The effect of different doses of dimethylbiguanide (DMB) on liver blood flow, Blood glucose and plasma immunoreactive insulin in anaesthetized rats

Abstract The effect of different doses of dimethylbiguanide (DMB) administered by the i.v. and i.d. route on liver blood flow, blood glucose and plasma immunoreactive insulin was investigated in anaesthetized rats. Liver blood flow was measured by thermocouples implanted into the liver utilising Grayson's principle of “internal calorimetry”. In addition blood glucose and immunoreactive insulin in the plasma was measured at different time intervals following the different doses of DMB. Intraarterial BP was monitored during the whole experiment. Following 100 mg/kg DMB i.v. a significant increase in liver blood flow, blood glucose, plasma immunoreactive insulin and BP was observed. 50 mg/kg DMB i.v. did not affect any of the parameters measured, while 150 mg/kg DMB was already a toxic dose. After i.d. administration no changes were seen following a dose of 175 mg/kg DMB and 1500 mg/kg DMB was already toxic. 500 mg/kg, however, showed a similar significant increase in liver blood flow, blood glucose, plasma immunoreactive insulin and BP was observed. 50 mg/kg effects observed could be suppressed by a simultaneous administration of 1 mg/kg propranolol i.v. In addition a decrease in liver blood flow occurred which is explained by a direct effect of the β-adrenergic blocking agent propranolol on the liver vasculature. Therefore a selective β-adrenergic effect of the biguanides seems a likely explanation for the increased liver blood flow following DMB administration. Administering 1.6 g/kg glucose i.d. an increase in liver blood flow, blood glucose and plasma immunoreactive insulin was observed. This influence on blood glucose and plasma immunoreactive insulin was inhibited by simultaneous administration of 1.6 g/kg glucose and 500 mg/kg DMB, while liver blood flow showed the same increase when glucose alone was given. After changing the experimental design in giving the 500 mg/kg DMB i.d. and 30 min later 1.6 g/kg glucose a much higher increase in liver blood flow occurred, which might reflect an additive effect.