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Role of Bumetanide on Insulin Secretion

Almutairi, Mohammed Mashari
http://rave.ohiolink.edu/etdc/view?acc_num=wright1408377608

Abstract Details

2014, Master of Science (MS), Wright State University, Pharmacology and Toxicology.
Insulin secretion depends on the electrical properties of the ß-cells in pancreatic islets. The consensus mechanism of insulin secretion involves glucose-stimulated metabolic increase in the ATP/ADP ratio. This increase closes ATP-sensitive K+ (KATP) channels resulting in ß-cell plasma membrane depolarization, which in turn activates voltage-dependent Ca2+ channels further resulting in Ca2+ influx and release of insulin stored in granules. In addition to this well-known consensus mechanism, insulin secretion also depends on electrogenic efflux of Cl- ions. The Na+K 2Cl- cotransporters (NKCCs) maintain the intracellular concentration of Cl- ([Cl-]i) at values higher than those predicted at thermodynamic equilibrium. This distribution of Cl-makes possible the electrogenic exit of the anion from ß-cells upon opening of volume-regulated anion channels (VRAC). Therefore, the prevailing notion states that disruption of the ß-cell Cl- gradient by inhibition of NKCCs with loop diuretics such as furosemide or bumetanide (BTD) impairs insulin secretion. Our results challenge that long-standing concept by demonstrating that long-term BTD does not impair insulin secretion in mouse ß-cells in vitro and that this effect is related to changes in the NKCC expression pattern and Cl-uptake in response to the diuretic.
Mauricio Di Fulvio, Ph.D. (Advisor)
Norma Adragna, Ph.D. (Committee Member)
David Cool, Ph.D. (Committee Member)
87 p.
Medicine; Pharmacology
pharmacology; medicine

Recommended Citations

Citations

  • Almutairi, M. M. (2014). Role of Bumetanide on Insulin Secretion [Master's thesis, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1408377608

    APA Style (7th edition)

  • Almutairi, Mohammed. Role of Bumetanide on Insulin Secretion . 2014. Wright State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=wright1408377608.

    MLA Style (8th edition)

  • Almutairi, Mohammed. "Role of Bumetanide on Insulin Secretion ." Master's thesis, Wright State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=wright1408377608

    Chicago Manual of Style (17th edition)

wright1408377608
416
© 2014, some rights reserved.Creative Commons License Role of Bumetanide on Insulin Secretion by Mohammed Mashari Almutairi is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Wright State University and OhioLINK.