motilin and Diabetes-Mellitus--Type-2

Obesity is a multi-gene syndrome, expression of which is modulated not only by environmental factors but above all by a number of modified genes interacting with each other. Among candidate genes related to obesity phenotype is ghrelin gene. Ghrelin plays a significant role in feeding regulation and is the strongest stimulator of growth hormone secretion. Ghrelin acts by GHS1a receptor (growth hormone secretagogue receptor). Mutations in preproghrelin and ghrelin gene or ghrelin receptor gene could be responsible for low ghrelin levels observed in obese individuals. Among identificated mutations, two Arg51 Gln and Leu72Met are most often described and change amino-acid sequence of ghrelin (Arg51Gln) and preproghrelin (Leu72Met). Although no direct relationship between Arg51Gln mutation and obesity phenotype was found, it had been shown that carriers of Arg51Gln mutation had significantly decreased plasma ghrelin levels. Furthermore 51Gln allele carriers had higher prevalence of type 2 diabetes mellitus and hypertension than non-carriers. Met 72 carrier status is associated with higher serum IGF-1 levels and seems to be a protective factor against fat accumulation and cardiovascular complications of obesity. No evidence of relationship between ghrelin receptor gene polymorphisms and body mass regulation was found, however, until now there is no study on relationships between these polymorphisms and metabolic complications of obesity. The presence of genetic variants in ghrelin or GHS receptor gene could be responsible for impaired GH secretion in visceral type obesity and development of metabolic syndrome in some of obese subjects. On the other hand, some mutations in preproghrelin gene could be protective against metabolic syndrome.

Topics: Diabetes Mellitus, Type 2; Ghrelin; Humans; Metabolic Syndrome; Motilin; Mutation; Obesity; Peptide Hormones; Polymorphism, Genetic; Receptors, G-Protein-Coupled; Receptors, Ghrelin

The influence of a beet-fibre enriched diet (mean 40 g FibrexR, 27 g dietary fibre per day) on blood pressure, plasma lipoproteins and glycaemic control was studied in 12 non-insulin-dependent diabetic (NIDD) patients. The effect on gastrointestinal hormones was also investigated. Beet-fibre and control diets were given in randomized order for 8 weeks each. During the beet-fibre diet the systolic blood pressure decreased (P less than 0.05) and the HDL-cholesterol levels increased (P less than 0.05) compared to values before the study. There was a tendency for systolic blood pressure to be lower also in the control period, but this was not statistically significant. After both diet periods the total plasma cholesterol and triglyceride levels decreased, as well as the LDL/HDL ratio. Blood glucose levels--fasting or postprandial--and glycosylated haemoglobin were not affected during the two different diet periods. In obese NIDD patients, however, the postprandial insulin levels were lower after the beet-fibre diet compared to the control diet. This subgroup also showed lower fasting values of pancreatic polypeptide and motilin were recorded for the obese patients after the fibre-rich period compared to before the study. Further, increases in postprandial motilin levels, 60-180 min, were found after the fibre-rich period. Investigations with reference to an entero-hormonal mechanism by measuring neurotensin and peptide YY did not show any variations between the diet periods.

Topics: Adult; Aged; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Dietary Fiber; Female; Gastrointestinal Hormones; Humans; Lipoproteins; Male; Middle Aged; Motilin; Neurotensin; Pancreatic Polypeptide; Sweden

Topics: Cholecystokinin; Diabetes Mellitus, Type 2; Digestive System Physiological Phenomena; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Humans; Insulin; Motilin; Neurotensin; Obesity; Pancreatic Polypeptide; Pentagastrin; Secretin; Somatostatin; Vasoactive Intestinal Peptide

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

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

The influence of a beet-fibre enriched diet (mean 40 g FibrexR, 27 g dietary fibre per day) on blood pressure, plasma lipoproteins and glycaemic control was studied in 12 non-insulin-dependent diabetic (NIDD) patients. The effect on gastrointestinal hormones was also investigated. Beet-fibre and control diets were given in randomized order for 8 weeks each. During the beet-fibre diet the systolic blood pressure decreased (P less than 0.05) and the HDL-cholesterol levels increased (P less than 0.05) compared to values before the study. There was a tendency for systolic blood pressure to be lower also in the control period, but this was not statistically significant. After both diet periods the total plasma cholesterol and triglyceride levels decreased, as well as the LDL/HDL ratio. Blood glucose levels--fasting or postprandial--and glycosylated haemoglobin were not affected during the two different diet periods. In obese NIDD patients, however, the postprandial insulin levels were lower after the beet-fibre diet compared to the control diet. This subgroup also showed lower fasting values of pancreatic polypeptide and motilin were recorded for the obese patients after the fibre-rich period compared to before the study. Further, increases in postprandial motilin levels, 60-180 min, were found after the fibre-rich period. Investigations with reference to an entero-hormonal mechanism by measuring neurotensin and peptide YY did not show any variations between the diet periods.

Topics: Adult; Aged; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Dietary Fiber; Female; Gastrointestinal Hormones; Humans; Lipoproteins; Male; Middle Aged; Motilin; Neurotensin; Pancreatic Polypeptide; Sweden

Seventeen non-insulin-dependent diabetics poorly controlled by diet and sulphonylurea drugs took part in a long-term (20-52 weeks) trial of the effect of an alpha-glucosidase inhibitor (acarbose 100 mg thrice daily) on postprandial glycaemic and gastro-entero-pancreatic hormone responses. Patients were assessed before, during, and after the trial period with identical 2.2 MJ mixed test meals plus placebo or acarbose 100 mg, and sulphonylurea therapy was continued throughout. Acarbose administration reduced the integrated postprandial plasma responses of glucose to 58 +/- 10% (mean +/- SEM, p less than 0.001), insulin to 61 +/- 10% (p less than 0.01) and gastric inhibitory polypeptide to 45 +/- 8% (p less than 0.001) of control values, increased the enteroglucagon response to 152 +/- 26% (p less than 0.001) of control and slightly prolonged the postprandial release of motilin. Recorded glycosuria was significantly (p less than 0.01) reduced throughout the treatment period. The effects of acarbose on postprandial glycaemic and endocrine responses remained approximately constant throughout the trial period, and responses returned to pre-treatment values within 2 days of stopping treatment.

Topics: Acarbose; Adolescent; Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Fasting; Female; Follow-Up Studies; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon-Like Peptides; Glycoside Hydrolase Inhibitors; Humans; Insulin; Lipids; Male; Middle Aged; Motilin; Pancreatic Hormones; Patient Compliance; Sulfonylurea Compounds; Time Factors; Trisaccharides

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

Ghrelin is a novel gut-brain peptide, which exerts somatotropic, orexigenic, and adipogenic effects. Genetic variants of ghrelin have been associated with both obesity and insulin metabolism. In this study, we determined a role of preproghrelin Leu72Met polymorphism on type 2 diabetes mellitus and its relationship to variables studied. Genotypes were assessed by polymerase chain reaction. Frequencies of the Leu72Met polymorphism were found to be 35.4% in the type 2 diabetic patients and 32.5% in the normal controls. The Leu72Met polymorphism was not associated with hypertension, macroangiopathy, retinopathy, serum cholesterol, triglyceride, blood urea nitrogen, HbA(1c), lipoprotein (a), fasting insulin, or 24-hour urinary protein levels in the type 2 diabetic group. However, the Leu72Met polymorphism was clearly associated with serum creatinine levels in the diabetic group, as the Met72 carriers exhibited lower serum creatinine levels than the Met72 noncarriers. Our data indicate that the preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus. However, the Leu72Met polymorphism is associated with serum creatinine levels. These data suggest that Met72 carrier status may be a predictable marker for diabetic nephropathy or renal impairment in type 2 diabetes mellitus.

Topics: Aged; Case-Control Studies; Creatinine; Diabetes Mellitus, Type 2; Female; Gene Frequency; Genotype; Ghrelin; Humans; Male; Middle Aged; Motilin; Mutation, Missense; Polymorphism, Genetic

Ghrelin is a novel peptide hormone, which exerts somatotropic, orexigenic and adipogenic effects. Recent studies have shown that the preproghrelin Leu72Met polymorphism is associated with serum creatinine (Scr) concentration in type 2 diabetes; 72Met carriers exhibited lower Scr levels as compared with the 72Met non-carriers. We hypothesized that the preproghrelin Leu72Met polymorphism is associated with a lower rate of developing renal dysfunction in patients with type 2 diabetic nephropathy.. The preproghrelin Leu72Met polymorphism was investigated using PCR techniques in 138 patients with diabetic nephropathy divided into two groups, one with normal renal function and the other with renal dysfunction.. Determination of the frequency of the preproghrelin Leu72Met polymorphism was the main outcome measure.. The frequency of the Leu72Met polymorphism in diabetic nephropathy was significantly lower in patients with renal dysfunction (15.9%, P < 0.01) than in patients with normal renal function (42.0%) or in the diabetes control group (40.6%). The Leu72Met polymorphism was also associated with serum total cholesterol levels in diabetic nephropathy patients with renal dysfunction; the 72Met carriers had lower total cholesterol levels than the 72Met non-carriers (P < 0.05).. These data suggest that 72Met carrier status may be used as a marker predicting a lower chance of developing renal dysfunction in diabetic nephropathy.

Topics: Amino Acid Substitution; Anthropometry; Diabetes Mellitus, Type 2; Diabetic Nephropathies; DNA; Female; Gene Frequency; Genotype; Ghrelin; Humans; Lipids; Male; Middle Aged; Motilin; Mutation; Polymorphism, Genetic

To investigate the preproghrelin gene for variants and their association with obesity and type 2 diabetes.. 82 obese probands were analyzed for mutations using single-strand conformational polymorphism, heteroduplex analyses and sequencing. Association studies were performed in 234 juvenile-onset obese and 323 lean men and in 557 type 2 diabetic and 233 glucose tolerant subjects.. We identified two novel variants, 36C > T and IVS3 + 715delC, and 4 known variants, Arg51Gln, Leu72Met, Gln90Leu, and IVS1 + 169G > A. None of the variants showed any significant association with obesity or type 2 diabetes or estimates of glucose and lipid metabolism in glucose tolerant subjects.. Variation in the preproghrelin gene is not associated with juvenile-onset obesity, type 2 diabetes or related phenotypes among the examined Danish Caucasian subjects.

Topics: Adolescent; Adult; Case-Control Studies; Cohort Studies; Denmark; Diabetes Mellitus, Type 2; DNA Mutational Analysis; Female; Genotype; Ghrelin; Humans; Male; Middle Aged; Motilin; Obesity; Polymorphism, Genetic

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

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