Current Pharmaceutical Design - Volume 9, Issue 10, 2003

The blood-brain barrier (BBB) plays a crucial role in the regulation of body weight and feeding by peptides. This review summarizes the components of the BBB as well as the circumventricular organs (CVOs), the methods used for quantification of the passage of feeding peptides across the BBB, and the various ways by which these peptides can interact with the BBB.

Although several possible mechanisms exist by which the pancreatic hormone, insulin, could enter the brain from the blood, most evidence suggests that the majority of it enters primarily by a receptor-mediated transport process. Many factors influence the rate of entry, including fasting and refeeding and several pathological conditions. Within the brain insulin acts on specific receptors to influence a number of be Read More

Leptin has emerged as a major regulator of body adiposity. The majority of humans with obesity have a resistance to leptin. Human and rodent studies indicate that the major cause of this resistance arises from an impaired ability of leptin to cross the blood-brain barrier, with lesser roles played by receptor and post-receptor defects. Evidence from baboons living in the wild is consistent with the hypothesis that during mos Read More

Leptin has been shown to have a wide repertoire of peripheral effects, some of which are mediated through the central nervous system and others that are induced through a direct action on target tissues. There is now evidence showing that leptin exerts some of its metabolic effects acting directly on peripheral tissues. The role of leptin has expanded from a narrow position in obesity to effects on biological processes, such Read More

Amylin is a 37-amino acid peptide hormone that is co-secreted with insulin by pancreatic B cells in response to food intake. Exogenous amylin potently and dosedependently reduces feeding in rats and mice, with both central and peripheral sites being effective. Although amylin has been characterized as a satiety signal that regulates short-term food intake (i.e., meal size), recent data indicate that amylin may have long t Read More

The blood-brain barrier (BBB) mediates interactions between the brain and the cytokines produced in the periphery. Some of these cytokines play significant roles in feeding behavior. This review will summarize various ways by which cytokines cross the BBB and discuss the implications of their transport systems in feeding. For simplicity of discussion, three categories of cytokines are discussed: (1) the proinflammatory cytokines Read More

Diabetes mellitus is a metabolic disorder associated with structural and functional alteration of various organ systems including the central nervous system. The overall evidence suggests that the effect of Diabetes mellitus on the brain, although more subtle than some other chronic diabetic complications, is appreciable. A variety of pathogenetic mechanisms contribute to the central nervous system dysfunction in diabetic pa Read More