SAD-A and AMPK kinases: The “yin and yang” regulators of mTORC1 signaling in pancreatic β cells

Abstract

SAD-A kinase is a member of the AMPK-related family of kinases, which are under the control of LKB1 kinase. In the human kinome, SAD-A is most closely related to AMPK, a key energy sensor and master regulator of metabolism. In contrast to AMPK, little is known about the physiological function of the SAD-A kinase in metabolism. Recent studies using knockout mice have revealed a striking role of the SAD-A kinase in regulating dynamic functions of islet β cells, from glucose-stimulated insulin secretion (GSIS), islet β-cell size and mass, to GLP-1 response as the first tissue-specific effector of mTORC1 signaling. These studies suggest that SAD-A and AMPK kinase may function as the positive and negative regulators of mTORC1 signaling in islet β cells. Importantly, these findings have implicated SAD-A kinase as a novel drug target for the treatment of type 2 diabetes.

Keywords::

• insulin secretion
• type 2 diabetes
• LKB1
• AMPK-related kinase
• GLP‑1
• incretin