Insulin is a hormone secreted by pancreatic B-cells in response to glucose stimulation. Proper insulin secretion keeps blood glucose in a physiological range by promoting the uptake of glucose by insulin-sensitive target tissues. In addition to glucose, various other metabolic and hormonal stimuli act on B-cells to modulate insulin secretion and maintain metabolic homeostasis. In this thesis, leptin is shown to induce a Ca2+ influx via Src kinase potentiation of N-Methyl-D-Aspartate (NMDA) receptors that initiates the CaMKK?-AMPK signaling pathways.