Insulin Resistance
Conditions
Keywords
FFA, insulin resistance, mitochondria
Brief summary
This study aims to explore time-dependent effects of lipid infusion an intramyocellular lipid metabolites and the induction of impaired insulin signaling.
Detailed description
Increased availability of free fatty acids impairs glucose disposal in young healthy humans. Patients with type 2 diabetes have reduced whole body glucose disposal, increased ectopic lipid deposition in skeletal muscle and the liver and impaired mitochondrial function. Recent studies suggest that lipid metabolites such as diacylglycerol (DAG), ceramides and long-chain acyl-coA represent the active mediators inducing insulin resistance. Possible targets are DAG-sensitive Proteinkinase C (PKC θ, PKC ε) which inhibit the insulin signaling cascade and ceramides which interfere with the insulin signaling cascade at Proteinkinase B/AKT. Prior studies raised controvesial evidence, thus, it is yet unclear, whether DAG or ceramides are the primary agents inducig lipid-induced insulin resistance. Therefore, the current study aims to explore the time course of the appearance of intramyocellular lipid compunds during lipid infusion in parallel assessing markers of impaired insulin action.
Interventions
DIETARY_SUPPLEMENTLipovenös lipid infusion
Lipid enriched infusions will be applied for 2-6 hours.
Sponsors
Heinrich-Heine University, Duesseldorf
German Diabetes Center
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
20 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* non-diabetic (OGTT), no family history of diabetes, BMI\<30 kg/m2, age: 20-55 years, no medication For the athletes group additionally: * VO2max \> 60ml/kg/min for males and VO2max \> 45ml/kg/min for females Active in endurance-exercise activities, 3 times a week for at least 2 years Stable level of training for at least 3 months
Exclusion criteria
* acute illness within the last 2 weeks, autoimmune diseases, renal insufficiency (creatinine\> 1.5 mg/dl), cardiovascular diseases, anemia (Hb\< 12g/l), donation of blood within the last 4 weeks before the study, thyroid diseases, pregnancy, smoking, night-shift working (disturbed circadian rhythm), defective coagulation or wound healing, cancer, allergy against soja products
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| intramyocellular lipid metabolites | after 4 hours lipid infusion | Muscle biopsies are taken before, after 2.5 and 4 hours of lipid infusion |
| muscle glucose flux | during lipid infusion | glycogen synthesis rate, glucose-6-phosphate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| insulin resistance of glucose uptake and mitochondrial function | after 4 hours lipid infusion | Mitochondrial function will bes assessed from muscle biopsy samples taken after 4 hours, insulin sensitivity will be assessed from hyperinsulinemic-euglycemic clamps following 4 hours lipid infusion |
Countries
Germany
Outcome results
None listed