ABSTRACT
Globally, 13% of the world's adult population is obese, and more than 400 million people suffer from diabetes. These conditions are both associated with significant morbidity, mortality and financial cost. Therefore, finding new pharmacological treatments is an imperative. Relative hyperglucagonaemia is seen in all types of diabetes, and has been implicated in its pathogenesis. Consequently, clinical trials are underway using drugs which block glucagon activity to treat type 2 diabetes. Conversely, exogenous glucagon can increase energy expenditure. Therefore, researchers are designing peptides that combine activation of the glucagon receptor with further incretin properties, which will treat obesity while mitigating the hyperglycaemic effects of glucagon. This review will discuss these conflicting physiological properties of glucagon, and the attempts to harness these effects pharmacologically.
Subject(s)
Glucagon/therapeutic use , Hyperglycemia/drug therapy , Incretins/therapeutic use , Obesity/drug therapy , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Energy Metabolism/drug effects , Glucagon/metabolism , Humans , Hyperglycemia/complications , Hyperglycemia/metabolism , Incretins/metabolism , Insulin/metabolism , Insulin/therapeutic use , Obesity/complications , Obesity/metabolism , Receptors, Glucagon/chemistry , Receptors, Glucagon/geneticsABSTRACT
Bayliss and Starling first coined the term 'hormone' with reference to secretin, a substance they found that was produced by the gut, but released into the blood stream to act at a distance. The intestine is now known as the largest endocrine organ in the body, and it produces numerous hormones with a wide range of functions. These include controlling appetite and energy homeostasis. Obesity is one of the greatest health threats facing the world today. At present, the only successful treatment is surgery. Bariatric procedures such as the Roux-en-Y bypass work by elevating gut hormones that induce satiety. Significant research has gone into producing versions of these hormones that can be delivered therapeutically to treat obesity. This review looks at the role of gut hormones in obesity, and the development of gut hormone-derived obesity treatments.
Subject(s)
Gastrointestinal Hormones/physiology , Gastrointestinal Hormones/therapeutic use , Obesity/physiopathology , Obesity/therapy , Animals , Appetite/physiology , Appetite Regulation/physiology , Awards and Prizes , Bariatric Surgery , Energy Metabolism/physiology , Female , Glucagon-Like Peptide 1/physiology , Glucagon-Like Peptide 1/therapeutic use , Humans , Male , Obesity/epidemiology , Pandemics , Peptide YY/physiology , Peptide YY/therapeutic use , Societies, ScientificABSTRACT
A case of prenatally diagnosed true mosaicism for trisomy 5 with a clinically normal outcome is presented. Trisomy 5 was detected in 23% of cells obtained by amniocentesis, but it was not detected from cells obtained by fetal blood sampling. While in this case the finding at amniocentesis did not reflect the status of the fetus, care must be exercised in reaching this conclusion in all cases.
