Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Maintaining glycemic control is the primary goal for preventing macrovascular and microvascular complications associated with type 2 diabetes. Currently available antidiabetic drugs work in different ways to lower blood glucose levels; unfortunately, each of them has its tolerability and safety concerns. Exenatide is the first drug in a new class known as the incretin mimetic agents. It improves glucose control by mimicking the effects of glucagon-like peptide-1, a natural mammalian incretin hormone secreted during food intake. Exenatide was approved by the U.S. Food and Drug Administration for the treatment of type 2 diabetes in conjunction with metformin and/or sulfonylurea. The recommended dosage is 5 mug to 10 mug twice daily subcutaneously before breakfast and dinner. In randomized, placebo-controlled, 30-week clinical studies, exenatide improved glycemic control and promoted weight loss of up to 2.8 kg. The most common adverse effects were nausea (44%), vomiting (13%), diarrhea (13%), and hypoglycemia (5-36%). Hypoglycemia occurred in a dose-dependent fashion. Patients should be closely monitored for hypoglycemia, especially when exenatide is added to sulfonylurea therapy. Overall, exenatide provides a treatment option for patients with type 2 diabetes who fail to obtain glycemic control while on a maximum dose of metformin and/or sulfonylurea therapy. It is also an alternative therapy for those patients who cannot tolerate other antidiabetic drugs.
 ...
PMID:Exenatide: a novel incretin mimetic agent for treating type 2 diabetes mellitus. 1678 34

Multiple endocrine neoplasm type 1 (MEN1) syndrome predisposes to the development of endocrine and non-endocrine tumors with an autosomal dominant pattern of inheritance. Different mutations have been found throughout the gene with a variable phenotype expression. The proband, a Caucasian man, was admitted to our department in 2001, at the age of 51 because of a 1-yr history of diarrhoea and hypertension. He reported a previous intestinal resection for bowel occlusion with a histological diagnosis of unspecified mesenchymal neoplasia. He had also undergone a left adrenalectomy for a large nonfunctioning adrenal adenoma. Subsequently, he had suffered from gastralgia and melena; a gastroduodenoscopy showed an erosive gastritis. His family history was negative for endocrine disorders. On physical examination, multiple abdominal cutaneous lipomas and facial angiofibromas were observed. Biochemical screening revealed a primary hyperparathyroidism and an increase in circulating levels of PRL, chromogranin-A, gastrin and glucagon. The whole body computed tomography (CT) scan, the 111In-octreotide scan and the pituitary magnetic resonance imaging (MRI) did not reveal any abnormality. The presence of small neuroendocrine tumors was suspected by a positron emission tomography uptake in the epigastric region. The endoscopic ultrasound revealed a pancreatic lesion sized 1.1 cm that is under evaluation. Direct DNA sequencing analysis of the proband MEN1 gene revealed the 579delG frameshift mutation in the exon 3. The genetic screening of the family revealed the same mutation in 3 out of 5 offspring. The biochemical screening revealed some features of the MEN1 syndrome in all three of them. In conclusion, a novel frameshift MEN1 mutation was found in kindred with an apparently negative family history. Our experience confirms that MEN1 syndrome is a complex and underestimated condition, unless specifically investigated by trained specialists.
 ...
PMID:MEN1 family with a novel frameshift mutation. 1679 69

Diarrhoea is a common complication of enteral feeding. Previous studies have demonstrated a secretion of water and electrolytes in the ascending colon during intragastric but not intraduodenal enteral feeding. The cause of this secretion is likely to be neurohumoral in origin. This study was designed to examine the hormonal responses to enteral feeding. In vivo segmental colonic perfusion studies were undertaken. Before and at hourly intervals during these studies serum was taken for estimations of neurotensin (NT), pancreatic glucagon (PG), peptide YY (PYY) and vasoactive intestinal polypeptide (VIP). During fasting there was a median ascending colonic absorption of water in all groups. During feeding there was a net secretion in the ascending colon in both gastric groups and in the high load duodenal group, but not in the low load duodenal group. During these studies the PYY levels remained unchanged from fasting in the low and high load gastric groups. In the low and high load duodenal groups the PYY levels increased. The NT levels increased only in the high load duodenal group. There were no other changes in NT or in PG or VIP levels either between fasting and feeding, or between the gastric and duodenal groups. PYY is known to stimulate intestinal absorption. The absence of a rise during intragastric feeding may be important in the underlying mechanisms of enteral feeding-induced colonic secretion and hence enteral feeding-related diarrhoea.
 ...
PMID:Hormonal response to enteral feeding and the possible role of peptide YY in pathogenesis of enteral feeding-related diarrhoea. 1684 62

