Methazolamide is a new hepatic insulin sensitizer that lowers blood glucose in vivo

Konstantopoulos, Nicky, Molero, Juan C., McGee, Sean L., Spolding, Briana, Connor, Tim, de Vries, Melissa, Wanyonyi, Stephen, Fahey, Richard, Morrison, Shona, Swinton, Coutney, Jones, Sharon, Cooper, Adrian, Garcia-Guerra, Lucia, Foletta, Victoria C., Krippner, Guy, Andrikopoulos, Sofianos and Walder, Ken R. 2012, Methazolamide is a new hepatic insulin sensitizer that lowers blood glucose in vivo, Diabetes, vol. 61, no. 8, pp. 2146-2154, doi: 10.2337/db11-0578.

Attached Files
Name Description MIMEType Size Downloads

Title Methazolamide is a new hepatic insulin sensitizer that lowers blood glucose in vivo
Author(s) Konstantopoulos, Nicky
Molero, Juan C.
McGee, Sean L.ORCID iD for McGee, Sean L.
Spolding, Briana
Connor, Tim
de Vries, Melissa
Wanyonyi, Stephen
Fahey, Richard
Morrison, Shona
Swinton, Coutney
Jones, Sharon
Cooper, Adrian
Garcia-Guerra, Lucia
Foletta, Victoria C.ORCID iD for Foletta, Victoria C.
Krippner, Guy
Andrikopoulos, Sofianos
Walder, Ken R.ORCID iD for Walder, Ken R.
Journal name Diabetes
Volume number 61
Issue number 8
Start page 2146
End page 2154
Total pages 9
Publisher American Diabetes Association
Place of publication Alexandria, Va.
Publication date 2012-08
ISSN 0012-1797
Summary We previously used Gene Expression Signature technology to identify methazolamide (MTZ) and related compounds with insulin sensitizing activity in vitro. The effects of these compounds were investigated in diabetic db/db mice, insulin-resistant diet-induced obese (DIO) mice, and rats with streptozotocin (STZ)-induced diabetes. MTZ reduced fasting blood glucose and HbA1c levels in db/db mice, improved glucose tolerance in DIO mice, and enhanced the glucose-lowering effects of exogenous insulin administration in rats with STZ-induced diabetes. Hyperinsulinemic-euglycemic clamps in DIO mice revealed that MTZ increased glucose infusion rate and suppressed endogenous glucose production. Whole-body or cellular oxygen consumption rate was not altered, suggesting MTZ may inhibit glucose production by different mechanism(s) to metformin. In support of this, MTZ enhanced the glucose-lowering effects of metformin in db/db mice. MTZ is known to be a carbonic anhydrase inhibitor (CAI); however, CAIs acetazolamide, ethoxyzolamide, dichlorphenamide, chlorthalidone, and furosemide were not effective in vivo. Our results demonstrate that MTZ acts as an insulin sensitizer that suppresses hepatic glucose production in vivo. The antidiabetic effect of MTZ does not appear to be a function of its known activity as a CAI. The additive glucose-lowering effect of MTZ together with metformin highlights the potential utility for the management of type 2 diabetes.
Language eng
DOI 10.2337/db11-0578
Field of Research 110103 Medical Biochemistry: Inorganic Elements and Compounds
Socio Economic Objective 920104 Diabetes
HERDC Research category C1 Refereed article in a scholarly journal
Grant ID NHMRC 1030474
Copyright notice ©2012, American Diabetes Association
Persistent URL

Document type: Journal Article
Collection: School of Medicine
Connect to link resolver
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 16 times in TR Web of Science
Scopus Citation Count Cited 16 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 327 Abstract Views, 3 File Downloads  -  Detailed Statistics
Created: Tue, 21 Aug 2012, 10:45:06 EST by Jane Moschetti

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact