LKB1 Regulates Pancreatic β Cell Size, Polarity, and Function
LKB1 Regulates Pancreatic β Cell Size, Polarity, and Function
Pancreatic beta cells, organized in the islets of Langerhans, sense glucose and secrete appropriate amounts of insulin. We have studied the roles of LKB1, a conserved kinase implicated in the control of cell polarity and energy metabolism, in adult beta cells. LKB1-deficient beta cells show a dramatic increase in insulin secretion in vivo. Histologically, LKB1-deficient beta cells have striking alterations in the localization of the nucleus and cilia relative to blood vessels, suggesting a shift from hepatocyte-like to columnar polarity. Additionally, LKB1 deficiency causes a 65% increase in beta cell volume. We show that distinct targets of LKB1 mediate these effects. LKB1 controls beta cell size, but not polarity, via the mTOR pathway. Conversely, the precise position of the beta cell nucleus, but not cell size, is controlled by the LKB1 target Par1b. Insulin secretion and content are restricted by LKB1, at least in part, via AMPK. These results expose a molecular mechanism, orchestrated by LKB1, for the coordinated maintenance of beta cell size, form, and function.
- Harvard University United States
- Hebrew University of Jerusalem Israel
- WASHINGTON UNIVERSITY
- Harvard Medical School United States
- Washington University in St. Louis United States
Blood Glucose, Physiology, TOR Serine-Threonine Kinases, Adenylate Kinase, HUMDISEASE, Cell Polarity, Mice, Transgenic, Cell Biology, AMP-Activated Protein Kinases, Protein Serine-Threonine Kinases, Mice, Phosphatidylinositol 3-Kinases, Phosphotransferases (Alcohol Group Acceptor), Insulin-Secreting Cells, Insulin Secretion, Animals, Insulin, Carrier Proteins, Molecular Biology, Cells, Cultured, Signal Transduction
Blood Glucose, Physiology, TOR Serine-Threonine Kinases, Adenylate Kinase, HUMDISEASE, Cell Polarity, Mice, Transgenic, Cell Biology, AMP-Activated Protein Kinases, Protein Serine-Threonine Kinases, Mice, Phosphatidylinositol 3-Kinases, Phosphotransferases (Alcohol Group Acceptor), Insulin-Secreting Cells, Insulin Secretion, Animals, Insulin, Carrier Proteins, Molecular Biology, Cells, Cultured, Signal Transduction
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