The Protective Effects of Sprotone during Acute Pancreatitis.

Abstract

Acute pancreatitis is an inflammatory disease characterised by pancreatic autodigestion and in severe cases is frequently accompanied by sepsis. Pancreatitis and diabetes share a bidirectional relationship. Endogenous insulin has been found to have direct protective effects in Caerulein and (POA)/ethanol-induced pancreatitis in Ins2Akita diabetic mice and PACIRKO mice, where pancreatitis was worse. The molecular mechanism was identified to be the Akt-mediated phosphorylation of PFKFB2, upregulating glycolysis. Although insulin infusion seems like a therapeutic solution, safety concerns remain, especially in severe AP patients. Therefore Sprotone, a sprouted multi-grain composition with both anti-diabetic and insulin-mimetic properties was investigated for its putative protective effects. Ethanol extracts of Sprotone were found to be protective in cellular models of AP and activated the same cellular mechanism as insulin. Sprotone administration also markedly reduced the caerulein induced AP in C57BL/6 mice. Hence, we aimed to identify the active ingredients of Sprotone, a comparison was made with the unsprouted form, which failed to attenuate the POA-induced cytotoxic calcium overload suggesting that sprouting may be responsible for the protective effects of Sprotone. LC MS analysis revealed that eighty-nine compounds were significantly increased in Sprotone which also included amino acids, like Phenylalanine–Threonine, Proline–Alanine–Arginine etc. Hence, we further wanted to see if amino acids would also exert similar protective effects, amino acids exhibited protective effects in cellular models of AP and activated the PI3K/Akt as the major downstream signalling pathway, but the AAs induced PFKFB2 phosphorylation was less distinct, so the presence of amino acids in Sprotone could at least be in part responsible for the insulin-mimetic action. Further we investigated if Sprotone had any protective effects on caerulein induced AP in diabetic Ins2Akita. Sprotone administration markedly reduced the plasma amylase and reduced the pancreatic wet dry ratio, though in histological assessment, Sprotone did not cause a significant reduction. Further since there is a link between severity of pancreatitis and impaired gut function and Sprotone is rich in fibre, we investigated if Sprotone had protective effects on the impaired gut function. Sprotone administration did not necessarily have an impact, suggesting that the protective effects of Sprotone observed are primarily attributed to the insulin-mimetic properties.

Date of Award	26 Jun 2025
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Jason Bruce (Main Supervisor), Jo Pennock (Co Supervisor) & Ian Roberts (Co Supervisor)