Somatostatinoma is a rare neoplasm usually arising from the pancreas and duodenum which typically presents with indolent, nonspecific symptoms in the absence of systemic neuroendocrine manifestations that characterize somatostatinoma syndrome. It accounts for less than 1% of all gastrointestinal endocrine tumors with an annual incidence of 1 per 40 million. It is often associated with regional and/or portal metastasis at the time of diagnosis, and complete tumor resection is possible only in 60% to 70% of cases. We experienced a case of pancreatic somatostatinoma recently. A 51-year-old woman presented with right upper quadrant abdominal pain and loose stool for one month. A hypermetabolic lesion in the pancreatic head was detected on positron emission tomography-CT (PET-CT) scan. The tumor was resected by pylorus preserving pancreaticoduodenectomy. Immunohistochemical staining of the tumor tissue exhibited diffuse positivity for somatostatin, but was negative for insulin and glucagon. Herein, we report a case of pancreatic somatostatinoma diagnosed postoperatively.
 ...
PMID:[A case of pancreatic somatostatinoma]. 1713 24

The incretin hormones are intestinal peptides that enhance insulin secretion following ingestion of nutrients. Liraglutide is a glucagon-like peptide-1 receptor analogue, which is obtained by derivatising glucagon-like peptide-1 with a fatty acid, providing a compound with pharmacokinetic properties that are suitable for once-daily dosing. Liraglutide has demonstrated lasting improvement of HbA(1c )levels, weight reduction and improved beta-cell function in patients with Type 2 diabetes mellitus. Liraglutide is well tolerated; the adverse events that are most frequently reported being transient nausea and diarrhoea. This article reviews the mechanisms of action and efficacy of liraglutide for the treatment of Type 2 diabetes mellitus. This agent is presently in Phase III clinical development.
 ...
PMID:Liraglutide: a once-daily GLP-1 analogue for the treatment of type 2 diabetes mellitus. 1724 43

Exenatide is the first drug in the incretin mimetic class and is indicated for treatment of type 2 diabetes mellitus. Although structurally similar to the native glucagon-like peptide, this synthetic form has a much longer duration of action. Randomized trials have shown exenatide to be efficacious in improving glycemic control when combined with either metformin or a sulfonylurea. The dose is initially 5 mcg subcutaneously twice daily and may be titrated to 10 mcg subcutaneously twice daily to achieve better diabetes management. Nausea, vomiting, and diarrhea were the most common adverse events reported with exenatide therapy. Exenatide is not associated with hypoglycemia, which may provide advantages over adding insulin to a sulfonylurea or metformin.
 ...
PMID:Exenatide (Byetta) as a novel treatment option for type 2 diabetes mellitus. 1725 50

The response to oral glucose was examined in 10 obese and 9 lean age-matched, neutered cats. In all cats, oral administration of 2g/kg glucose was followed by a prompt increase in glucose, insulin, and glucagon-like peptide (GLP)-1. There were significant differences between lean and obese cats in the areas under the curve for glucose, insulin, and GLP-1. However, the responses were variable, and a clear distinction between individual lean and obese cats was not possible. Therefore, this test cannot be recommended as a routine test to examine insulin resistance in individual cats as it is used in people. A further disadvantage for routine use is also the fact that this test requires gastric tubing for the correct administration of the glucose and associated tranquilization to minimize stress and that it was associated with development of diarrhea in 25% of the cats. GLP-1 concentrations were much lower in obese than lean cats. The low GLP-1 concentrations in obese cats might indicate a contribution of GLP-1 to the lower insulin sensitivity of obese cats, but this hypothesis needs to be further investigated.
 ...
PMID:Oral glucose leads to a differential response in glucose, insulin, and GLP-1 in lean versus obese cats. 1978 90

