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TABLE 3

Hepatic gluconeogenic flux and net glycogenolysis before and after oral administration of BAY R 3401 in the presence of hypoglycemia or euglycemia with and without hyperinsulinemia in 18-h-fasted conscious dogs

GroupControl periodBAY R 3401 with or without peripheral glucose infusion (min)
1020306090120180
Gluconeogenic flux (μmol glucose · kg−1 · min−1        
 Hypoglycemia 3.11 ± 1.50 3.89 ± 1.39 4.39 ± 1.39 6.00 ± 0.89* 6.38 ± 0.61* 6.78 ± 1.39* 8.11 ± 1.11* 8.72 ± 1.22* 
 Hypoglycemia + insulin 4.90 ± 1.37 4.81 ± 1.28 5.46 ± 1.29 7.32 ± 2.25 7.26 ± 2.43 6.63 ± 1.53 7.59 ± 1.82 8.81 ± 1.94 
 Euglycemia 4.50 ± 1.11 3.38 ± 1.72 4.39 ± 1.78 4.72 ± 1.38 3.22 ± 1.50 4.88 ± 0.89 5.00 ± 0.61 5.50 ± 0.50 
 Euglycemia + insulin 2.47 ± 0.46 2.62 ± 0.49 2.62 ± 0.51 2.35 ± 0.30 2.57 ± 0.45 2.47 ± 0.76 2.42 ± 0.45 2.98 ± 0.62 
Net glycogenolytic rate (μmol glucose · kg−1 · min−1        
 Hypoglycemia 7.39 ± 0.78 7.05 ± 0.38 4.27 ± 0.38* 1.83 ± 1.83* 0.66 ± 0.39* 0.44 ± 0.78* 0.67 ± 1.22* 0.78 ± 1.22* 
 Hypoglycemia + insulin 7.49 ± 1.47 4.36 ± 1.09 2.26 ± 1.06* −1.10 ± 1.51* −3.54 ± 1.28* −2.96 ± 0.82* −4.76 ± 0.49* −6.87 ± 0.93* 
 Euglycemia 8.17 ± 1.50 7.78 ± 1.22 4.17 ± 0.28* 3.06 ± 0.72* −0.78 ± 1.22* −3.72 ± 0.56* −6.11 ± 1.39* −7.33 ± 1.44* 
 Euglycemia + insulin 13.74 ± 4.21 5.83 ± 4.84 2.31 ± 2.00* −0.29 ± 1.08* −5.91 ± 2.61* −4.86 ± 2.09* −4.81 ± 1.78* −6.48 ± 1.73* 
GroupControl periodBAY R 3401 with or without peripheral glucose infusion (min)
1020306090120180
Gluconeogenic flux (μmol glucose · kg−1 · min−1        
 Hypoglycemia 3.11 ± 1.50 3.89 ± 1.39 4.39 ± 1.39 6.00 ± 0.89* 6.38 ± 0.61* 6.78 ± 1.39* 8.11 ± 1.11* 8.72 ± 1.22* 
 Hypoglycemia + insulin 4.90 ± 1.37 4.81 ± 1.28 5.46 ± 1.29 7.32 ± 2.25 7.26 ± 2.43 6.63 ± 1.53 7.59 ± 1.82 8.81 ± 1.94 
 Euglycemia 4.50 ± 1.11 3.38 ± 1.72 4.39 ± 1.78 4.72 ± 1.38 3.22 ± 1.50 4.88 ± 0.89 5.00 ± 0.61 5.50 ± 0.50 
 Euglycemia + insulin 2.47 ± 0.46 2.62 ± 0.49 2.62 ± 0.51 2.35 ± 0.30 2.57 ± 0.45 2.47 ± 0.76 2.42 ± 0.45 2.98 ± 0.62 
Net glycogenolytic rate (μmol glucose · kg−1 · min−1        
 Hypoglycemia 7.39 ± 0.78 7.05 ± 0.38 4.27 ± 0.38* 1.83 ± 1.83* 0.66 ± 0.39* 0.44 ± 0.78* 0.67 ± 1.22* 0.78 ± 1.22* 
 Hypoglycemia + insulin 7.49 ± 1.47 4.36 ± 1.09 2.26 ± 1.06* −1.10 ± 1.51* −3.54 ± 1.28* −2.96 ± 0.82* −4.76 ± 0.49* −6.87 ± 0.93* 
 Euglycemia 8.17 ± 1.50 7.78 ± 1.22 4.17 ± 0.28* 3.06 ± 0.72* −0.78 ± 1.22* −3.72 ± 0.56* −6.11 ± 1.39* −7.33 ± 1.44* 
 Euglycemia + insulin 13.74 ± 4.21 5.83 ± 4.84 2.31 ± 2.00* −0.29 ± 1.08* −5.91 ± 2.61* −4.86 ± 2.09* −4.81 ± 1.78* −6.48 ± 1.73* 

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 represent output and uptake rates, respectively. Maximum gluconeogenic rates are the sum of the uptake rates of lactate, glycerol, and amino acids. The glycogenolytic rates are obtained by subtracting the maximum gluconeogenic rate from the sum of NHGO, lactate production, and glucose oxidation.

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