TABLE 2

Arterial levels and net hepatic balances of plasma NEFAs, 3-hydroxybutyrate, glycerol, lactate, and alanine before and after oral administration of BAY R 3401 in the presence of non-insulin-induced hypoglycemia with and without mild hyperinsulinemia and in the presence of the maintenance of euglycemia with and without mild hyperinsulinemia in 18-h-fasted conscious dogs

GroupControl periodBAY R 3401 with or without peripheral glucose infusion (min)
1020306090120180
NEFA
 Hypoglycemia
  Plasma level (mmol/l)0.67 ± 0.040.68 ± 0.070.80 ± 0.07*0.92 ± 0.14*1.29 ± 0.23*1.39 ± 0.20*1.49 ± 0.15*1.52 ± 0.09*
  NHB (μmol · kg−1 · min−1)−2.51 ± 0.32−2.51 ± 0.26−2.85 ± 0.26−3.22 ± 0.37*−4.43 ± 0.90*−5.32 ± 0.71*−6.12 ± 0.74*−6.69 ± 1.05*
 Hypoglycemia + insulin
  Plasma level (mmol/l)0.82 ± 0.080.72 ± 0.090.53 ± 0.090.64 ± 0.100.73 ± 0.140.73 ± 0.140.79 ± 0.100.77 ± 0.164
  NHB (μmol · kg−1 · min−1)−3.18 ± 0.56−3.27 ± 0.40−1.95 ± 0.40−2.39 ± 0.20−3.20 ± 1.02−3.47 ± 0.54−2.90 ± 0.19−2.06 ± 0.61
 Euglycemia
  Plasma level (mmol/l)0.79 ± 0.090.73 ± 0.080.81 ± 0.080.80 ± 0.100.84 ± 0.130.78 ± 0.120.82 ± 0.060.91 ± 0.06
  NHB (μmol · kg−1 · min−1)−1.83 ± 0.29−1.51 ± 0.35−1.43 ± 0.33−1.96 ± 0.33−2.06 ± 0.51−2.18 ± 0.39−2.32 ± 0.25−2.39 ± 0.24
 Euglycemia + insulin
  Plasma level (mmol/l)0.65 ± 0.090.68 ± 0.090.56 ± 0.090.48 ± 0.080.34 ± 0.06*0.31 ± 0.05*0.33 ± 0.06*0.29 ± 0.06*
  NHB (μmol · kg−1 · min−1)−1.65 ± 0.22−1.92 ± 0.27−1.44 ± 0.30−0.86 ± 0.24−0.71 ± 0.19*−0.48 ± 0.18*−0.73 ± 0.23*−0.58 ± 0.17*
3-Hydroxybutyrate
 Hypoglycemia
  Blood level (μmol/l)20 ± 319 ± 215 ± 216 ± 328 ± 449 ± 4*65 ± 7*111 ± 20*
  NHB (μmol · kg−1 · min−1)0.72 ± 0.140.64 ± 0.120.76 ± 0.120.66 ± 0.111.17 ± 0.171.93 ± 0.21*2.52 ± 0.47*3.91 ± 1.25*
 Hypoglycemia + insulin
  Blood level (μmol/l)29 ± 821 ± 319 ± 314 ± 332 ± 1532 ± 1525 ± 924 ± 8
  NHB (μmol · kg−1 · min−1)1.41 ± 0.450.75 ± 0.170.82 ± 0.170.87 ± 0.192.02 ± 0.891.69 ± 0.831.30 ± 0.621.86 ± 1.04
 Euglycemia
  Blood level (μmol/l)33 ± 1124 ± 627 ± 632 ± 324 ± 314 ± 1*17 ± 431 ± 15
  NHB (μmol · kg−1 · min−1)1.06 ± 0.380.60 ± 0.10.94 ± 0.11.01 ± 0.081.10 ± 0.060.61 ± 0.050.90 ± 0.151.00 ± 0.33
 Euglycemia + insulin
  Blood level (μmol/l)19 ± 321 ± 314 ± 313 ± 35 ± 1*4 ± 1*6 ± 1*4 ± 2*
  NHB (μmol · kg−1 · min−1)0.60 ± 0.080.49 ± 0.040.54 ± 0.060.40 ± 0.030.27 ± 0.07*0.24 ± 0.03*0.23 ± 0.08*0.15 ± 0.07*
Glycerol
 Hypoglycemia
  Blood level (μmol/l)63 ± 466 ± 577 ± 5*98 ± 12*107 ± 15*107 ± 12*119 ± 5*124 ± 11*
  NHB (μmol · kg−1 · min−1)−1.12 ± 0.11−1.11 ± 0.11−1.63 ± 0.11*−2.34 ± 0.56*−2.39 ± 0.51*−2.31 ± 0.43*−2.68 ± 0.27*−2.91 ± 0.50*
 Hypoglycemia + insulin
  Blood level (μmol/l)88 ± 1068 ± 957 ± 978 ± 692 ± 1888 ± 6105 ± 10108 ± 9
