Diabetes aggravates acute pancreatitis and inhibits pancreas regeneration in mice.
OBJECTIVE
It is well established that acute pancreatitis often causes diabetes and that a high blood glucose level associated with pancreatitis is a marker of poor prognosis. The aim of this study was to evaluate if diabetes merely reflects the severity of pancreatitis or whether it can also aggravate the progression of this disease in a vicious circle.


METHODS
Reversible acute oedematous pancreatitis was induced in untreated and streptozotocin-treated diabetic mice by injection of cerulein. Progression of pancreatitis was studied by immunohistochemistry, ELISA and various other enzyme assays. The production of regenerating islet-derived 3β (REG3β) was determined by western blot and immunohistochemistry.


RESULTS
While cerulein treatment in non-diabetic mice resulted in acute pancreatitis followed by regeneration of the pancreas within 7 days, diabetes aggravated pancreatitis, inhibited the regeneration of the exocrine tissue and led to strong atrophy of the pancreas. The aggravation of pancreatitis by diabetes was characterised by decreased production of the anti-inflammatory protein REG3β, increased inflammation, augmented oedema formation and increased cell death during the acute phase of pancreatitis (p < 0.05). During the regenerative phase, diabetes augmented inflammation, increased cell death, reduced acinar cell expansion and increased the expansion of duct as well as interstitial cells, resulting in the formation of tubular complexes (p < 0.05). Administration of insulin reversed the observed phenotype in diabetic mice.


CONCLUSIONS
Diabetes aggravates acute pancreatitis and suppresses regeneration of the exocrine tissue. Thus, diabetes is not just a concomitant phenomenon of pancreatitis, but can have a fundamental influence on the progression of acute pancreatitis.
Institute for Experimental Surgery, University of Rostock, Schillingallee 69a, 18057 Rostock, Germany.
D
D
Zechner
M
M
Spitzner
A
A
Bobrowski
N
N
Knapp
A
A
Kuhla
B
B
Vollmar
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002108:Ceruletide / Q000009:adverse effects; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D010195:Pancreatitis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins / Q000032:analysis; D012038:Regeneration / Q000187:drug effects
D007004:Hypoglycemic Agents; D007328:Insulin; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C490253:Reg3b protein, mouse; D002108:Ceruletide