Acidotic pH augments glucagon secretion and gluconeogenesis in the isolated perfused rat pancreas and liver

To study effects of acidosis on glucagon secretion and gluconeogenetic action of glucagon, rat pancreas and liver were perfused with media of pH 6.4, 6.9, 7.4 and 7.9. Glucagon secretion from the pancreas during glucopenic perfusion (1 mmol/l) was blunted at alkalotic pH, and was augmented at acidotic pH; 0.28+/- 0.18 at pH 7.9 (P<0.01), 3.57+/-0.94 at pH 6.9 (P<0.01) and 1.72+/- 0.36 at pH 6.4 (P<0.01), vs. 0.66 +/- 0.25 pmol for 15 min at pH 7.4. Incorporation rate of C-14 of lactate-U-C-14 into glucose carbon one was decreased at pH 7.9 (1.2+/-0.2% for 15 min, P<0.05) and was increased at pH 6.9 (2.8+/-0.5%, P<0.05) compared to that at pH 7.4 (1.9+/-0.3%). Percent increasing rate of lactate gluconeogenesis by 1 nmol/l glucagon was not different within a range of pH 6.4-7.9. Thus, glucagon-stimulated gluconeogenesis from lactate was smaller at pH 7.9 (2.2+/-0.6%) and was significantly greater at pH 6.9 (4.9+/-0.9%, P<0.05) than that at pH 7.4 (3.2+/-0.6%). These results suggest that the pancreatic glucagon secretion and the glucagon-stimulated hepatic gluconeogenesis play more important roles in the maintainance of blood glucose level in the stress states associated with acidosis than without acidosis.