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

The pharmacological treatment of obesity should be considered when cannot be achieved a 10% weight loss with diet therapy and physical activity. The drugs effective in obesity treatment may act by different mechanisms such as reduction in food intake, inhibition of fat absorption, increase of thermogenesis and stimulation of adipocyte apoptosis. At present, we only have two marketed drugs for obesity treatment. Sibutramine is an inhibitor of norepinephrine, dopamine and serotonina reuptake which inhibits food intake and increases thermogenesis. Sibutramine administration for a year can induce a weight loss of 4-7%. Its main side effects are hypertension, headache, insomnia and constipation. Orlistat is an inhibitor of pancreatic lipase which is able to block the absorption of 30% of ingested fat. Its administration induces weight loss and reduction of ulterior weight regain. Also, this drug improves hypertension dyslipdaemia and helps to prevent diabetes in 52% of cases when administered over four years. The increase in frequency of stools and interference with vitamin absorption are its main side effects. Glucagon-like peptide 1, which increases insulin sensitivity and satiety, adiponectin and PPAR-gamma agonists which reduce insulin resistance and modulates adipocyte generation are the basis for future therapeutic approaches of obesity. Phosphatase inhibitors induce PPAR-gamma phosphorylation and UCP-1 expression leading to an increase in thermogenesis and reduction in appetite.
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PMID:[Pharmacological treatment of obesity]. 1538 15

The global obesity epidemic fuelled by our obesogenic environment, and the prevention and treatment of obesity are some of the most important health-care challenges of our time. Although influenced largely by genetic factors, body mass index (BMI) is also heavily dependent upon environmental (principally dietary) factors. Whilst bariatric surgery often results in weight loss, its associated cost is prohibitive for widespread application. Current options for medical treatment of obesity are limited by recent withdrawals of Rimonabant and Sibutramine, enhancing the need for further development of novel weight-loss drugs. The incretin effect results from release of the incretin hormones Glucagon like peptide-1 (GLP-1) and Glucose-dependent insulinotropic polypeptide (GIP) from intestinal cells in response to glucose ingestion. This in turn has direct effects on the endocrine pancreas to enhance insulin release in a glucose-dependent manner and suppress glucagon release, the net effects of which are to reduce post-prandial excursions of plasma glucose. Administration of novel GLP-1-mimetic therapies to patients with type 2 diabetes mellitus (T2D) has been shown to improve and stabilise glycaemic control. In addition, such treatment often leads to substantial and sustained weight loss through pleiotropic effects. These include primary central suppressive effects on hypothalamic appetite control and secondary central effects including inhibition of gastric emptying inducing a feeling of fullness during meals. Although not currently licensed for use as weight-loss therapies, application of GLP-1-mimetic drugs for such a purpose would seem to offer great potential, and should be a focus for further research including a full assessment of safety issues.
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PMID:The incretin pathway as a new therapeutic target for obesity. 2065 73