Fig. 9: Caerulein infusion-induced increase in plasma amylase is reduced by insulin infusion with tight glycaemic control using the hyperinsulinaemic euglycaemic clamp.

C57BL/6 mice were catheterized via the carotid artery and jugular vein under recover anaesthesia to allow the continuous infusion of caerulein (to induce acute pancreatic injury), insulin (12 mU/kg/min) and glucose (variable rate) to maintain euglycaemia. Caerulein-induced acute pancreatic injury was experimentally induced by continuous infusion of caerulein (50 μg/kg/h) over 5 h and plasma amylase was assessed as an early and immediate readout of pancreatic injury during the course of the experiment (e) and at the end (f). Mice were separated into 4 groups of 6 mice receiving insulin alone (a), caerulein and insulin (b, insulin added 2 h into the caerulein infusion), caerulein alone (c) or saline control (d). For clarity, data are presented as mean ± SEM assessed every 10 min during the entire 5 h. The same data are presented as dot plots showing the full data distribution with lines connecting the mean in Fig. S10. The effect of different caerulein administration regimes were compared on plasma amylase at 0, 1 h, 3 h and 5 h (mean plasma amylase ± SEM from groups of 4 mice, e) including; bolus caerulein injection (via IV line) every hour (open square), low dose continuous caerulein infusion (10 μg/kg/h) and high dose continuous caerulein infusion (50 μg/kg/h). This higher dose continuous caerulein infusion (50 μg/kg/h) induced the maximum increase in plasma amylase at 5 h and was therefore used in combination with the hyperinsulinaemic euglycaemic clamp (b). Mean plasma amylase (±SEM) from 4 groups of 6 mice measured at 0 and 5 h in saline control, caerulein alone, caerulein with insulin infusion and insulin infusion alone (f). Significance (exact p values as indicated) was determined by one-way ANOVA with Sidak’s multiple comparisons.