NCT01439854

Study of Dapagliflozin on Mitochondrial Dysfunction and Impaired Insulin Signaling/Action

Regulation of Hepatic and Peripheral Glucose Metabolism: Protocol IVA. Effect of Plasma Glucose Reduction by Selective SLGT2 Inhibition on Mitochondrial Dysfunction and Impaired Insulin Signaling/Sensitivity in T2DM

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: The University of Texas Health Science Center at San Antonio · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to examine the effect of the chronic treatment of type 2 diabetes (T2DM) with dapagliflozin on: (1) mitochondrial gene function/expression and insulin signaling/action and (2) oral glucose tolerance and beta cell function. Dapagliflozin is a potent, highly specific inhibitor of renal glucose transport \[SGLT2\].

Detailed description

"Glucotoxicity" has been implicated as a cause of insulin resistance and impaired beta cell function in T2DM. Abundant support for the glucotoxicity hypothesis has been provided by in vivo and in vitro studies in animals, but a rigorous test of this hypothesis in man is lacking. The investigators propose to test the glucotoxicity hypothesis by chronically reducing the plasma glucose in type 2 diabetic subjects (T2DM) with an inhibitor of renal glucose transport, dapaglifozin, and examining the effect of restoration of normoglycemia on mitochondrial function and insulin signaling/sensitivity. Lastly, the investigators will test the "glucolipotoxicity" hypothesis, which states that the toxic effects of elevated plasma FFA on insulin sensitive tissues (i.e., muscle) are magnified in the presence of concurrent hyperglycemia. Thus, high glucose levels increase malonyl CoA, which inhibits CPT I, leading to accumulation of FACoA/DAG, which impair mitochondrial function and inhibit insulin action.

Conditions

• Insulin Sensitivity
• Multiple Mitochondrial Dysfunctions Syndrome

Interventions

Type	Name	Description
DRUG	Dapagliflozin	Treatment arm, 10 mg per day for 2 weeks
DRUG	Placebo	Patients are treated with placebo

Timeline

• Start date: 2011-03-01
• Primary completion: 2018-06-30
• Completion: 2018-06-30
• First posted: 2011-09-23
• Last updated: 2025-07-03
• Results posted: 2019-10-29

Locations

1 site across 1 country: United States