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This Article Full Text Full Text (PDF) All Versions of this Article: 292/6/E1624    most recent 00631.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sener, A. Articles by Malaisse, W. J. Search for Related Content PubMed PubMed Citation Articles by Sener, A. Articles by Malaisse, W. J.

Possible role of carbonic anhydrase in rat pancreatic islets: enzymatic, secretory, metabolic, ionic, and electrical aspects

¹Laboratory of Experimental Hormonology, Brussels Free University, Brussels, Belgium; and ²Departments of Clinical Biochemistry and Medicine, University of Manchester, Manchester, United Kingdom

Submitted 21 November 2006 ; accepted in final form 30 January 2007

The presence of carbonic anhydrase (type V) was recently documented in rat and mouse pancreatic islet -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 H¹⁴CO₃^– production from D-[U-¹⁴C]glucose (16.7 mM). Acetazolamide (5.0 mM) did not affect the activity of volume-sensitive anion channels in -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 -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.

acetazolamide; D-glucose metabolism; insulin secretion; bioelectrical activity; bicarbonate production