Action of acetazolamide on liver pyruvate carboxylase activity, glycogenolysis and gluconeogenesis of mice

Cao, Thanh Phuong; Rous, Simonne

doi:10.1016/0020-711x(78)90121-0

Cited by 14 publications

(4 citation statements)

References 14 publications

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“…Acetazolamide and ethoxyzolamide were found to inhibit gluconeogenesis in vitro or after acute administration in rats (30,35,36). In vivo studies found that acetazolamide caused acidosis and insulin resistance in alloxanized diabetic dogs (37), and decreased glucose tolerance while increasing insulin levels in fed (but not fasted) mice for 24 h postacetazolamide injection (38).…”

Section: Discussionmentioning

confidence: 99%

Methazolamide Is a New Hepatic Insulin Sensitizer That Lowers Blood Glucose In Vivo

Konstantopoulos

Molero²,

McGee³

et al. 2012

Diabetes

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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.

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Section: Discussionmentioning

confidence: 99%

Methazolamide Is a New Hepatic Insulin Sensitizer That Lowers Blood Glucose In Vivo

Konstantopoulos

Molero²,

McGee³

et al. 2012

Diabetes

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show abstract

“…Previously Acetazolamide and Ethoxyzolamide were found to inhibit gluconeogenesis in vitro or after acute administration in rats. [18][19][20] our studies indicate that Acetazolamide treatment in STZ induced diabetic rats' lowers glucose production and increases glycolytic production of lactate. We found (Table 2) 6.9 fold increase in blood lactate level when compared with normal control and 3.0 fold increases in blood lactate level when compared with untreated diabetic group.…”

Section: Carbonic Anhydrase Inhibition (With Acetazolamide) Increasesmentioning

confidence: 84%

Inhibition of Carbonic Anhydrase Results in Blood Lactate Accumulation (BLA) in STZ Induced Diabetic Rats

Ismail¹,

Ameh²,

Amodu³

et al. 2015

J Diabetes Metab

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Carbonic anhydrase is a pH regulatory enzyme, whose inhibition leads to metabolic acidosis. We investigated whether carbonic anhydrase inhibition may be associated with blood lactate accumulation in Streptozotocin (STZ) induced diabetic rats. The study aimed to provide a new marker to assist in identifying diabetic individuals at a high risk of developing lactic acidosis. Erythrocyte carbonic anhydrase activity with 4-nitrophenyl acetate as substrates was investigated in (STZ) induced diabetic rats. STZ induced diabetic rats showed significant increase in erythrocyte carbonic anhydrase (CA) activity of 9.7 ± 0.7 μMol/min/μL and blood lactate level of 6.2 ± 1.2 mMol/L when compared with Non Diabetic group CA enzyme activity of 5.5 ± 0.6 μMol/min/μL and blood lactate level of 3.9 ± 0.5 mMol/L. Inhibition of erythrocyte carbonic anhydrase activity with Acetazolamide results in 6.9 fold increase in blood lactate level when compared with Non diabetic group. Therefore inhibition of Carbonic anhydrase in STZ induced diabetic rats' result in blood lactate accumulation and reduced blood glucose concentration.

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“…Previous published studies have provided mixed results regarding the potential of carbonic anhydrase inhibitors to modulate blood glucose levels. Acetazolamide and ethoxyzolamide were found to inhibit gluconeogenesis in vitro or after acute administration in rats [28][29][30]. [28] concluded that carbonic anhydrase is functionally important for gluconeogenesis in the male guinea pig liver when there is a requirement for bicarbonate as substrate.…”

Section: Discussionmentioning

confidence: 99%

Carbonic Anhydrase: A New Therapeutic Target for Managing Diabetes

Ismail¹,

Amodu²

2016

J Metabolic Synd

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Action of acetazolamide on liver pyruvate carboxylase activity, glycogenolysis and gluconeogenesis of mice

Cited by 14 publications

References 14 publications

Methazolamide Is a New Hepatic Insulin Sensitizer That Lowers Blood Glucose In Vivo

Methazolamide Is a New Hepatic Insulin Sensitizer That Lowers Blood Glucose In Vivo

Inhibition of Carbonic Anhydrase Results in Blood Lactate Accumulation (BLA) in STZ Induced Diabetic Rats

Carbonic Anhydrase: A New Therapeutic Target for Managing Diabetes

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