The outcome for children with congenital enteropathies or massive surgical resections has improved significantly over the past two decades. Advances in understanding of the pathophysiology of intractable diarrhea and of the mutations causing many of the congenital enteropathies have enabled initiation of preventive measures for intractable diarrhea, and have enabled clinicians to provide focused treatment of immune-mediated congenital diarrheal illnesses. Children with surgical short bowel syndrome also face an improved outcome because of improvements in the composition of parenteral nutrition (TPN) and in enteral alimentation strategies. It is now recognized that, through adaptation, small intestinal surface area and absorptive function may improve over time to facilitate emancipation from parenteral nutrition. Beyond provision of enteral nutrition, ancillary therapies such as judicious use of acid suppression, antibiotics, prokinetic agents, and soluble fiber seem to accelerate the rate of adaptation in young children. In the future, trophic hormones such as epidermal growth factor (EGF) or glucagon-like peptide 2 (GLP-2) may become routine members of the therapeutic armamentarium for surgical short bowel syndrome, thus further improving outcomes.
 ...
PMID:Medical management of pediatric intestinal failure. 2012 70

In an intensive livestock production, a shorter suckling period allows more piglets to be born. However, this practice leads to a number of disorders including nutrient malabsorption, resulting in diarrhoea, malnutrition and dehydration. A number of strategies have been proposed to overcome weaning problems. Artificial sweeteners, routinely included in piglets' diet, were thought to enhance feed palatability. However, it is shown in rodent models that when included in the diet, they enhance the expression of Na+/glucose co-transporter (SGLT1) and the capacity of the gut to absorb glucose. Here, we show that supplementation of piglets' feed with a combination of artificial sweeteners saccharin and neohesperidin dihydrochalcone enhances the expression of SGLT1 and intestinal glucose transport function. Artificial sweeteners are known to act on the intestinal sweet taste receptor T1R2/T1R3 and its partner G-protein, gustducin, to activate pathways leading to SGLT1 up-regulation. Here, we demonstrate that T1R2, T1R3 and gustducin are expressed together in the enteroendocrine cells of piglet intestine. Furthermore, gut hormones secreted by the endocrine cells in response to dietary carbohydrates, glucagon-like peptides (GLP)-1, GLP-2 and glucose-dependent insulinotrophic peptide (GIP), are co-expressed with type 1 G-protein-coupled receptors (T1R) and gustducin, indicating that L- and K-enteroendocrine cells express these taste elements. In a fewer endocrine cells, T1R are also co-expressed with serotonin. Lactisole, an inhibitor of human T1R3, had no inhibitory effect on sweetener-induced SGLT1 up-regulation in piglet intestine. A better understanding of the mechanism(s) involved in sweetener up-regulation of SGLT1 will allow the identification of nutritional targets with implications for the prevention of weaning-related malabsorption.
 ...
PMID:Expression of Na+/glucose co-transporter 1 (SGLT1) is enhanced by supplementation of the diet of weaning piglets with artificial sweeteners. 2033 74

Aristaless-related homeobox gene (ARX) mutation leads to several neurological disorders including X-linked lissencephaly with abnormal genitalia (XLAG), West syndrome and Partington syndrome, with XLAG being the most severe form. Although some of the brain pathologies of XLAG have already been described, the crucial extra-brain symptoms are severe growth retardation, transient hyperglycemia and intractable diarrhea. Since ARX expresses in the islets of Langerhans during the embryonic stage, these visceral phenotypes may be related to a loss of ARX function, which develops endocrine cells in the pancreas. We investigated the abnormal pancreatic development of XLAG patients with ARX-null mutation. We performed immunohistochemistry of XLAG pancreases, using the antibodies against glucagon, insulin, somatostatin, pancreatic polypeptide, ghrelin, Brn4, Nkx2.2, Mash1, amylase and pancreatic lipase. As the results, the glucagon- and pancreatic polypeptide-producing cells were found to be completely deficient in the islets of Langerhans. We also discovered marked interstitial fibrosis, small exocrine cells with loss of amylase-producing cells and an enlargement of the central lumen of the glandular acini. These pathological findings indicate that ARX contributes not only to endocrine development, but also to exocrine development of the human pancreas, and its deficiency may lead to the severe phenotypes of XLAG patients.
 ...
PMID:Partial loss of pancreas endocrine and exocrine cells of human ARX-null mutation: consideration of pancreas differentiation. 2053 4


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>