Document Detail


Possible role of carbonic anhydrase in rat pancreatic islets: enzymatic, secretory, metabolic, ionic, and electrical aspects.
MedLine Citation:
PMID:  17284575     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The presence of carbonic anhydrase (type V) was recently documented in rat and mouse pancreatic islet beta-cells by immunostaining and Western blotting. In the present study, the activity of carbonic anhydrase was measured in rat islet homogenates and shown to be about four times lower than in rat parotid cells. The pattern for the inhibitory action of acetazolamide on carbonic anhydrase activity also differed in islet and parotid cell homogenates, suggesting the presence of different isoenzymes. NaN3 inhibited carbonic anhydrase activity in islet homogenates and both D-[U-14C]glucose oxidation and glucose-stimulated insulin secretion. Acetazolamide (0.3-10.0 mM) also decreased glucose-induced insulin output but failed to affect adversely D-[U-14C]glucose oxidation, although it inhibited the conversion of D-[5-3H]glucose to [3H]OH and that of D-[U-14C]glucose to acidic metabolites. Hydrochlorothiazide (3.0-10.0 mM), which also caused a concentration-related inhibition of the secretory response, like acetazolamide (5.0-10.0 mM), decreased H(14)CO3- production from D-[U-14C]glucose (16.7 mM). Acetazolamide (5.0 mM) did not affect the activity of volume-sensitive anion channels in beta-cells but lowered intracellular pH and adversely affected both the bioelectrical response to d-glucose and its effect on the cytosolic concentration of Ca2+ in these cells. The lowering of cellular pH by acetazolamide, which could well be due to inhibition of carbonic anhydrase, might in turn account for inhibition of glycolysis. The perturbation of stimulus-secretion coupling in the beta-cells exposed to acetazolamide may thus involve impaired circulation in the pyruvate-malate shuttle, altered mitochondrial Ca2+ accumulation, and perturbation of Cl- fluxes, resulting in both decreased bioelectrical activity and insulin release.
Authors:
Abdullah Sener; Hassan Jijakli; Saleh Zahedi Asl; Philippe Courtois; Allen P Yates; Sylvain Meuris; Leonard C Best; Willy J Malaisse
Related Documents :
8257685 - Mass spectrometric characterization of arachidonate-containing plasmalogens in human pa...
8993395 - Signal transduction of pacap and glp-1 in pancreatic beta cells.
17827405 - Mechanisms of low-glucose sensitivity in carotid body glomus cells.
2581295 - Modification of the function of cardiac subcellular organelles by insulin.
2992665 - Insensitivity of calcium-dependent endothelial stimulation in rat isolated aorta to the...
9016805 - Cftr-like chloride channels in non-ciliated bronchiolar epithelial (clara) cells.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-02-06
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  292     ISSN:  0193-1849     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-06-05     Completed Date:  2007-07-30     Revised Date:  2008-05-05    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E1624-30     Citation Subset:  IM    
Affiliation:
Laboratory of Experimental Hormonology, Brussels Free University, Brussels, Belgium. abdsener@ulb.ac.be
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Acetazolamide / pharmacology
Animals
Bicarbonates / metabolism
Carbonic Anhydrase Inhibitors / pharmacology
Carbonic Anhydrases / metabolism,  physiology*
Electrophysiology
Female
Glucose / metabolism
Hydrogen-Ion Concentration
Insulin / secretion*
Intracellular Fluid / metabolism
Islets of Langerhans / enzymology,  metabolism,  physiology*
Male
Parotid Gland / cytology,  metabolism
Rats
Rats, Wistar
Sodium Azide / pharmacology
Chemical
Reg. No./Substance:
0/Bicarbonates; 0/Carbonic Anhydrase Inhibitors; 11061-68-0/Insulin; 26628-22-8/Sodium Azide; 50-99-7/Glucose; 59-66-5/Acetazolamide; EC 4.2.1.1/Carbonic Anhydrases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Endothelin-1 and pancreatic islet vasculature: studies in vivo and on isolated, vascularly perfused ...
Next Document:  Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochon...