/kg/min reduced the MMCs and contraction frequency from 2.4 +/-0.4 to
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differences in percent change in BMD were noted when groups were analyzed by gender, conicosteroid use or severity of baseline BMD deficit. Conclusions: Low BMD is a frequent occurrence in young patients with Crnhn's disease. Supplememation with calcium and vitamin D prevents further decline and appears to increase BMD. Adding etidronate to the regimen of calcium and vitamin D supplementation does not further enhance BMD.
Infliximab For Acute Severe Ulcerative Colitis: A Randomized Pilot Study In Non Steroid Refractory Patients Thomas Ocfisenkufin, Michael Sackmann, Burkhard Goeke Background: Steroids comprise the standard therapy for acute severe ulcerative colitis Therapeutic alternatives for patmms in whom steroids would usually be contraindicated are rare. Drugs such as cyclosporine and tacrolimus have a considerable risk of nephrotoxicity, and immunosuppressams, such as azathioprine have a delayed onset of effectivity. The chimene monoclonal antibody to tumor necrosis factor alpha, lnfliximab, seems to be effective in the treatment of steroid-refractory ulcerative colitis. We, therefore, evaluated whether Infliximab can achieve remission in non steroid refractory patients with acute severe ulcerative pancolitis in a randomized, prednisolone-controlled pilot trial over 3 months. Methods: Patients were elegible if they had acute severe disease with a modified Truelove and Wilts activity score of more than ten for at least two weeks and if they were currently not receiving immunomodulators or more than 10 mg prednisolone per day. Patients were randomly assigned to receive either infliximab or high dose predinsolone with a 50% likelyhood for each. They received either three intravenous infusions of lnfhximab at 5 rag/ kg body weight, at 0, 2 and 6 weeks (group A) or prednisolone 1.5mg/kg body weight, daily for two weeks, followed by lmg/kg for one week, followed by a tapering regimen with a weekly reduction of 5mg (group B). Therapy success was defined as clinical response in terms of a decrease of more than 5 points from baseline score and to less than 10 points total after 3 as well as after 13 weeks. Results: 13 patients (8 women, 5 men) were randomized (6 for group A and 7 for group B). The median baseline activity scores were 13.5 (12 to 18) in group A and 14.0 (11 to 18) in group B. Five of six patients in group A and six of seven patients in group B showed therapy success after three as well as after 13 weeks. One patient in group A showed no response at all and one patient in group B relapsed after eleven weeks. No significant complications or side effects were observed. Conclusion: Infliximab seems to be as effective as high dose prednisolone in the treatment of acute severe ulcerative colitis. The obtained data call for larger controlled trials.
474 Peripherally administered orexin-A and GLP-I differentially activate feedingrelated regions of the hypothalamus Fredrik Levin, Jie Ma, Qingchun Tong, Per M. Hellstrom, Annette Kirchgessner, Erik Naslund BACKGROUND: Orexin A (OXA) is a novel neuropeptide that increases food intake in rodents. Orexin immunoreactivity is displayed by neurons in the lateral hypothalamie area and enteric nervous system (Kircbgessner and Liu, '99, Naslund et al. 02) and endocnne cells in the mucosa of the upper intestine. Glucagon-like peptide-1 (GLP-1) decreases food intake in rodents and humans and is mainly found in endocrine cells in the lower intestine. Thus, OXA and GLP-1 have opposite effects on feeding behavior. The aim of this study was to determine if peripherally administered OXA and GLP-1 activate different regions of the CNS involved in the regulation of food intake. METHODS: Rats (n = 4 in each group) were given 1V saline, OXA (500 pmol/kg/min) or GLP-1 (20 pmol/kg/min) for 30 rain. Anlmah were then sacrificed and the brain removed. The experiments were repeated in rats subjected to a surgical sub-diaphragmatic bilateral vagotomy. The brain was fixed in formaldehyde and cut into 50 mm sections. Activated neurons were identified using antibodies recognizing c-fos (Chemicon International) in conjunction with confocal microscopy. RESULTS: The number of c-los positive neurons in the arcuate nucleus was 30.2 A -+ 1.7, 114.0 A i 6 9 and 25.0,8.+2.3 (Kruskal-Wallis; p<0.05) in control, OXA and GLP-1 treated rats, respectively. In the lateral hypothalamus (LH), 10.5 ,~_+1.2, 24.0 A _+ 1.1, 11.3 ~.+ 1.5 (KruskalWallis; p<0.05) c-los-positive cells were found in control, OXA and GLP-] treated rats, respectively. In the ventromedial hypothalamus (VMH), 18.7 A_+ 19, 13.5 ,~• 1.9, 49.0 A + 1.6 (Kruskal-Walhs; p<0.05) c-los-positive ceIIs were found in control, OXA and GLP1 treated rats respectively. There was no difference in the number of c-fos positive cells during OXA and GLP-1 infusion between vagotomized rats and normal rats CONCLUSION: OXA and GkP-1 differentially activate regions of the hypothalamus associated with food intake. The anatomical location of this activation is consistent with the effects of the peptides on food intake (activation of the LH with OXA and activation of the VMH with GLP-1) This effect is not mediated via the vagus nerve, but rather involves passage through the blood brain bamer or alterations in glucose homeostasis. Supported by NS27645 (AK) and the Swedish Research Council (EN).
472 A Randomized Placebo-Controlled Trial of Pegylated Interferon Alpha in Active Ulcerative Colitis Herbert Tilg, Harald Vogelsang, Othmar Ludwiczek, Herbert Lochs, Jean-Frederic Colombel, Paul Rutgeerts, Harmo Ulmer, Sandrine Kruger, Antoine Cortot, Geert D'Haens, Arthur Kaser, Marieluise Harrer, ingrid Kuhn, Walter Reinisch
Background~Aims: Uncontrolled pilot studies of interferon-alpha suggest a high remission rate in the treatment of active ulcerative colitis. The aim of this study was to evaluate safety and the role in induction of remission of pegylated interferon-alpha (PeglFN) in patients with active ulcerative colitis by a multicenter placebo-controlled trial. Methods: Patients with a CAI > 6 were randomized to receive either placebo, 0.5 ~g/kg or 1.0 g,g/kg body weight pegylated interferon-alpha once weekly (Peglntron, Schering-Plough, USA) during a twelve week treatment period. Patients receiving either mesaiazine (48/60), steroids (20/60) and/ or azathioprine (8/60) in stable dosages were included Clinical remission was defined as a CAI < 6. Results: Sixty patients entered the study (2(1 placebo, 19 in the 0.5 ~g/kg and 21 at the 10 ~tg/kg group PegIFN). The clinical remission rate at week + 12 of treatment was highest at the 0.5 p,g/kg group (11/19; 58 %), whereas remission rates were similar in placebo-treated patients (40%) and in the 1.0 ~g/kg group of PeglFN (38%). The drop-out rate altogether was 45% with the highest rate in placebo-treated (11/20, lack of efficacy) and in the 1.0 ~g/kg group (8/21, adverse events). Side effects were not observed in the 0.5 lig/kg group of PegIFN. Clinical improvement at week + 12 was accompanied by endoscopic remission in more than 60% of the patients. Conclusions: A low dose of PegIFN is safe in patients with ulcerative colitis and showed tendency towards efficacy Larger trials are needed to establish its potential role in the treatment of this disorder.
475
Localization and Function of GLP-1 Receptors in the Enteric Nervous System (ENS) Wet-Ping Chen, Jie Ma, Ricarrdo Bianchi, Annette Kirchgessner Background: Glucagon-like-peptide- 1 (GLP-1) is a hormone released from intestinal L-cells in response to luminal glucose and lipids. In addition to its role as an increrin hormone that enhances insulin release from pancreatic beta-cells, GLP-1 modulates the motility of the gut, suggestmg an effect on the enteric nervous system (ENS). The present study was undertaken: (1) to determine whether GLP-1 receptors are expressed in the ENS, and (2) to determine the effects of GLP-1 on the electrical activity of enteric neurons. Method: Total RNA was isolated with Trizol from the longuudinal muscle with adherent myenteric plexus (LMMP) or pancreatic islets (positive control) obtained from rats. RT-PCR was performed using GLP-1 receptor gene specific primers. We used the patch-clamp technique to investigate whether the electrical activity of enteric neurons is modulated by GLP-1. Results: RT-PCR detected transcripts for the GLP-1 receptor in mRNA isolated from LMMP and pancreatic islets. Recordings were made from 58 neurons in myenteric ganglia acutely isolated from the guinea pig ileum. Fifty-two percent of neurons were characterized as S-type cells (RMP, 47.6 mV) and exhibited spontaneous action potentials. Application of GLP-1 (10 nM) produced a train of action potentials in 36% of these cells, and the response was dosedependent. GLP-1 also excited AH-type myenteric neurons (RMP, -52.5 mV; n = 2 8 ) In 32.1% of these cells, GLP-1 produced a membrane depolarization associated with spike activity. Conclusions: The presence of GLP-1 receptor mRNA in enteric ganglia and excitation of both S and AH-type myenteric neurons by application of the peptide, suggests that the ENS contains functional GLP-1 receptors. The effects of GLP-1 on gastric emptying and small bowel motility are probably mediated via direct effects of the hormone on enteric neurons. Supported by NS27645.
