Acute pancreatitis involves the pancreas digesting itself resulting in severe abdominal pain, vomiting and systemic inflammation. Every year in the UK around 20,000 patients are diagnosed with the disease resulting in 1000 deaths. There is no immediate cure and treatment is restricted to intravenous fluid and nutritional support.
Dr Jason Bruce, from the Faculty of Life Sciences, who led the research, said “The major causes of pancreatitis include bile acid reflux from gall stones and excessive alcohol intake combined with a high fat diet. In fact, the incidence of acute pancreatitis significantly increases during the Christmas period when alcohol and fat consumption is at its highest amongst the general population. When alcohol and fat accumulate inside pancreatic acinar cells - the cells that secrete digestive enzymes into the gut - the resulting small molecules called metabolites deplete cellular energy levels and increase cellular calcium. This causes uncontrolled and catastrophic cell death and the cells burst, releasing their toxic enzymes which digest the pancreas and surrounding tissue.”
However, recent research from Dr Bruce’s laboratory published in the Journal of Biological Chemistry, shows that insulin, which is normally released from the beta cells of the pancreas, prevents these toxic effects of alcohol and fatty acid metabolites.
Dr Bruce and his team decided to look at insulin because it has been used successfully to treat obese pancreatitis patients by reducing fatty acids in the blood.
Diabetes makes pancreatitis worse and diabetics are at higher risk of developing pancreatitis and multiple organ failure. Moreover the incidence of pancreatitis is reduced in diabetics that receive insulin. Although tenuous, these studies suggested that insulin might have a protective role, however, it remained unclear how insulin was working. What makes the Manchester research unique is that it provides the first evidence that insulin directly protects the acinar cells, which is where the disease is initiated.
Acute pancreatitis is a sudden inflammation of the pancreas.
The pancreas is the large gland located in the upper part of the abdomen, behind the stomach. It produces digestive enzymes and hormones.
In pancreatitis, enzymes that normally are released into the digestive tract begin to damage the pancreas itself. The gland becomes swollen and inflamed. More enzymes are released into the surrounding tissues and bloodstream.
As a result, digestion slows down and becomes painful. Other body functions can be affected. The pancreas can become permanently damaged and scarred if attacks are severe, prolonged or frequent.
It is not known exactly why the enzymes start to damage the pancreas. But there are several known trigger of acute pancreatitis.
One of the most common causes of acute pancreatitis is gallstones. Gallstones that escape from the gallbladder can block the pancreatic duct. (The pancreatic duct delivers digestive enzymes from the pancreas to the small intestine.) When the pancreatic duct becomes blocked, enzymes can’t flow properly. They can back up into the pancreas. This causes the pancreas to become inflamed.
Dr Bruce explains: “Insulin works by restoring the energy levels of pancreatic acinar cells, which fuels the calcium pumps on the membrane of these cells. These calcium pumps help to restore cellular calcium and prevent the catastrophic cell death and autodigestion of the pancreas.”
He continues: “Although more research is needed to confirm that insulin works in animal models and human clinical trials, this study suggests that combined with tight control over blood glucose insulin may be an effective treatment for pancreatitis. Furthermore, if we can better understand how insulin works, then we might be able to design new and more effective drugs that might one day provide the first curative treatment for this disease”
Mild acute pancreatitis has a low mortality rate, but patients with severe acute pancreatitis are more likely to develop complications and have a much higher death rate. Although serum amylase and lipase levels remain the most widely used diagnostic assays for acute pancreatitis, other biomarkers and inflammatory mediators such as trypsinogens are being investigated for clinical use. Ranson’s criteria, the Imrie scoring system, the Acute Physiology and Chronic Health Evaluation (APACHE II) scale, and the Computed Tomography Severity Index are systems for classifying severity of this disease; the Atlanta classification is widely used to compare these systems and standardize clinical trials. New developments in imaging modalities such as endoscopic ultrasonography and magnetic resonance cholangiopancreatography increase the options available to physicians for determining the cause of pancreatitis and assessing for complications. Enteral nutrition is preferred to parental nutrition for improving patient outcomes. Clinical trials are ongoing to evaluate the role, selection, and timing of antibiotics in patients with infected necrosis.
Acute pancreatitis is a reversible inflammatory process of the pancreas. Although the disease process may be limited to pancreatic tissue, it also can involve peripancreatic tissues or more distant organ sites. Acute pancreatitis may occur as an isolated attack or may be recurrent. It has a variety of causes and can range in severity from mild to severe and life threatening. Some patients may require brief hospitalization, whereas others may be critically ill with multiple organ dysfunction requiring intensive care monitoring. Mild acute pancreatitis has a very low mortality rate (less than 1 percent), whereas the death rate for severe acute pancreatitis can be 10 to 30 percent depending on the presence of sterile versus infected necrosis.3 In the United States, up to 210,000 patients per year are admitted to a hospital for acute pancreatitis.
University of Manchester