Figure 4.

Biological functions of apelin in glucose metabolism, lipid metabolism, and water metabolism. Glucose metabolism: apelin promotes glucose uptake in skeletal muscle cells and adipose tissues, and increases overall glucose utilization; it also increases glucose uptake and Glut4 membrane translocation in mouse myocardium in vivo; it increases the net glucose flow of gastrointestinal mucosal barrier and enhances the glucose transport from intestinal lumen to blood in the intestinal epithelium; it improves glucose utilization by the decrease of enteric nervous system (ENS)-evoked duodenal contraction activities; and it regulates glucose homeostasis and promotes glucose uptake and utilization in the brain of the normally fed mice. High concentrations of apelin reduce systemic sensitivity to insulin and produce insulin resistance, activate the sympathetic nervous system through reactive oxygen species (ROS) signaling pathways, and promote hepatic glycogenolysis and gluconeogenesis in the brain of obese or diabetic mice. Lipid metabolism: apelin increases perilipin content around lipid vesicles and reduces free fatty acid (FFA) release from adipocytes by inhibiting lipolysis. Apelin also increases fatty acid oxidation in skeletal muscle and myocardium, reducing the rate of incomplete oxidation of long-chain acylcarnitines associated with insulin. In addition, apelin may prevent the development of obesity and atherosclerosis by reducing the release of free fatty acids and increasing perilipin content around lipid vesicles, and prevents fatty deposits in the blood vessels and plaque formation. Water metabolism: the expression of apelin/APJ in magnocellular neurons of the hypothalamus and periventricular organelles suggests that it may be involved in the regulation of body fluid balance. Apelin and its receptor APJ are expressed in all regions of human and rat kidneys, regulating body fluid homeostasis at the kidney level.