Journal article

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

N Konstantopoulos, JC Molero, SL McGee, B Spolding, T Connor, M De Vries, S Wanyonyi, R Fahey, S Morrison, C Swinton, S Jones, A Cooper, L Garcia-Guerra, VC Foletta, G Krippner, S Andrikopoulos, KR Walder

Diabetes | AMER DIABETES ASSOC | Published : 2012

Abstract

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 HbA 1c 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-bo..

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University of Melbourne Researchers

Grants

Funding Acknowledgements

Funding for this work was provided by a research grant from Verva Pharmaceuticals. S.L.M. is supported by the Diabetes Australia Research Trust Viertel Award. L.G.-G. was a recipient of Research Training Programme Fellowship from the Ministry of Science and Innovation of Spain.