Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We performed fasting and postprandial recordings of antroduodenal manometry in 21 normal volunteers, 13 patients with insulin-dependent diabetes mellitus and gastrointestinal symptoms, and 11 patients with the irritable bowel syndrome. None of the patients or volunteers had previously undergone an intestinal intubation study. Recordings could not be obtained from four of the diabetic patients due to failure to intubate the pylorus. Catheter migration led to incomplete antral data in a further 21% of all recordings. Due to the wide variations demonstrated by the normal volunteers, parameters of either the migrating motor complex (MMC) or the fed response could not differentiate between either of the patient groups and/or the controls. Similarly, while abnormal patterns of either fasting or postprandial motility were common in the diabetic patients, manometry had a sensitivity of only 67% in comparison to the less invasive radionuclide gastric emptying study. Furthermore, manometry failed to identify any diagnostic abnormality in irritable bowel patients; in particular, the incidence of "clustered" contractions was similar in all three groups. We conclude that short duration antroduodenal manometry is of limited diagnostic usefulness due to the difficulties in pyloric intubation in the presence of a dilated stomach and the intrinsic variability in normal motor patterns, perhaps excerbated by the stressful effects of the procedure itself in tube-naive subjects.
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PMID:Antroduodenal manometry. Usefulness and limitations as an outpatient study. 149 59

Alimentary and cardiac autonomic nervous function was assessed in 25 patients with the irritable bowel syndrome. The vagally mediated increase in lower oesophageal sphincter pressure induced by abdominal compression was below that of 25 controls in 13 patients. Efferent vagal function, assessed by the ratio of peak acid output after insulin-induced hypoglycaemia to maximal acid output after pentagastrin, was subnormal in 7 of 23 patients. Pulse rate variability with deep respiration was subnormal in 6 of 23 patients. Abnormality in these tests did not correlate closely with the presence of oesophagitis at endoscopy or with that of gastro-oesophageal reflux on pH monitoring. Thus abnormalities in autonomic nervous reflexes might account for the frequent occurrence of gastro-oesophageal reflux and may be involved in the production of disordered gastrointestinal motility in irritable bowel syndrome.
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PMID:Abnormal vagal function in irritable bowel syndrome. 288 77

Fasting and postprandial levels of gastrin, insulin, gastric inhibitory polypeptide, pancreatic polypeptide, motilin, enteroglucagon and neurotensin were measured in 42 patients with irritable bowel syndrome (IBS). No overall major abnormalities of secretion of any of these peptides were found, although minor differences from normal of pancreatic polypeptide and neurotensin were observed. It is doubtful whether abnormalities of gut hormone secretion play an important role in the pathophysiology of IBS.
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PMID:Gut hormone responses in the irritable bowel syndrome. 721 25

Motility disturbances of the large intestine, which appear in various conditions of a disease, are based on a reduction, the loss or an intensivation of the contractility as well as on a disorganization of the motor activity. Also in the region of the large intestine the normal motoricity can underlie such disturbances, such as retarded or accelerated passage, passage in wrong direction as well as increased turbulence or increased content. Retarded passage of the large intestine leads to obstipation and in advanced form to ileus. The leading symptom in accelerated passage is the diarrhoea. The passage in wrong direction disturbs the motoricity of the colon in the case of a lesion of the ileocaecal valves. Increased turbulence of the content of the large intestine is one of the causes of obstipation, particularly, when it appears in a retarded passage. The disturbances of the laminary flow are characteristic for a diverticulosis. The motor activity of the colon is influenced by many factors, mainly by the central nervous system, the gastrointestinal hormones (cholecystokinin, gastrin, serotonin, insulin and prostaglandins), the diet and the way of life. The motor disturbances are accompanied by bioelectric disturbances of the colon. In the second part of the lecture some pathogenetic and clinical aspects of the most frequently appearing motor disturbance of the large intestine, the irritable colon, are discussed.
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PMID:[Motility disturbances of the large intestine]. 722 37

1. An atypical non beta 1/beta 2-adrenoceptor (AR) subtype (beta 3-AR) has been identified which is selectively stimulated by a group of ligands which mediate lipolytic and thermic responses in brown and white adipose tissue. 2. Molecular studies have shown that beta 3-AR in man are mainly expressed in visceral adipocytes, and to a lesser extent in gall-bladder and colon. In vitro studies with beta 3-AR agonists have shown activity at other sites including skeletal muscle and myocardium. 3. Regulation of beta 3-AR may differ from beta 1/beta 2-AR subtypes in that continuous agonist exposure does not result in receptor down-regulation. 4. A polymorphism of the human beta 3-AR gene (Trp64Arg) has been identified which is associated with obesity, insulin resistance and an earlier onset of non-insulin-dependent diabetes mellitus (NIDDM). Studies are required to establish whether expression of the mutant gene results in altered metabolic responses to beta 3-AR stimulation in man. 5. There is accumulating evidence to support a therapeutic role of beta 3-AR agonists in NIDDM because of anti-obesity and anti-diabetic activity, as a consequence of thermogenic effects as well as increased insulin sensitivity and glucose tolerance. 6. Selectivity studies with BRL35135 and isoprenaline in humans have demonstrated a beta 3-AR mediated component to thermogenesis which is dissociated from beta 1/beta 2-mediated effects on carbohydrate and fat metabolism. Similar studies have suggested a functional beta 3-AR mediating cardiac but not airway responses in humans. An evaluation of beta 3-AR agonists in irritable bowel syndrome may be warranted in view of colonic antimotility properties in vitro.
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PMID:Clinical pharmacology of beta 3-adrenoceptors. 887 18

There is strong evidence that non-insulin-dependent-diabetes mellitus (NIDDM) has a polygenic mode of inheritance. Nevertheless, major gene effects may be involved in its pathogenesis, especially in forms with an early age of onset. We performed linkage analyses between 4 candidate genes for insulin resistance and NIDDM in a set of 55 multigenerational French Caucasian families, using the affected sib-pair approach. No significant results were obtained with glycogen synthase (GSY), insulin receptor substrate-1 (IRS-1) and apolipoprotein C-II (APOC-II) genes. However, a significant trend towards linkage was found between NIDDM and the phosphoenolpyruvate carboxykinase gene (PCK1) located on chromosome 20q (p = 0.005 for the mean estimated proportion of alleles shared identically by descent, mean IBD = 0.55), particularly among sib-pairs with diabetes diagnosed before the age of 46 years (p = 0.0003, mean IBD = 0.66). These results suggest that the PCK1 gene or a nearby locus contributes to the development of NIDDM in the French population.
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PMID:Indication for genetic linkage of the phosphoenolpyruvate carboxykinase (PCK1) gene region on chromosome 20q to non-insulin-dependent diabetes mellitus. 898 54

Few comparative and validated reports exist on the isolation and growth of colonoscopically obtained colonic epithelium. The aim of this study was to develop and validate a simple method for the cultivation of colonoscopically obtained colonocytes. Forty patients, who underwent routine colonoscopy and where the diagnosis of irritable bowel syndrome was later reached, were included. Seven colon biopsies were taken and incubated at varying time periods of 10-120 min and temperatures of 4-37 degrees C in a chelating buffer. The epithelium was then harvested and cultivated under three different conditions: 1) on a collagen coating, 2) embedded in a collagen gel, or 3) embedded in a gel put on a porous well insert. The effect of conditioned medium (CM), insulin, transferrin, selenium, and the oxygen content was assessed. Viability was tested by the metabolic dimethylthiazol-diphenyl-tetrazolium bromide assay, by flowcytometry, by phase contrast microscopy, and by transmission electron microscopy. Incubation at 21 degrees C for 75 min gave an optimal yield of 3 x 10(6) (2.0-3.8 x 10(6)) viable epithelial cells in intact crypts per seven biopsies. Embedding of crypts in a collagen gel put on a porous membrane was superior to the other methods applied [P < 0.003; median viability 71% (62-100%) compared with preculture values] after 24 h, which was a 160% increase in viability compared with coat-cultivated cells. CM had similar viability supporting effects to FCS. Other supplements had no effects. A simple method is presented, which makes cultivation of colonocytes obtained at endoscopy possible for up to 72 h.
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PMID:Simple and efficient method for isolation and cultivation of endoscopically obtained human colonocytes. 1461 19

