Fat and Transcapillary Insulin Transport

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.

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 exclusion criteria will be applied:

• any medication within two weeks prior to the start of study,
• regular alcohol consumption > 40 g/d,
• acute inflammatory disease defined by serum C-reactive protein > 1 mg/dL,
• abnormalities in the screening visit or in laboratory tests considered as clinically relevant,
• family history of diabetes mellitus or dyslipidemia,
• glucose intolerance,
• allergy or hypersensitivity against study medication,
• blood clotting disorders.