The effect of phenyl ethyl biguanide in vivo and in vitro on gluconeogenesis and ammonia production in rats

The drug phenyl ethyl biguanide (PEBG) was used in vivo and in vitro to study further the relationship between renal gluconeogenesis and ammonia production in the rat. When PEBG was injected intraperitoneally into the rats, it caused a decrease in urinary ammonia in spite of a greater degree of systemic acidosis. PEBG injections also blocked the increase in glucose and ammonia production by renal cortical slices from rats which had been made acidotic by oral administration of ammonium chloride 2h previously. With increasing concentrations of PEBG in vitro, there was inhibition of gluconeogenesis and ammonia production from glutamine and glutamate as substrates. The two processes were equally inhibited when glutamate was used as substrate but with glutamine, gluconeogenesis was more inhiblted than ammonia production. The inhibition of renal gluconeogenesis by PEBG in vitro was similar when succinate, oxaloacetate, fructose, glutamine and glutamate were used as substrates. The results show that PEBG does not inhibit gluconeogenesis by blocking a specific site in the gluconeogenic pathway. In addition, further proof is provided of the physiological interrelationship of renal ammonia production and gluconeogenesis (Summary)

Diabetes -Current concepts (Part II of the Henderson prize essay of 1965)

When one looks back to 1922 when Banting and Best first discovered insulin, one cannot help but be impressed with the remarkable strides made towards an understaning of this complex disease. Research has extended from gene complex through the prediabetic concept to the final action of insulin on the tissues. To date however, nothing has been finally settled and we are probably no better off today than the time of Banting and Best (Summary)