Insulin stimulates ammoniagenesis in canine renal proximal tubular segments

To characterize the effect of insulin on ammoniagenesis in renal proximal tubule, ammonia productions were measured in suspensions of canine renal proximal tubular segments incubated with 10 mM L-glutamine and varying concentrations of insulin. Productions of ammonia were linear functions of time for 120 min. Insulin (10(-6) M) increased ammonia production at 2 h by 34 +/- 5%. At the same time, gluconeogenesis, as measured by glucose production, was decreased by 16 +/- 2%. Significant enhancement of ammoniagenesis occurred in suspensions of segments incubated with as little as 10(-9) M insulin. Half-maximal stimulation occurred at between 10(-9) and 10(-8) M insulin. Oxidation of L-glutamine in cells within segments was also increased by insulin in a concentration-dependent manner. Insulin increased ammonia productions in segments incubated at pH 7.5 but not at 7.0. Under the former conditions, insulin enhanced ammoniagenesis in proximal tubular segments under conditions such that extracellular [Na+] was greater than intracellular [Na+], but not when extracellular [Na+] equaled intracellular [Na+]. We conclude that insulin stimulates ammonia production in suspensions of canine renal proximal tubular segments. Stimulation of ammonia production in vitro could reflect an action of insulin to enhance proximal tubular ammoniagenesis in vivo.