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

Abstract

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.