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The Effects of Insulin, Glucose, and Pyruvate on the Kinetics of Leptin Secretion

Section of Endocrinology and Metabolism, McGuire Veterans Administration Medical Center (J.R.L.), and Medical College of Virginia/Virginia Commonwealth University (J.R.L.), Richmond, Virginia 23249

Leptin is a hormone that is secreted by fat cells and has roles in body weight regulation, glucose metabolism, reproduction, and other neuroendocrine functions. The purpose of this study was to determine whether the secretagogues, insulin, glucose, and pyruvate, enhance leptin secretion by increasing leptin synthesis, or whether these secretagogues stimulate the quantal release of a stored cytosolic pool of leptin. We found that in the absence of secretagogues, the rate of leptin secretion from isolated rat adipocytes approximately equals the rate of leptin synthesis. For 60 min after the addition of secretagogues, leptin synthesis rapidly increases, with little or no leptin secretion; leptin increases intracellularly by approximately 60% (P < 0.05). After 60 min, leptin is significantly released from cells. At 120 and 240 min, secretagogues enhance leptin secretion into the medium by 35% (P < 0.05) and 40% (P < 0.01), respectively. Cycloheximide prevents the synthesis and the secretagogue-mediated secretion of leptin. Monensin, an inhibitor of protein translocation, has no effect on leptin synthesis, but it blocks the secretagogue-mediated secretion of leptin. These findings suggest that secretagogues enhance leptin release by increasing leptin synthesis, rather than by enhancing the release of a preexisting cytosolic pool of leptin.