Lipid-induced Insulin Resistance
Conditions
Keywords
Insulin resistance, vascular impairment, diabetes
Brief summary
There is a current debate whether impaired insulin-mediated microvascular perfusion limits the delivery of hormones and nutrients to muscle and whether short term FFA elevation affects transcapillary transport of insulin and glucose thereby representing a rate-controlling step for insulin-stimulated muscular glucose disposal in humans. To address these questions, the investigators determined the changes of interstitial glucose and insulin in skeletal muscle of healthy volunteers during intravenous administration of triglycerides or glycerol under physiologic and supraphysiologic hyperinsulinemic conditions.
Detailed description
Increased lipid availability reduces insulin-stimulated glucose disposal in skeletal muscle, which is generally explained by lipid induced inhibition of myocellular insulin signalling, It remains unclear whether lipids also impair transcapillary transport of insulin and glucose which could thereby become rate-controlling for glucose disposal Increased accumulation and availability of lipids cause impaired skeletal muscle insulin sensitivity. It is yet unclear if transcapillary transport of insulin and glucose is impaired by acute elevation of free fatty acids and represents a rate-limiting step during the development of short-term lipid-induced insulin resistance. We determined the changes of interstitial glucose and insulin in skeletal muscle of healthy volunteers during intravenous administration of triglycerides and heparin or glycerol under physiologic and supraphysiologic hyperinsulinemic conditions.
Interventions
OTHERElevation of FFA during OGTT
0-240 min: Intralipid® 20%, Pharmacia AB, Stockholm, Sweden, 90 ml/hr; Heparin Immuno®, Immuno AG, Vienna, Austria, bolus: 200IU, continuous infusion: 0.2 IU.kg-1.min-1
OTHERElevation of FFA during Clamp
0-240 min: Intralipid® 20%, Pharmacia AB, Stockholm, Sweden, 90 ml/hr; Heparin Immuno®, Immuno AG, Vienna, Austria, bolus: 200IU, continuous infusion: 0.2 IU.kg-1.min-1.
Sponsors
Medical University of Vienna
German Diabetes Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
20 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* The volunteers have to be older than 19 years, * nonobese (body mass index, BMI less than 27 kg/m2), * normolipidemic (fasting serum concentration of triglycerides \< 140 mg/dL and * total cholesterol \< 200 mg/dL) and * non-smokers.
Exclusion criteria
* The following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood flow | between the start of the lipid/glycerol infusion until the end of the study (360 min) | Regional blood flow. Muscular blood flow will be measured by the laser Doppler flow technique (LDF, Moor Instruments, Devon, UK) as described previously |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Interstitial insulin concentration | between the start of the lipid/glycerol infusion until the end of the study (360 min) | Interstitial insulin concentration in skeletal muscle is measured via microdialysis based on sampling of analytes from the interstitial space fluid by means of a dialysis membrane at the tip of a microdialysis probe. |
Countries
Austria
Outcome results
None listed