Peptides and their potential role in the treatment of diabetes and obesity

Abstract

It is estimated that 347 million people worldwide have diabetes and that over 1.5 billion adults worldwide are overweight. Predictions suggest these rates are increasing. Diabetes is a common complication in overweight and obese subjects, and in 2004, an estimated 3.4 million people died from consequences of high blood sugar. Thus, there is great interest in revealing the physiological systems that regulate body weight and blood sugar. Several peptidergic systems within the central nervous system and the periphery regulate energy homeostasis. A number of these systems have been investigated as potential treatments for obesity and the metabolic syndrome. However, manipulation of peptidergic systems poses many problems. This review discusses the peptidergic systems currently attracting research interest for their clinical potential to treat obesity. We consider first neuropeptides in the brain, including the orexigenic neuropeptide Y and melanin-concentrating hormone, and anorectic factors such as the melanocortins, ciliary neurotrophic factor, and neuromedin U. We subsequently discuss the utility of targeting peripheral gut peptides, including pancreatic polypeptide, peptide YY, amylin, and the gastric hormone ghrelin. Also, we analyze the evidence that these factors or drugs based on them may be therapeutically useful, while considering the disadvantages of using such peptides in a clinical context.

Figure 1

Schematic diagram illustrating the peptidergic signaling pathways regulating energy homeostasis. Peptides colored blue are orexigenic, promoting hunger, whilst peptides colored red are anorexigenic, promoting satiety. POMC: pro-opiomelanocortin. NPY: neuropeptide Y. AgRP: agouti-related peptide. NMU: neuromedin U. CNTF: ciliary neurotrophic factor. MCH: melanin concentrating hormone. PYY3-36: peptide YY3-36. PP: pancreatic polypeptide. BBB: blood-brain barrier.