Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastroparesis, constipation, diarrhea, and fecal incontinence occur frequently in diabetics with long-standing and often poorly controlled insulin-dependent diabetes. These motor abnormalities of the gastrointestinal tract tend to be associated in these patients with evidence of autonomic neuropathy and other diabetes-related complications such as peripheral neuropathy, nephropathy, and retinopathy. The management of these derangements of motility is generally frustrating and very difficult. The prokinetic agents currently available have fewer side effects than previously used drugs, and have expanded the treatment options for diabetics with motility disorders of the gastrointestinal tract. The treatment of diabetic diarrhea remains aimed at the symptom because the cause is often unknown. The diagnosis of diabetic diarrhea depends on a careful and judicious assessment, which allows for the distinction of this condition from other causes of diarrhea. For example, celiac disease can occur in insulin-dependent diabetics, but it is specifically treated by the elimination of gluten from the diet. In recent years, we have also gained a better understanding of the liver and biliary tree abnormalities that occur in the diabetic. The most common hepatobiliary lesions found in these patients include excessive glycogen deposition, fatty liver, and gallstones. Cirrhosis of the liver can develop in diabetics as a result of progressive fatty steatosis, pericentral hepatic fibrosis, and, at times, central hyaline sclerosis. Future study of the underlying pathogenesis of diabetes may one day allow us to find common threads in the seemingly disparate gastrointestinal and hepatic complications of this disease.
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PMID:The intestinal and liver complications of diabetes mellitus. 843 40

1. Diabetes mellitus is common in patients with cirrhosis; patients with DM undergoing liver transplantation often have many other co-morbid illnesses including obesity, coronary artery disease (CAD), autonomic neuropathy, gastroparesis, and nephropathy. 2. Long-term survival of patients with diabetes mellitus (DM) is significantly lower and morbidity higher when compared to non-diabetics mainly because of cardiovascular complications, infections, and renal failure. 3. Obesity, CAD, and renal failure are confounding factors that result in poor patient survival. 4. Patients with DM should undergo careful cardiovascular diagnostic work up, including routine coronary arteriogram, and necessary interventions before liver transplantation. This is especially important in those over 50 years old, and in those with retinopathy, nephropathy, and neuropathy. 5. Patients with coronary artery disease that is not amenable to surgery or stents, and those with impaired left ventricular function, should not be considered for liver transplantation. Other relative or absolute contraindications are those with proteinura and renal failure who are not candidates for combined liver/kidney transplantation, those with severe gastroparesis, especially when it is associated with diabetic autonomic neuropathy, and those with two or more risk factors such as CAD, morbid obesity, and renal failure. 6. Future studies should focus on risk stratification of patients with DM undergoing liver transplantation and better interventions to reduce the risk of diabetic complications before and after liver transplantation.
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PMID:When is diabetes mellitus a relative or absolute contraindication to liver transplantation? 1623 83

A breakthrough using "reverse pharmacology" identified and characterized acyl ghrelin from the stomach as the endogenous cognate ligand for the growth hormone (GH) secretagogue receptor (GHS-R) 1a. The unique post-translational modification of O-n-octanoylation at serine 3 is the first in peptide discovery history and is essential for GH-releasing ability. Des-acyl ghrelin, lacking O-n-octanoylation at serine 3, is also produced in the stomach and remains the major molecular form secreted into the circulation. The third ghrelin gene product, obestatin, a novel 23-amino acid peptide identified from rat stomach, was found by comparative genomic analysis. Three ghrelin gene products actively participate in modulating appetite, adipogenesis, gut motility, glucose metabolism, cell proliferation, immune, sleep, memory, anxiety, cognition, and stress. Knockdown or knockout of acyl ghrelin and/or GHS-R1a, and overexpression of des-acyl ghrelin show benefits in the therapy of obesity and metabolic syndrome. By contrast, agonism of acyl ghrelin and/or GHS-R1a could combat human anorexia-cachexia, including anorexia nervosa, chronic heart failure, chronic obstructive pulmonary disease, liver cirrhosis, chronic kidney disease, burn, and postsurgery recovery, as well as restore gut dysmotility, such as diabetic or neurogenic gastroparesis, and postoperative ileus. The ghrelin acyl-modifying enzyme, ghrelin O-Acyltransferase (GOAT), which attaches octanoate to serine-3 of ghrelin, has been identified and characterized also from the stomach. To date, ghrelin is the only protein to be octanylated, and inhibition of GOAT may have effects only on the stomach and is unlikely to affect the synthesis of other proteins. GOAT may provide a critical molecular target in developing novel therapeutics for obesity and type 2 diabetes.
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PMID:Ghrelin gene products and the regulation of food intake and gut motility. 2003 70

Gastroparesis has long been associated with diabetes mellitus or autonomic dysfunction in general. Unfortunately, this condition has never been explored sufficiently in liver cirrhosis patients, although a significant number of them have gastrointestinal symptoms usually explained by the presence of ascites or splenomegaly. The patient experience described in this report is not an uncommon situation. We present it to bring his case to the reader's attention, so they can keep liver cirrhosis in mind as a potential cause of gastroparesis. The main goal of this brief report is to shed light on this important subject and to stress the need for further research in this area.
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PMID:The Forgotten Cause of Gastroparesis: Liver Cirrhosis. 3085 31