There is mounting evidence that the vanilloid (capsaicin) receptor; transient receptor potential channel, vanilloid subfamily member 1 (TRPV1), is subjected to multiple interacting levels of control. The first level is by reversible phosphorylation catalyzed by intrinsic kinases (e.g. protein kinase A and C) and phosphatases (e.g. calcineurin), which plays a pivotal role in receptor sensitization vs. tachyphylaxis. In addition, this mechanism links TRPV1 to intracellular signaling by various important endogenous as well as exogenous substances such as bradykinin, ethanol, nicotin and insulin. It is not clear, however, whether phosphorylation per se is sufficient to liberate TRPV1 under the inhibitory control of phosphatydylinositol-4,5-bisphosphate. The second level of control is by forming TRPV1 heteromers and their association with putative regulatory proteins. The next level of regulation is by subcellular compartmentalization. The membrane form of TRPV1 functions as a nonselective cation channel. On the endoplasmic reticulum, TRPV1 is present in two differentially regulated forms, one of which is inositol triphosphate-dependent whereas the other is not. These three TRPV1 compartments provide a versatile regulation of intracellular Ca(2+) levels. Last, there is a complex and poorly understood regulation of TRPV1 activity via control of gene expression. Factors that downregulate TRPV1 expression include vanilloid treatment and growth factor (notably, nerve growth factor) deprivation. By contrast, TRPV1 appears to be upregulated during inflammatory conditions. Interestingly, following experimental nerve injury and in animal models of diabetic neuropathy TRPV1 is present on neurons that do not normally express TRPV1. Combined, these findings imply an important role for aberrant TRPV1 expression in the development of neuropathic pain and hyperalgesia. In humans, disease-related changes in TRPV1 expression have already been described (e.g. inflammatory bowel disease and irritable bowel syndrome). The mechanisms that regulate TRPV1 gene expression under pathological conditions are unknown but a better understanding of these pathways has obvious implications for rational drug development.
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PMID:Biochemical pharmacology of the vanilloid receptor TRPV1. An update. 1512 91

The major modes of presentation of patients with celiac disease are the classic diarrhea-predominant form and silent celiac disease. Those with silent celiac disease lack diarrhea, although they may present with manifestations of celiac disease that include an irritable bowel syndrome, anemia, osteoporosis, neurologic diseases, or malignancy. A significant proportion of patients are diagnosed through screening at-risk groups including relatives of patients and insulin-dependant diabetics. Nondiarrheal presentations now are seen more commonly than those with diarrhea. Patients with celiac disease have a greater burden of disease than the general population because of autoimmune diseases and malignancies. There is a need for screening studies of patients with conditions associated with celiac disease to determine whether the large numbers of people with undiagnosed celiac disease currently are seeking health care.
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PMID:The many faces of celiac disease: clinical presentation of celiac disease in the adult population. 1582 30

We identified a locus on chromosome 6q16.3-q24.2 (ref. 1) associated with childhood obesity that includes 2.4 Mb common to eight genome scans for type 2 diabetes (T2D) or obesity. Analysis of the gene ENPP1 (also called PC-1), a candidate for insulin resistance, in 6,147 subjects showed association between a three-allele risk haplotype (K121Q, IVS20delT-11 and A-->G+1044TGA; QdelTG) and childhood obesity (odds ratio (OR) = 1.69, P = 0.0006), morbid or moderate obesity in adults (OR = 1.50, P = 0.006 or OR = 1.37, P = 0.02, respectively) and T2D (OR = 1.56, P = 0.00002). The Genotype IBD Sharing Test suggested that this obesity-associated ENPP1 risk haplotype contributes to the observed chromosome 6q linkage with childhood obesity. The haplotype confers a higher risk of glucose intolerance and T2D to obese children and their parents and associates with increased serum levels of soluble ENPP1 protein in children. Expression of a long ENPP1 mRNA isoform, which includes the obesity-associated A-->G+1044TGA SNP, was specific for pancreatic islet beta cells, adipocytes and liver. These findings suggest that several variants of ENPP1 have a primary role in mediating insulin resistance and in the development of both obesity and T2D, suggesting that an underlying molecular mechanism is common to both conditions.
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PMID:Variants of ENPP1 are associated with childhood and adult obesity and increase the risk of glucose intolerance and type 2 diabetes. 1602 15


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