Leptin promotes K ATP channel trafficking by AMPK signaling in pancreatic β-cells

• DOI: 10.1073/pnas.1216351110
• Publication Date: 2013-07-16T01:07:37Z
• Authors: Sun-Hyun Park; Shin-Young Ryu; Weon-Jin Yu; Young Eun Han; Young-Sun Ji; Keunhee Oh; Jong-Woo Sohn; Ajin Lim; Jae-Pyo Jeon; Hyunsu Lee; Kyu-Hee Lee; Suk-Ho Lee; Per-Olof Berggren; Ju-Hong Jeon; Won-Kyung Ho
• Keywords: AMP-Activated Protein Kinase; Sulfonylurea receptor; Leptin receptor

Leptin is a pivotal regulator of energy and glucose homeostasis, defects in leptin signaling result obesity diabetes. The ATP-sensitive potassium (K(ATP)) channels couple metabolism to insulin secretion pancreatic β-cells. In this study, we provide evidence that modulates β-cell functions by promoting K(ATP) channel translocation the plasma membrane via AMP-activated protein kinase (AMPK) signaling. were localized mostly intracellular compartments β-cells fed state translocated fasted state. This process was defective leptin-deficient ob/ob mice, but restored treatment. We discovered molecular mechanism leptin-induced AMPK activation involves canonical transient receptor potential 4 calcium/calmodulin-dependent β. dependent on both concentrations, so at optimal concentrations leptin, activated sufficiently induce trafficking hyperpolarization physiological range fasting levels. There close correlation between phospho-AMPK levels potentials, suggesting AMPK-dependent key for regulating potentials. Our results present pathway whereby regulates homeostasis modulating excitability.