The purpose of this study is to determine whether a lipid infusion can up-regulate toll-like receptor 4 (TLR4) signaling in human subjects
The investigators plan to examine the effect of a lipid infusion on TLR4 expression and insulin sensitivity. A group of 30 subjects aged 18-60 years old, lean (BMI \< 26 kg/m2) normal glucose tolerant subjects without a family history of type 2 diabetes will receive a lipid or saline infusion. The subjects will be randomly assigned to first receive either a 48 hour long lipid or saline infusion. Approximately 4-6 weeks later subjects will return to undergo another study (if, in the first study they received lipid, on the second study they will receive saline, and vice versa). A near-equal number of women and men will be included in each group.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
12
30 ml/h for 48 h
30 ml/h for 48 h
Audie L. Murphy VA Hospital
San Antonio, Texas, United States
Muscle Insulin Sensitivity-M Value
Forty eight hrs after lipid or saline infusion, muscle insulin sensitivity will be measured by insulin clamp. The results are compared to determine whether lipid infusion reduces muscle insulin sensitivity compared to saline infusion.. The M value is defined as the exogenous glucose infusion rate at steady state (i.e, when the exogenous glucose infusion rate is equal to the rate of whole body glucose disposal).
Time frame: 48 hr after lipid/saline infusion
TLR4 Messenger Ribonucleic Acid (mRNA) in Muscle
Forty eight hrs after lipid or saline infusion, muscle TLR4 mRNA levels will be measured by RT-PCR. The results are compared to determine whether lipid infusion increases muscle TLR4 mRNA expression compared to saline infusion. Saline mean was used to normalize the data for both arms.
Time frame: 48 hr following lipid/saline infusion, pre-clamp
Extracellular Signal-regulated Kinase (ERK) Phosphorylation in Muscle
Forty eight hrs after lipid or saline infusion, muscle ERK phosphorylation will be measured by western blot. The results are compared to determine whether lipid infusion increases muscle ERK phosphorylation compared to saline infusion. Saline mean was used to normalize the data for both arms.
Time frame: 48 hr following lipid or saline infusion, pre-clamp
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