motilin and Diabetes-Mellitus--Type-1

Here we have investigated the pharmacokinetics, pharmacodynamics and safety of single doses of camicinal in type 1 diabetes mellitus (T1DM) patients with a history of slow gastric emptying with symptoms consistent with gastroparesis.. In a randomized, double-blind, placebo-controlled, incomplete block, three-period, two-centre crossover study, patients received oral administration of placebo and two of the three possible doses of camicinal (25, 50 or 125 mg). Gastric emptying ((13) C-octanoic acid breath test), pharmacokinetics and safety were primary outcomes.. Nine of the 10 patients enrolled completed the study. Gastric half-emptying time decreased by -95 min (95% CI: -156.8, -34.2) after a single dose of camicinal 125 mg compared with placebo (52 vs. 147 min, P < 0.05), representing a 65% improvement. A decrease of the gastric half-emptying time compared with placebo (approximately 39 min) was observed with camicinal 25 and 50 mg, representing a 27% reduction for both doses (not statistically significant). A positive exposure-response relationship was demonstrated across all doses. The effects of camicinal on gastric half-emptying time were not influenced by fasting glucose levels. Single doses up to 125 mg were well tolerated. Camicinal was well absorbed, exhibiting linear and approximately dose-proportional pharmacokinetic characteristics and a clear exposure-response relationship with gastric emptying.. Camicinal significantly accelerated gastric emptying of solids in T1DM patients following administration of a single oral dose. Camicinal was well tolerated and exhibited similar pharmacokinetic characteristics in diabetic patients to those previously reported in healthy volunteers.

Topics: Adolescent; Adult; Aged; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Double-Blind Method; Gastric Emptying; Gastrointestinal Agents; Humans; Middle Aged; Motilin; Piperazines; Piperidines; Young Adult

To observe the effect of Jianpi Wenshen Decoction (JWD) on serum gastrin, plasma motilin and somatostatin in patients of diabetic diarrhea (DD).. Patients with DD were randomly divided into two groups, the JWD group and the control group treated with Loperamide (LPA). Besides, a normal control group was set up. Changes of serum gastrin, plasma motilin and somatostatin were observed.. Before treatment, the levels of gastrin and motilin in both groups were higher and somatostatin lower than those in the normal control group. After 1 month treatment, levels of the three indices were restored in both group approaching the normal range with insignificance as compared with those in the normal control group (P > 0.05). Level of plasma motilin and serum gastrin showed an increasing trend along with the therapeutic effect elevation, while level of somatostatin showed a decreasing trend.. JWD could promote the recovery of the impaired function of vegetative nerve system in DD patients. At the same time, serum gastrin, plasma motilin and somatostatin may be taken as the indexes for evaluating the efficacy in treating DD.

Topics: Adult; Aged; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diarrhea; Drugs, Chinese Herbal; Female; Gastrins; Humans; Male; Middle Aged; Motilin; Phytotherapy; Somatostatin

Erythromycin, a motilin agonist, is a potent prokinetic. ABT-229 is a specific motilin agonist that dose dependently accelerates gastric emptying. Dyspepsia and gastroparesis are common problems in type 1 diabetes mellitus. We aimed to evaluate the efficacy of ABT-229 in symptomatic diabetic patients with and without delayed gastric emptying.. Patients with type 1 diabetes and postprandial symptoms were randomised (n=270). Based on a validated C(13) octanoic acid breath test, patients were assigned to either the delayed or normal gastric emptying strata. Patients received one of four doses of ABT-229 (1.25, 2.5, 5, or 10 mg twice daily before breakfast and dinner) or placebo for four weeks following a two week baseline. A self report questionnaire measured symptoms on visual analogue scales; the primary outcome was assessment of change in the total upper abdominal symptom severity score (range 0-800 mm) from baseline to the final visit.. The treatment arms were similar regarding baseline characteristics. There was symptom improvement on placebo and a similar level of improvement on active therapy for the upper abdominal discomfort severity score (mean change from baseline -169, -101, -155, -143, and -138 mm for placebo, and 1.25, 2.5, 5, and 10 mg ABT-229, respectively, at four weeks by intent to treat). The results were not significantly different in those with and without delayed gastric emptying. The severity of bloating, postprandial nausea, epigastric discomfort, heartburn, and acid regurgitation worsened dose dependently in a greater number of patients receiving ABT-229 than placebo. Overall, 63% of patients on placebo reported a good or excellent global response, and this was not different from the active treatment arms.. The motilin agonist ABT-229 was not efficacious in the relief of postprandial symptoms in diabetes mellitus in the presence or absence of delayed gastric emptying.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Breath Tests; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Double-Blind Method; Dyspepsia; Erythromycin; Female; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Humans; Male; Middle Aged; Motilin; Regression Analysis; Treatment Outcome

To investigate the role of motilin in diabetic gastroparesis, we evaluated gastric emptying and plasma concentrations of motilin in diabetic patients. Gastric emptying of radiopaque marker was significantly delayed in the diabetics with autonomic neuropathy (n = 14) compared with the healthy controls (n = 6) (p < 0.01). Mean plasma motilin concentrations were significantly higher in the diabetics with autonomic neuropathy compared with the healthy controls (p < 0.01). A positive correlation was observed between gastric emptying and plasma motilin concentrations in the healthy controls (r = 0.955, p < 0.01), whereas these values were inversely correlated in the diabetics (r = 0.620, p < 0.01). Oral administration of cisapride (15 mg/day.14 day) significantly accelerated gastric emptying without an effect on plasma motilin concentration (p = 0.03). These observations suggest that gastric emptying in the diabetics with autonomic neuropathy is delayed despite elevated levels of motilin, and that cisapride accelerates gastric emptying, independent of the plasma motilin concentration.

Topics: Autonomic Nervous System Diseases; Cisapride; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Female; Gastric Emptying; Humans; Male; Middle Aged; Motilin; Piperidines; Serotonin Antagonists; Stomach Diseases

Zinc is an important co-factor for insulin storage in pancreatic β-cells of different species and the uptake of this ion into insulin containing secretory vesicles is managed by the zinc transporter, ZnT8, a member of the slc30A gene family. Recent studies indicate that this protein is a major autoimmune target in human type 1A diabetes and has also been implicated by genome-wide association studies in type 2 diabetes. Since individuals suffering from type 1 diabetes often develop gastrointestinal motility disorders, we investigated the expression of ZnT8 in the porcine gastrointestinal tract. For this purpose, we studied the cell-type specific expression of ZnT8 in the gut and its co-expression with endocrine hormones that are closely linked to intestinal motility regulation. Nested RT-PCR and immunostaining of sequential serial sections, as well as double-immunostaining using antibodies directed against ZnT8, ghrelin, motilin, neurotensin, serotonin and glucagon-like peptide 1, indicated that ZnT8 is co-localized with ghrelin and motilin. Our findings provide important information about the cell-type specific expression of ZnT8 in the porcine gastrointestinal system. The selective and exclusive expression of ZnT8 in two endocrine cell-types that are engaged in motility functions may be of particular interest for further investigations into type I diabetes-associated gastrointestinal dysfunctions.

Topics: Animals; Cation Transport Proteins; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Disease Models, Animal; Endocrine System; Gastric Mucosa; Gastrointestinal Tract; Gene Expression Profiling; Gene Expression Regulation; Ghrelin; Immunohistochemistry; Intestinal Mucosa; Motilin; Real-Time Polymerase Chain Reaction; Swine

