It has been observed that subjects with obesity and insulin resistance have higher concentrations of branched chain amino acids in plasma or serum. However, this association has been established under fasting conditions, so they only give information about a metabolic state and do not reflect the dynamics and flexibility of the metabolism of these amino acids in the absence or presence of insulin resistance. The main aim of this study is to compare the catabolism of branched chain amino acids and their keto acids in subjects with and without insulin resistance, after the infusion of an amino acid solution with high concentration of the branched chain amino acids, leucine, valine, and isoleucine. The results of this project will allow the investigators to understand the dynamics of the branched chain amino acids and their derivatives, and its relationship with insulin resistance, which could eventually be used to design nutritional strategies to treat insulin resistance and thus, delay the development of type 2 diabetes.
An 8% crystalline L-amino acid solution with high concentrations of branched chain amino acids, leucine, isoleucine, and valine, will be administered intravenously. The dose will be calculated considering the 25% of the estimated protein per day. For example, if the patient is 70 kg and the investigators consider 1g/kg/day, the amount of protein to be administered will be 17.5 grams (70 x 0.25 = 17.5 grams). This dose will be placed in a short peripheral intravenous catheter and administered at a rate of 1.5ml per minute, using an infusion pump. The patient will be monitored all the time by a physician. After the administration of the L- amino acid solution, the investigators will take blood samples at 0, 15, 30, 45, 60, 90 and 120 minutes to determine the area under the curve for glucose, insulin, amino acids and branched chain keto acids.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
40
Intravenous administration of 8% crystalline L-amino acids with high concentrations of branched chain amino acids.
Instituto Nacional de Ciencias Medicas Y Nutricion Salvador Zubiran
México, Mexico
Area under the curve of branched-chain amino acids.
Time Frame: Measured for 0,15,30,45,60,90,120 minutes following the intravenous administration of the amino acid solution rich in branched chain amino acids. The branched chain amino acids concentration will be determined by liquid chromatography coupled to mass spectrometry (LC-MS/MS), and the area under the curve will be calculated using the trapezoidal rule.
Time frame: 2 hours
Area under the curve of branched-chain keto acids.
Time Frame: Measured for 0,15,30,45,60,90,120 minutes following the intravenous administration of the amino acid solution rich in branched chain amino acids. The branched chain keto acids concentration will be determined by liquid chromatography coupled to mass spectrometry (LC-MS/MS), and the area under the curve will be calculated using the trapezoidal rule.
Time frame: 2 hours
Area under the curve of insulin.
Time Frame: Measured for 0,15,30,45,60,90,120 minutes following the intravenous administration of the amino acid solution rich in branched chain amino acids. The insulin concentration will be determined using an ELISA assay and the area under the curve will be calculated using the trapezoidal rule.
Time frame: 2 hours
Area under the curve of glucose.
Time Frame: Measured for 0,15,30,45,60,90,120 minutes following the intravenous administration of the amino acid solution rich in branched chain amino acids. The glucose concentration will be determined using an enzymatic assay (Hexokinase) and the area under the curve will be calculated using the trapezoidal rule.
Time frame: 2 hours
Respiratory quotient.
Time Frame: Measured for 0,15,30,45,60,90,120 minutes following the intravenous administration of the amino acid solution rich in branched chain amino acids The respiratory quotient will be determined by indirect calorimetry and the area under the curve will be calculated using the trapezoidal rule.
Time frame: 2 hours
Expression of the enzyme branched-chain aminotransferase 2 (BCAT2)
Time Frame: Measured for 0, 60 and 120 minutes following the intravenous administration of the amino acid solution rich in branched chain amino acids. The expression of enzyme branched chain aminotransferase 2 (BCAT2) will be determined in mononuclear cells isolated from blood by Western Blot and quantitative PCR.
Time frame: 2 hours
Expression of the enzyme branched-chain keto acid dehydrogenase (BCKDH)
Time Frame: Measured for 0, 60 and 120 minutes following the intravenous administration of the amino acid solution rich in branched chain amino acids. The expression of enzyme branched chain ketoacid dehydrogenase (BCKDH) will be determined in mononuclear cells isolated from blood by Western Blot and quantitative PCR.
Time frame: 2 hours
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