Investigation of glycemia recovery with oral administration of glycerol, pyruvate, and L-lactate during long-term, insulin-induced hypoglycemia.

AIM: The acute effect of oral administration of isolated or combined glycerol, pyruvate, and L-lactate on glycemia recovery (GR) during long-term, insulin-induced hypoglycemia (IIH) was compared. METHODS: Glycemia of 24 h-fasted rats that received intraperitoneal injection (1.0 U/kg) of regular insulin (IIH group) or saline (COG group) and, 15, 150, or 165 min later, oral saline (control IIH), glycerol (100 mg/kg), pyruvate (100 mg/kg), L-lactate (100 mg/kg), or combined glycerol+pyruvate+L-lactate (each 33.3 or 100 mg/kg) was compared. In addition, for comparative purposes, a group that received glucose (100 mg/kg) was included. Glycemia was measured 180 min after insulin or saline injection. To investigate the participation of the hepatic availability of gluconeogenic substrates to GR, livers from IIH and COG rats that received physiological or supraphysiological concentrations of isolated or combined glycerol, pyruvate, and L-lactate were compared. Liver experiments were done 180 min after insulin or saline injection. RESULTS: Oral glycerol, pyruvate, and L-lactate (isolated or combined) or glucose promoted GR. Moreover, the best GR was obtained with combined glycerol+pyruvate+L-lactate (100 mg/kg). In agreement, livers that received supraphysiological concentrations of glycerol, pyruvate, and L-lactate (isolated or combined) showed higher glucose release than livers that received physiological concentrations of these substances (isolated or combined). CONCLUSION: The best GR obtained with combined administration of glycerol, pyruvate, and L-lactate (100 mg/kg) during long-term IIH was a consequence of the higher liver availability of these substances associated with a maintained liver ability to produce glucose from gluconeogenic substrates.

Glycemia recovery with oral amino acid administration during experimental short-term insulin-induced hypoglycemia.

AIM: The acute effects of the oral administration of L-alanine (L-ala), L-glutamine (L-gln), L-ala+L-gln, and L-alanyl-L-glutamine (AGP) on glycemia recovery during short-term insulin-induced hypoglycemia (IIH) were compared. METHODS: For this purpose, the blood glucose levels of 24-h-fasted rats that received intraperitoneal injections of regular insulin (IIH group) or saline [control (COG) group] and, 15 min later, oral administration of L-ala (100 mg/kg), L-gln (100 mg/kg), L-ala (50 mg/kg)+L-gln (50 mg/kg), or AGP (100 mg/kg) were compared. Liver perfusion experiments and blood collection to measure blood glucose levels were performed 30 min after insulin (1.0 U/kg) or saline injection. Livers from the IIH and COG groups were perfused with saturating concentrations of L-ala, L-gln, L-ala+L-gln, or AGP, and the maximal hepatic production of glucose, urea, ammonia, L-lactate, and pyruvate was evaluated. RESULTS: In contrast with L-gln, L-ala+L-gln, or AGP, the oral administration of L-ala promoted glycemia recovery. In agreement with these results, livers from IIH rats showed maximal hepatic production of glucose and urea from L-ala with 50% of the amount used to obtain the maximal hepatic production of glucose and urea in livers from COG rats. In contrast with L-gln, L-ala+L-gln, or AGP, the maximal hepatic production of urea from L-ala occurred in the absence of ammonia accumulation. CONCLUSION: The results indicate that the best glycemia recovery promoted by the oral administration of L-ala was a consequence of the higher efficiency of the livers from IIH rats in producing glucose from L-ala.