To determine whether acutely-induced supraphysiological hyperinsulinemia influences brain metabolism in patients with type 1 diabetes (D) and healthy controls (C) as detected by MR Spectroscopy. Group D consisted of 4 patients with the average duration of diabetes for 7 years. They were matched according to age, sex and BMI to 4 healthy controls. 1H MR Spectroscopy was performed with a 1.5 Tesla. Spectra were obtained from parietooccipital white matter repeatedly during a 3-h hyperinsulinemic euglycemic clamp with 2 mU.kg-1.min-1. In group D, significantly lower basal concentrations of N-acetylaspartate (p=0.02), choline (p=0.03), creatine (p=0.002) and inositol (p=0.007) were detected compared to C. After the induction of hyperinsulinemia, concentrations of choline, creatine, GABA, inositol, lactate, NAA and composite signal glutamate + glutamine (Glx) stayed stable. The detection of glucose signal is less realiable at 1.5 Tesla but we registered the alteration in glucose concentration (p=0.003) in the whole group. Originally sightly elevated glucose concentration in D decreased on the contrary to the increase of originally lower glucose level in C. In conclusions, brain metabolism was altered in D. Short term supraphysiological euglycemic hyperinsulinemia induced changes in the concentration of brain glucose in both C and D., S. Kratochvílová, A. Škoch, M. Dezortová, E. Švehlíková, M. Hill, J. Brunová, M. Hájek, T. Pelikánová., and Obsahuje bibliografii
Lipoprotein lipase (LPL) is a key factor determining the clearance of triglycerides from the circulation. The enzyme activity is tissue-specifically regulated by insulin, but it is not clear yet how insulin regulates the total LPL activity in the circulation. To answer such question, we measured LPL activity using the intravenous fat tolerance test (IVFTT) that was carried out 1 h before as well as 2 h and 4 h after oral administration of glucose (75 g) in eleven healthy male volunteers. In control experiments, no glucose was given to the subjects. Glucose administration resulted in an expected increase in plasma glucose and insulin and in a suppression of non-esterified fatty acid concentration. The LPL activity assessed in IVFTT as a k2 rate constant did not change in control experiments and decreased to 78 % and 73 % of baseline values 2 h and 4 h after glucose administration, respectively (p=0.01). Similarly, LPL activity measured in the plasma after intravenous injection of heparin at the end of the experiments was 16 % lower (p<0.05) after glucose administration. In conclusion, LPL activity is already downregulated in vivo 2 h after glucose administration. The results of our study indicate that repeated IVFTT is a promising approach for studying acute changes in LPL activity., E. Jindřichová, S. Kratochvílová, J. Kovář., and Obsahuje bibliografii a bibliografické odkazy
The hyperinsulinemic euglycemic clamp (HEC) combined with indirect calorimetry (IC) is used for estimation of insulin-stimulated substrate utilization. Calculations are based on urinary urea nitrogen excretion (UE), which is influenced by correct urine collection. The aims of our study were to improve the timing of urine collection during the clamp and to test the effect of insulin on UE in patients with type 1 diabetes (DM1; n=11) and healthy subjects (C; n=11). Urine samples were collected (a) over 24 h divided into 3-h periods and (b) before and during two-step clamp (1 and 10 mIU.kg-1.min-1; period 1 and period 2) combined with IC. The UE during the clamp was corrected for changes in urea pool size (UEc). There were no significant differences in 24-h UE between C and DM1 and no circadian variation in UE in either group. During the clamp, serum urea decreased significantly in both groups (p<0.01). Therefore, UEc was significantly lower as compared to UE not adjusted for changes in urea pool size both in C (p<0.001) and DM1 (p<0.001). While UE did not change during the clamp, UEc decreased significantly in both groups (p<0.01). UEc during the clamp was significantly higher in DM1 compared to C both in period 1 (p<0.05) and period 2 (p<0.01). The UE over 24 h and UEc during the clamp were statistically different in both C and DM1. We conclude that urine collection performed during the clamp with UE adjusted for changes in urea pool size is the most suitable technique for measuring substrate utilization during the clamp both in DM1 and C. Urine collections during the clamp cannot be replaced either by 24-h sampling (periods I-VII) or by a single 24-h urine collection. Attenuated insulin-induced decrease in UEc in DM1 implicates the impaired insulin effect on proteolysis. and Obsahuje bibliografii a bibliografické odkazy