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
DOI: 10.2337/db11-0578
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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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.