There is little information on the gastrointestinal motility abnormalities and autonomic neuropathy of children with gastrointestinal symptoms and type 1 diabetes mellitus (T1DM).. The authors studied 33 consecutive patients (mean age, 15.3 years; 13 males) with T1DM (median duration, 7.7 years) attending the outpatient clinic because of chronic dyspepsia (CD; n = 14), or chronic constipation (CC; n = 19), and 48 consecutive non-T1DM patients (mean age, 13.7 years; 18 males), who presented with similar symptoms (18 with CD; 30 with CC). Fasting serum motilin concentrations and cardiovascular autonomic function tests (CAFT) were assessed and compared with those of age- and gender-matched healthy control subjects. Gastric emptying half time (GE t1/2) of a solid meal and mouth-to-anus transit time (MATT) were measured in patients with CD and CC, respectively.. CAFT was comparable between patients with T1DM and healthy control subjects. GE t1/2 and MATT were not different between T1DM patients and non-T1DM patients with CD and CC, respectively. However, a marginally significant positive correlation was found in the patients with T1DM between GE t1/2 and blood glucose concentrations (R = 0.54; P = 0.08). In addition, serum motilin concentrations were significantly lower in patients with T1DM compared with healthy control subjects (P < 0.0005), and in patients with T1DM and higher serum glucose concentrations compared with those with lower serum glucose concentrations (P = 0.03).. Autonomic neuropathy is not an etiological factor of gastrointestinal symptoms in children and adolescents with diabetes. Mild or moderate hyperglycemia does not affect gastrointestinal motility.

Topics: Adolescent; Blood Glucose; Case-Control Studies; Child; Constipation; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Dyspepsia; Female; Gastric Emptying; Gastrointestinal Motility; Gastrointestinal Transit; Humans; Hyperglycemia; Male; Motilin

We investigated the efficacy and the mechanism of action of EM523L, a nonpeptide motilin agonist (motilide), on the stimulation of gastric emptying and on the release of gut peptides after ingestion of a solid meat in normal controls (n = 8) and in diabetic patients (n = 8) with signs of neuropathy. A dose of 2 mg EM523L was administered IV over 15 min just after ingestion of a solid meal (200 kcal Gastric emptying was measured by a radionuclide technique. EM523L accelerated gastric emptying and markedly augmented postprandial pancreatic polypeptide (PP) response in both normal control and diabetic patients. This may suggest the mediation of the Vagal-cholinergic pathway to accelerate gastric emptying. The present study offers a promising therapeutic potential of the motilide in gastrointestinal motility disorders like those observed in diabetics mellitus.

Topics: Adult; Aged; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Erythromycin; Evaluation Studies as Topic; Female; Gastric Emptying; Gastrointestinal Agents; Humans; Male; Middle Aged; Motilin; Pancreatic Polypeptide

Experimental euglycaemic hyperinsulinaemia (insulin levels 46 +/- 4 mU/l) impaired the post-absorptive gastrointestinal motility in healthy individuals; the effect being particularly pronounced in the upper gastrointestinal tract (stomach and proximal duodenum). The postprandial gastric emptying, measured with a standardized 99mTc labelled meal, was also significantly delayed (t50 increased by 38% or 32 min). This was combined with a slower carbohydrate absorption (delay in peak blood glucose level about 40 min). Furthermore, during experimental hyperinsulinaemia higher blood glucose levels were seen at 120 min than at 60 min after food ingestion. This was not seen in any subject in the control study where only 0.9% NaCl was infused. Blood levels of the motility-stimulating hormone, motilin, were significantly lower during experimental hyperinsulinaemia. Thus, experimental hyperinsulinaemia impairs the gastrointestinal motility in both the postabsorptive and postprandial states. This effect is combined with a delayed carbohydrate absorption. Hyperinsulinaemia per se may thus lead to alterations in carbohydrate absorption and can also contribute to the gastrointestinal disturbances in diabetes.

Topics: Acute Disease; Adult; Blood Glucose; Diabetes Mellitus, Type 1; Female; Gastrointestinal Motility; Glucose; Humans; Hyperinsulinism; Insulin; Intestinal Absorption; Male; Motilin

To clarify the impact of autonomic neuropathy in diabetic patients, we have conducted a prospective study of 58 Type 1 and 51 Type 2 diabetic patients (investigated at baseline, after 4, and after 7 years). In Type 1 diabetic patients, the sympathetic nerve function (orthostatic acceleration and brake indices) and in Type 2 patients, parasympathetic nerve function (R-R interval variation; E/l ratio) deteriorated during 7 years of prospective observation. Symptoms of autonomic neuropathy were associated with signs of autonomic neuropathy (low brake indices) in Type 1 but not in Type 2 diabetic patients. In the latest assessment 24 h ECG recording was performed and blood samples assayed for neuropeptide Y (NPY) and motilin were obtained. Type 1 diabetic patients with parasympathetic neuropathy (abnormal E/l ratio) showed significantly lower SD value (less variation in the R-R intervals; 29 [17] vs 50 [16], [mean (interquartile range)]; p = 0.001) and higher postprandial plasma motilin values (70 [20] pmol l-1 vs 50 [15] pmol l-1; p < 0.01) than patients with normal parasympathetic nerve function. In Type 2 diabetic patients, sympathetic neuropathy (low brake indices) was associated with an increased frequency of ventricular extra systolic beats during 24 h ECG recording (rs = 0.65; p < 0.01). Postprandial plasma NPY levels were not associated with disturbed autonomic nerve function.

Topics: Adolescent; Adult; Autonomic Pathways; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Electrocardiography, Ambulatory; Female; Heart Rate; Humans; Male; Middle Aged; Motilin; Neuropeptide Y; Prospective Studies

Topics: Autonomic Nervous System Diseases; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Erythromycin; Gastric Emptying; Gastrointestinal Motility; Humans; Motilin; Stomach

Because disturbances of gastric emptying are a serious complication in insulin-dependent diabetic subjects with regard to the maintenance of good metabolic control, we wanted to assess the effectiveness of motilin as a potential treatment for gastric emptying disturbances.. The intestinal hormone motilin has been shown to accelerate gastric emptying in healthy subjects. Therefore, we examined the effect of intravenous motilin on gastric emptying of a 99mTc colloid-labeled semisolid test meal in 9 insulin-dependent diabetic patients with diabetic gastroparesis. All patients had a significantly delayed gastric emptying rate compared with a group of 11 healthy control subjects.. During the infusion of motilin, gastric emptying was accelerated, and it was no longer significantly different from control values.. These data demonstrate that motilin and related compounds such as erythromycin derivatives could be useful for the treatment of disturbed gastric emptying in diabetic subjects.

Topics: Adult; Aged; Diabetes Mellitus, Type 1; Female; Food; Gastric Emptying; Gastrointestinal Transit; Humans; Male; Middle Aged; Motilin; Paralysis; Stomach Diseases; Technetium Tc 99m Sulfur Colloid

The objective of this study is to determine whether abnormal rhythm and amplitude of the oscillation in plasma motilin concentration are responsible for the abnormal motility observed in patients with diabetic gastroparesis. We also investigated the effect of metoclopramide on plasma motilin concentration and gastrointestinal motility in these patients. In healthy controls, basal plasma motilin concentration fluctuated in phase with the interdigestive migrating motor complex. All patients with diabetic gastroparesis did not have antral phase III activities and had significantly higher basal motilin concentrations, which maintained a normal oscillatory pattern. Administration of metoclopramide initiated antral phase III activities in healthy controls and in patients with diabetic gastroparesis. These were accompanied by a concurrent rise in plasma motilin concentration in healthy controls, contrasting with a fall in plasma motilin concentrations in patients with diabetic gastroparesis. We conclude that diabetic gastroparesis is associated with absence of antral interdigestive migrating motor complex and with elevated plasma motilin concentration with normal cyclic fluctuations. Our studies also show that metoclopramide initiates antral phase III activities in diabetic gastroparesis independent of plasma motilin concentration.

Topics: Adolescent; Adult; Diabetes Mellitus, Type 1; Duodenum; Female; Gastrointestinal Hormones; Gastrointestinal Motility; Humans; Jejunum; Male; Metoclopramide; Motilin