Fat Induced Insulin Resistance and Atherosclerosis
Completed · Not applicable
Conditions studied: Other Fatty Acid Oxidation Disorders, Diabetes Mellitus, Insulin Resistance
In brief
The overall objective of the current proposal is to strengthen the putative link between FFA induced insulin resistance and atherosclerotic vascular disease (ASVD). To this end, the investigators will test the following hypotheses: 1) that FFA induced activation of protein kinase C βII (PKC β II) and δ and other serine kinases such as IκB kinase (IKK) in human muscle is associated with a decrease in insulin stimulated tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1) and of IRS-1 associated phosphatidylinositol 3 (PI3) kinase; 2) that these changes precede the development of insulin resistance; 3) that the decrease in IκB-α results in activation of nuclear factor κB (NFκB) and the expression of adhesion molecules and cytokines; 4) that PKC and IKK are involved in producing insulin resistance and activation of the IκB/ NFκB pathway and lastly 5) that the same mechanisms operative in healthy volunteers are also operative in patients with T2DM.The investigators will test these hypotheses in normal (current) and diabetic volunteers (previously completed) . Euglycemic-hyperinsulinemic clamps will be performed with and without co-infusion of lipid plus heparin (to raise FFAs) and by obtaining serial muscle and fat biopsies and blood samples will be obtained for measurement of substrates, hormones, enzymes and metabolites.
Key facts
- Study ID
- NCT02348190
- Run by
- Temple University
- People needed
- 86
- Starts
- 2003-06-01
- Expected to finish
- 2015-06-01
- Last updated by the study team
- 2015-11-25
Who can join
Age: 18 and older, up to 75. Sex: any. Healthy volunteers: accepted.
You may qualify if…
- The investigators plan to study 32 healthy normal subjects.
- These volunteers will be male and female, between the ages of 30 and 75 years and of all races.
- None of these volunteers will have a family history of diabetes or any other endocrine disorder and none will be taking any medications.
You may not qualify if…
- Patients with chronic health problems including cardiovascular, pulmonary, hematologic (*Hb< 9 g/dl), renal (serum creatinine > 1.8 mg/dl), hepatic disease, AIDS or other chronic infectious disease will be excluded.
- Pregnant women will be excluded. Non-pregnant women will be studied during the follicular phase of their menstrual cycle. If needed, a pregnancy test will be performed to exclude pregnancy.
Where it is running
- Temple University Hospital — Philadelphia, Pennsylvania, United States
Full record on ClinicalTrials.gov
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