Comparative effects of short-term and long-term insulin-induced hypoglycemia on glucose production in the perfused livers of weaned rats

The liver glucose production (lgp) levels of 15-h overnight fasted weaned rats submitted to short-term insulin-induced hypoglycemia (st-iih) and long-term iih (lt-iih) were compared. experiments to characterize st-iih or lt-iih that followed an intraperitoneal (ip) injection (1.0 u/kg) of regular (st-iih) or insulin detemir (lt-iih) were performed and glycemia were measured 0 (normoglycemic control),0.5 h (st-iih),4 h and 6 h (lt-iih) later. the values of glycemia (mg/dl) were 77.8 ± 7.2 (normoglycemic control),26.2 ± 6.1 (st iih 0.5 h),21.2 ± 7.6 (lt-iih 4 h) and 35.3 ± 14.5 (lt-iih 6.0). the lgp levels were measured in the rats submitted to st-iih (0.5 h) and lt-iih (4 h or 6 h). the rats that received ip saline were used as the normoglycemic control group (cog). the livers from the cog and iih groups (st-iih or lt-iih) were perfused in situ with infusion of l-alanine (5 mm),l-glutamine (10 mm),glutamine dipeptide (5 mm),l-lactate (2 mm) or glycerol (2 mm). the st-iih rats showed a higher lgp level than cog group following the l-glutamine infusion (p < 0.05),but the lgp levels that were measured following the l-lactate,l-alanine,glutamine dipeptide (5 mm),l-lactate (2 mm) or glycerol infusion remained unchanged. moreover,if the period of iih was expanded to 4 h following insulin injection,the lgp levels induced by l-alanine,glutamine dipeptide or glycerol infusion also increased (p < 0.05,lt-iih vs. cog). however,the lgp from the l-lactate infusion remained unchanged until 6 h after insulin injection. in conclusion,these results suggest that the intensification of liver gluconeogenesis during st-iih and lt-iih in weaned rats is not a synchronous all or nothing process; instead,this process integrated in a temporal manner and is specific for each gluconeogenic substrate. copyright © 2011 by institute of pharmacology polish academy of sciences.