Study of Dapagliflozin on Mitochondrial Dysfunction and Impaired Insulin Signaling/Action
Information source: The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Insulin Sensitivity; Multiple Mitochondrial Dysfunctions Syndrome
Intervention: Dapagliflozin (Drug); Placebo (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: The University of Texas Health Science Center at San Antonio Official(s) and/or principal investigator(s): Ralph DeFronzo, MD, Principal Investigator, Affiliation: The University of Texas Health Science Center at San Antonio
Overall contact: Aurora Merovci, Phone: 210-567 4686
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].
Clinical Details
Official title: 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
Study design: Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science
Primary outcome: Change in Insulin Sensitivity
Secondary outcome: Change in Mitochondrial Function
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 70 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- T2DM
- Drug Naive Or On Oral Therapy
Exclusion Criteria:
- Insulin Treatment
- Major Organ Disease
Locations and Contacts
Aurora Merovci, Phone: 210-567 4686
Diabetes Division, UTHSCSA, San Antonio, Texas 78229, United States; Recruiting Irma, Phone: 210-567-4686
Additional Information
Starting date: March 2011
Last updated: June 10, 2015
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