The incretin pathway as a new therapeutic target for obesity.
Summary of "The incretin pathway as a new therapeutic target for obesity."
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.
Affiliation
Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford OX3 7LJ, United Kingdom.
Journal Details
This article was published in the following journal.
Name: Maturitas
ISSN: 1873-4111
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20655673
- DOI: http://dx.doi.org/10.1016/j.maturitas.2010.06.018
Medical and Biotech [MESH] Definitions
Obesity, Abdominal
A condition of having excess fat in the abdomen. Abdominal obesity is typically defined as waist circumferences of 40 inches or more in men and 35 inches or more in women. Abdominal obesity raises the risk of developing disorders, such as diabetes, hypertension and METABOLIC SYNDROME X.
Fatty Acid Synthetase Complex, Type I
Animal form of fatty acid synthase which is encoded by a single gene and consists of seven catalytic domains and is functional as a homodimer. It is overexpressed in some NEOPLASMS and is a target in humans of some ANTINEOPLASTIC AGENTS and some ANTI-OBESITY AGENTS.
Obesity, Morbid
The condition of weighing two, three, or more times the ideal weight, so called because it is associated with many serious and life-threatening disorders. In the BODY MASS INDEX, morbid obesity is defined as having a BMI greater than 40.0 kg/m2.
Receptors, Leptin
Cell surface receptors for obesity factor (LEPTIN), a hormone secreted by the WHITE ADIPOCYTES. Upon leptin-receptor interaction, the signal is mediated through the JAK2/STAT3 pathway to regulate food intake, energy balance and fat storage.
Insulin Resistance
Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS. It can be caused by the presence of INSULIN ANTIBODIES or the abnormalities in insulin receptors (RECEPTOR, INSULIN) on target cell surfaces. It is often associated with OBESITY; DIABETIC KETOACIDOSIS; INFECTION; and certain rare conditions. (from Stedman, 25th ed)
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