Fig. 3. Caerulein-induced pancreatitis is more severe in PACIRKO vs IR^lox/lox mice.

Pancreatitis was induced in control double floxed insulin receptor (IR^lox/lox) mice vs Pancreatic Acinar Conditional Insulin Receptor Knock Out (PACIRKO) mice that lack insulin receptors (IRs) by caerulein (Caer; 50 µg/Kg × 8 hourly IP injections over 2 days) or phosphate-buffered saline (PBS) as a control and blood/tissue was harvested 2 and 24 h after the last injection. Multiple readouts of pancreatitis include; pancreatic tissue oedema (wet/dry weight ratio, a), cytokine expression (qPCR of tissue mRNA; TNFα, b; IL-6, c, IL-1β, d; and the housekeeping 18 S rRNA, e), histological signs of injury (haematoxylin and eosin (H&E), f, g, j and k), immunohistochemistry of the inflammatory marker, CD45 (brown) (h, i, l and m). n–q Histology injury scores (where 3 is the most severe) for oedema (n), inflammatory cell infiltration (o), necrosis (p), and total score (q; sum of other scores). Group sizes were: 2 h harvest, IR^lox/lox PBS, n = 6; IR^lox/lox Caer, n = 6; PACIRKO PBS, n = 5; PACIRKO Caer, n = 6; 24 h harvest, IR^lox/lox PBS, n = 5; IR^lox/lox Caer, n = 5; PACIRKO PBS, n = 6; PACIRKO Caer, n = 6. Significance (exact p values as indicated) was determined by one-way ANOVA with Sidak’s multiple comparisons. Data are presented as mean value ± SEM.