Diabetes aggravates acute pancreatitis and inhibits pancreas regeneration in mice

Abstract

Aims/hypothesis 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 isletderived 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/interpretation 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.

Serotonin regulates amylase secretion and acinar cell damage during murine pancreatitis

“…Currently, we do not have evidence for a role of diabetes in the development of pancreatitis observed in TPH1 −/− mice. Indeed, while diabetes has been shown to aggravate cerulein-induced pancreatitis by increasing inflammation during the acute phase and promoting metaplasia,49 these events were not observed in our experimental model.…”

Insulin Protects Pancreatic Acinar Cells from Palmitoleic Acid-induced Cellular Injury

“…The latter has major pathophysiological implications because pancreatic necrosis leads to a spiral of self-perpetuating tissue injury and systemic inflammation culminating in multiple organ failure (1–5). Although these findings are novel, several lines of evidence from animal studies and human clinical studies suggest that insulin might have a protective role during pancreatitis (9, 12, 13, 16, 18–21, 36–43). …”

“…In streptozotocin (STZ)-induced diabetic mice, in which insulin secretion is impaired, caerulein-induced acute pancreatitis is much worse than in control mice (16). However, this was prevented by exogenously applied insulin (16).…”

“…However, this was prevented by exogenously applied insulin (16). In l -arginine-induced pancreatitis, acinar cells surrounding the islets of Langerhans remain relatively intact compared with distal injured acinar cells suggesting a paracrine protective role for insulin (12, 13).…”

“…Evidence suggests that insulin may ameliorate the course of clinical acute pancreatitis (9–11) and protect against experimentally induced pancreatitis (12–16). In addition, ∼50% of diabetic patients exhibit pancreatic exocrine lesions characteristic of chronic pancreatitis (17), and type 2 diabetics have an ∼3-fold increased risk of developing acute pancreatitis (18).…”