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

Diabetes
Nicky KonstantopoulosKen R Walder

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-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 eff...Continue Reading

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Citations

Mar 13, 2014·Expert Opinion on Drug Safety·Erik R Swenson
Feb 24, 2016·Trends in Pharmacological Sciences·Nigel TurnerJi-Ming Ye
Feb 26, 2015·BioMed Research International·Peng-Tao XuZhi-Bin Yu
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Jun 30, 2021·Diabetes & Metabolic Syndrome·Sweta MohantySwati Swayamsiddha

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Methods Mentioned

BETA
ELISA
Assay
PCR

Software Mentioned

Statistical Package for the Social Sciences SPSS
Gene Expression Signature [

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