  NHB (μmol · kg−1 · min−1)−2.20 ± 0.28−1.42 ± 0.21−1.49 ± 0.21−2.06 ± 0.34−2.60 ± 0.65−2.36 ± 0.28−2.88 ± 0.46−3.34 ± 0.61
 Euglycemia
  Blood level (μmol/l)85 ± 574 ± 798 ± 773 ± 1096 ± 792 ± 1270 ± 878 ± 13
  NHB (μmol · kg−1 · min−1)−1.41 ± 0.14−1.29 ± 0.15−1.26 ± 0.15−1.35 ± 0.17−1.68 ± 0.10−1.63 ± 0.16−1.49 ± 0.19−1.45 ± 0.21
 Euglycemia + insulin
  Blood level (μmol/l)68 ± 751 ± 749 ± 845 ± 6*38 ± 7*36 ± 7*43 ± 7*53 ± 9*
  NHB (μmol · kg−1 · min−1)−1.08 ± 0.20−0.78 ± 0.20−0.79 ± 0.19−0.61 ± 0.10−0.56 ± 0.04*−0.52 ± 0.07*−0.59 ± 0.13*−0.78 ± 0.18*
Lactate
 Hypoglycemia
  Blood level (μmol/l)632 ± 113595 ± 65522 ± 65573 ± 53479 ± 56461 ± 44*467 ± 54*452 ± 42*
  NHB (μmol · kg−1 · min−1)−1.18 ± 2.76−2.08 ± 2.67−2.44 ± 2.67−4.21 ± 1.78−4.37 ± 0.83*−5.80 ± 1.39*−7.62 ± 1.24*−8.73 ± 1.36*
 Hypoglycemia + insulin
  Blood level (μmol/l)716 ± 147630 ± 129616 ± 129542 ± 109464 ± 112506 ± 129619 ± 136548 ± 52
  NHB (μmol · kg−1 · min−1)−2.09 ± 1.71−2.23 ± 1.19−3.84 ± 1.19−5.82 ± 2.76*−5.45 ± 2.44*−4.80 ± 1.32*−6.56 ± 1.97*−8.48 ± 2.22*
 Euglycemia
  Blood level (μmol/l)636 ± 81647 ± 124615 ± 124536 ± 98564 ± 91548 ± 69469 ± 71*430 ± 73*
  NHB (μmol · kg−1 · min−1)−3.05 ± 2.69−1.27 ± 4.15−3.71 ± 4.15−3.40 ± 3.56−1.02 ± 2.23−2.44 ± 0.89−4.20 ± 0.27−5.47 ± 0.42
 Euglycemia + insulin
  Blood level (μmol/l)775 ± 120700 ± 120650 ± 80560 ± 60450 ± 40*370 ± 20*370 ± 30*420 ± 40*
  NHB (μmol · kg−1 · min−1)7.73 ± 4.552.51 ± 5.100.29 ± 3.241.99 ± 2.090.32 ± 1.09*−0.96 ± 0.92*−0.91 ± 0.56*−1.87 ± 0.57*
Alanine
 Hypoglycemia
  Blood level (μmol/l)317 ± 21312 ± 21301 ± 21292 ± 13270 ± 29227 ± 27*206 ± 26*161 ± 26*
  NHB (μmol · kg−1 · min−1)−1.99 ± 0.21−1.67 ± 0.23−2.37 ± 0.23−2.71 ± 0.22*−2.97 ± 0.52*−2.73 ± 0.36*−2.97 ± 0.47*−2.74 ± 0.54*
 Hypoglycemia + insulin
  Blood level (μmol/l)340 ± 29325 ± 33312 ± 33310 ± 40254 ± 36*217 ± 30*198 ± 27*172 ± 17*
  NHB (μmol · kg−1 · min−1)−2.75 ± 0.37−2.98 ± 0.58−2.79 ± 0.59−3.38 ± 0.70−3.23 ± 0.88−3.05 ± 0.73−2.87 ± 0.60−2.90 ± 0.52
 Euglycemia
  Blood level (μmol/l)299 ± 25290 ± 25257 ± 25253 ± 28246 ± 25245 ± 27232 ± 35*204 ± 34*
  NHB (μmol · kg−1 · min−1)−2.31 ± 0.32−2.12 ± 0.46−1.94 ± 0.46−2.33 ± 0.34−1.85 ± 0.27−2.02 ± 0.51−2.20 ± 0.37−1.99 ± 0.63
 Euglycemia + insulin
  Blood level (μmol/l)390 ± 45370 ± 50370 ± 50330 ± 40290 ± 30*210 ± 20*190 ± 20*170 ± 20*
  NHB (μmol · kg−1 · min−1)−1.93 ± 0.39−2.23 ± 0.39−2.22 ± 0.41−2.04 ± 0.25−2.29 ± 0.43−1.73 ± 0.26−1.67 ± 0.20−1.65 ± 0.24
  • Data for each group are means ± SE from five dogs.

  • *

    * Significantly changed from the values during the control period in the same group. Positive and negative values in net hepatic balance (NHB) represent output and uptake rates, respectively.