473
Etidronate Plus Calcium and Vitamin D Is Equivalent to Calcium and Vitamin D Alone In Preventing Bone Mineral Density Loss In Patients With Crohn's Disease Jesse Siffiedeen, Tara Chalmers-Nixon, Richard N Fedorak, Kerry Siminoski, Hilary Steinhart, Gordon Greenberg Background: Patients with Crohn's disease exhibit an increased frequency of osteopenia and osteoporosis (36 to 55 percent and 5 to 57 percent, respectively). The requirements for nutrient supplementation and/or bisphosphonate therapy in this group of patients have yet to be defined. Objective: To assess the efficacy of etidronate with calcium and vitamin D supplementation compared to calcium and vitamin D supplementation alone in treating low bone mineral density (BMD) in a cohort of Crohn's disease patients. Methods: 242 patients with Crohn's disease were prospectively enrolled and BMD determined by dual energy Xray absorptiometry. At baseline 88/242 (36%) patients had normal BMD In contrast, 154/ 242 had decreased BMD, with 31 (13%) being osteoporotic; 123 (51%) being osteopenic. These 154 patients were then randomly assigned to one of the following therapeutic groups: Group A received etidronate (400 rag) for 14 days, then calcium carbonate (500 mg) plus vitamin D (400 IU) for the next 76 days. Group B received nothing for the first 14 days, then calcium carbonate (500 rag) and vitamin D (400 IU) for the next 76 days. This cycle was repeated 8 times over 24 months. Bone biochemical characteristics and percent change in BMD were assessed at 6, 12, and 24 months. Results: Mean age at baseline was 39.9 -+ 12.9 yr. Seventy-seven (50%) patients were female and 77 (50%) were male. 55.2% required corticosteroid treatment for Crohn's disease activity dunng the 24 month study. After 24 months of treatment BMD increased to an equal extent in both treatment groups The mean percent change in BMD for groups A and B was 3.80 z 5.14 vs 3.14 _+ 3.10, respectively (p =0 50) at the lumbar spine; 0.88 + 6.98 vs 134 _+ 4.45, respectively (p=0.71) at the femoral neck; 1.16 _+ 4.80 vs 1.39 -+ 4]6, respectively (p=0.83) at the total hip: and 3.54 _+ 6.16 vs 1.79 _+ 4.40, respectively (p=O.18) at the uhradistal radius. No significant
AGA Abstracts
476 GLP-1 Reduces Gastrointestinal Motility and Inhibits the Migrating Motor Complex in Healthy Subjects and IBS Patients Peter T. Schmidt, Erik Naslund, Per M. Hellstrom BACKGROUND: Glucagon-like peptide-1 (GLP-1) is released from endocrine L-cells of the distal imestine after food intake to act as an incretin hormone. In addition, GLP-1 inhibits gastric emptying and increases satiety. In rats, GLP-1 inhibits small bowel motility. The aim of the study was to examine effects of GLP-1 on gastrointestinal motility in healthy subjects and in patients with irritable bowel syndrome (IBS). METHODS: Antro-duodenal manometry was recorded by a 6-channel low-compliance water-perfused system. After a control period of 4 h, GLP-1 was given as an IV infusion for another 4 h (healthy subjects: 0.75 and 1.2 pmol/kg/min (n = 16); IBS, 1.2 and 25 pmol/kg/min (n = 14)). RESULTS:In healthy subjects, GLP-1 0.75 pmol/kg/min inhibited the migrating motor complexes (MMCs) and reduced the contraction frequency from 1.7 +/-0.2 to 1.3 +/-0.3 per min (p<0.10) and motility index from 4.9 +/-0.1 to 4.2 +/-0.3 Ln X(mmHg * s/min) (p<0.05) at the angle of Treitz: GLP-1 1.2 pmol/kg/min reduced the MMCs and contraction frequency from 2.4 +/-0.4 to
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