Articles by Neali A. Armstrong in JoVE
En hög halt Zhengshan Zhao1, Yassan Abdolazimi1, Neali A. Armstrong1, Justin P. Annes1 1Department of Medicine, Division of Endocrinology, Stanford University School of Medicine Kritiska utmaningar för diabetesforskningen fältet är att förstå de molekylära mekanismer som reglerar ö β-cellreplikation och för att utveckla metoder för att stimulera β-cellförnyelsen. Häri en hög halt screening metod för att identifiera och bedöma β-cellreplikation främjande aktivitet av små molekyler presenteras.
Other articles by Neali A. Armstrong on PubMed
Repurposing CAMP-modulating Medications to Promote β-cell Replication Molecular Endocrinology (Baltimore, Md.). Oct, 2014 | Pubmed ID: 25083741 Loss of β-cell mass is a cardinal feature of diabetes. Consequently, developing medications to promote β-cell regeneration is a priority. cAMP is an intracellular second messenger that modulates β-cell replication. We investigated whether medications that increase cAMP stability or synthesis selectively stimulate β-cell growth. To identify cAMP-stabilizing medications that promote β-cell replication, we performed high-content screening of a phosphodiesterase (PDE) inhibitor library. PDE3, -4, and -10 inhibitors, including dipyridamole, were found to promote β-cell replication in an adenosine receptor-dependent manner. Dipyridamole's action is specific for β-cells and not α-cells. Next we demonstrated that norepinephrine (NE), a physiologic suppressor of cAMP synthesis in β-cells, impairs β-cell replication via activation of α(2)-adrenergic receptors. Accordingly, mirtazapine, an α(2)-adrenergic receptor antagonist and antidepressant, prevents NE-dependent suppression of β-cell replication. Interestingly, NE's growth-suppressive effect is modulated by endogenously expressed catecholamine-inactivating enzymes (catechol-O-methyltransferase and l-monoamine oxidase) and is dominant over the growth-promoting effects of PDE inhibitors. Treatment with dipyridamole and/or mirtazapine promote β-cell replication in mice, and treatment with dipyridamole is associated with reduced glucose levels in humans. This work provides new mechanistic insights into cAMP-dependent growth regulation of β-cells and highlights the potential of commonly prescribed medications to influence β-cell growth.