Hypothesis 1. To define whether stimulation of ATGL and suppression of G0/G1 switch gene occur in the initial phases of diabetic ketoacidosis and thus can be identified as the primary mechanisms behind this life threatening condition. 2. Make a human model for studying ketoacidosis. The investigators plan to reduce in their regular insulin over night. In the morning we administer endotoxin, which together with a relative lack of insulin will initiate ketogenesis - a state of ketoacidosis. On another occasion strict glycemic control is imposed by means of intravenous insulin. The testing is done two separate days with at least 3 weeks in between and patients are admitted to hospital the evening before the day of testing. The investigators use isotopic tracers to determine metabolic fluxes and analyse fat (ATGL, G0/G1 switch gene) and muscle biopsies.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
9
LPS is endotoxin from gram negative bacteria. It is used scientifically to mimic infection lasting 4-8 hours.
Aarhus University Hospital
Aarhus, Denmark
Insulin signaling expressed as a CHANGE in phosphorylation of intracellular target proteins and CHANGE in mRNA expression of target genes in muscle- and fat-tissue.
Change in phosphorylation of target proteins and messenger RNA (mRNA) expression of target genes assessed with western blotting technique.
Time frame: Muscle and fat biopsies obtained on each study day (arm): t1= 6.45 (-75min) am t2=11.15 (195min) am t3= 12.30 pm (270min)
Change in Intracellular markers of lipid metabolism in muscle- and fat tissue biopsies
Muscle and fat at t1 and t2. Muscle biopsy at t3. Intracellular markers are assessed by western blotting.
Time frame: Muscle and fat biopsies obtained on each study day (arm): t1= 6.45 am (-75min) t2=11.15 (195min) am t3= 12.30 pm (270min)
Metabolism
Change in glucose, fat and protein metabolism assessed by tracer kinetics on every study day (specific times below) and by indirect calorimetry. \[3H 3\]Glucose tracer from t=0 - 360min. Palmitic acid tracer from t=165min - 360min. Urea tracer from 0min - 240min. amino acid tracer from 60 min - 360 min.
Time frame: Change in glucose, fat and protein metabolism between study days and during each study day
Cytokines and stress hormones
Measurement of immune response to endotoxin and hypoinsulinaemia. Estimating the whole body stress during ketoacidosis and pre ketoacidosis.
Time frame: In basal period t=0-240 minutes and in clamp period t=240-390 minutes
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