Faculty Collaboration Database

Expression of carbonic anhydrase V in pancreatic beta cells suggests role for mitochondrial carbonic anhydrase in insulin secretion. J Biol Chem 1998 Sep 18;273(38):24620-3

Date

09/12/1998

Pubmed ID

9733757

DOI

10.1074/jbc.273.38.24620

Scopus ID

2-s2.0-0032544429 (requires institutional sign-in at Scopus site)   68 Citations

Abstract

Carbonic anhydrase V (CA-V) is a mitochondrial enzyme that provides bicarbonate for pyruvate carboxylase in liver and kidney. In the course of a survey of the tissue distribution of CA-V, we detected intense immunostaining in pancreatic islets when sections from rat and mouse pancreases were reacted with a polyclonal antibody to recombinant mouse CA-V. The distribution and large number of CA-V-positive cells in each islet suggested that they represented beta cells. Double immunofluorescence staining of tissue sections and isolated islet cells showed cellular colocalization of CA-V and insulin, confirming that beta cells contain CA-V. Western blotting of rat islets of Langerhans and primary beta cells showed 33- and 30-kDa polypeptides of precursor and mature CA-V, respectively. The CA-V expression was beta cell-specific since no CA-V immunoreaction was detected in the primary alpha cells. Immunohistochemical staining for CA-I, CA-II, CA-IV, CA-VI, and CA-IX was negative in beta cells, and Western blotting of beta cells also failed to identify any CA in beta cells except CA-V. The specific localization of CA-V in beta cells led us to hypothesize that CA-V may be functionally linked to the regulation of insulin secretion. Consistent with this hypothesis, the CA inhibitor acetazolamide was found to be a strong inhibitor of glucose-stimulated insulin secretion by isolated rat pancreatic islets.

Author List

Parkkila AK, Scarim AL, Parkkila S, Waheed A, Corbett JA, Sly WS

Author

John A. Corbett PhD Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acetazolamide
Animals
Carbonic Anhydrases
Enzyme Precursors
Glucose
Immunohistochemistry
In Vitro Techniques
Insulin
Islets of Langerhans
Isoenzymes
Mice
Microscopy, Confocal
Mitochondria
Rats
Rats, Sprague-Dawley