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vehicle
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50
0
-30
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0
30
60
90
120
15. Recently, the preparation of 4-benzyl-4-aminopiperidines by the Ellman
reaction was reported with the use of excess Grignard reagent in moderate
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Time (min)
Drug Glucose
p.o. p.o.
Figure 2. Effect of 12u in OGTT in ICR mice.
which was stable during in vitro human CYP metabolism, reduced
the blood glucose excursion in OGTT. Further optimization of the
derivatives is now being investigated.
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18. An extract from Caco-2 was used as the source of DPP-IV in the assay. The cell
extract was prepared from cells solubilized in lysis buffer (10 mM, Tris–HCl
(pH 8.0), 0.15 M NaCl, 0.04 U aprotinin, 0.50% nonidet-P40) that were then
centrifuged at 18,500g for 1 h at 4 °C to remove the cell debris. The assay was
References and notes
conducted by adding 5
volume of 135 L in an assay buffer (25 mM Tris–HCl (pH 7.4), 0.14 M NaCl,
10 mM KCl, 1% (w/v) BSA) to 96-well flat-bottom plates. The reaction was
initiated by adding 15 L of 0.4 mM substrate (Ala-Pro-AFC). The reaction was
run for 20 min at 37 °C, and then 10 L of 25% acetic acid was added to stop the
reaction. Fluorescence was measured using Fusion (excitation 380 nm;
lg of solubilized Caco-2 protein, diluted to a final
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l
l
l
a
emission 485 nm). The test compounds and solvent controls were added to
the assay buffer.
19. Xu, J.; Ok, H. O.; Gonzalez, E. J.; Colwell, L. F., Jr.; Habulihaz, B.; He, H.; Leiting,
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21. Male SD rats (7–8 weeks of age) were starved overnight. The rats were
orally administered a vehicle (distilled water, 5 mL/kg) or 12u (1, 3, 10 mg/
kg; 5 mL/kg); then, blood samples were taken from the jugular vein at
intervals of 30 min, 2 h, and 4 h after treatment. Plasma samples were
centrifuged at 1400g for 10 min at 4 C. The assay was conducted by adding
20
initiated by adding 20
200 mM Hepes, 0.2 mg/mL BSA, pH 7.5). The reaction was run for 15 min at
room temperature and then 6 L of 25% acetic acid was added to stop the
reaction. Fluorescence was measured using Fusion (excitation 380 nm;
l
L
of rat plasma to 96-well flat-bottom plates. The reaction was
l
L
of 0.4 mM substrate (Ala-Pro-AFC, diluted in
l
a
emission 485 nm). Male ICR mice (6 weeks of age) were starved
overnight.
22. The mice were orally administered a vehicle (distilled water, 10 mL/kg) or 12u
(30 mg/kg; 10 mL/kg). The blood glucose concentration was determined by a
glucometer from blood taken from a nick in the tail, 30 min after the treatment.
The mice were then orally challenged with glucose (2 g/kg; 10 mL/kg). The
blood glucose levels were determined from tail bleeds taken at intervals of 20,
40, 60, and 120 min after the glucose challenge.