Pancreas biology, pathology, and tissue engineering

Abstract

Diabetes is a chronic condition that is increasing at an alarming rate. In 1985, there were approximately 30 million people with diabetes worldwide. Today the International Diabetes Federation estimates that more than 230 million people around the world have diabetes and this total is expected to rise to 350 million by 2025. Not only is diabetes expensive to treat but also the complications of the condition account for 5-10% of total healthcare spending globally. The complications are numerous and devastating, causing blindness, cardiovascular disease, limb amputations, kidney failure, and many more. Until the discovery of insulin in 1921 by Dr. Frederick Grant Banting, Charles Best, James Bertram Collip, and Dr. James Macleod, diabetes was a death sentence. Although the discovery of insulin lead to people surviving where previously they would have died, it was certainly not a cure. It was only after many years of treatment that it became evident that while people could be kept alive on insulin, it was difficult if not impossible to achieve the tight glucose control required to avoid the risk of complications. There are two main types of diabetes, Type 1 and Type 2. Type 1 diabetes Mellitus is generally associated with a sudden onset of symptoms and is characterized by the cellular-mediated autoimmune destruction of the insulin containing -cells within the pancreatic islets of Langerhans and commonly develops during childhood (The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, 2003; Atkinson and McClaren, 1994). Type 1 diabetes (T1D) develops when the body is unable to maintain circulating glucose concentrations within the normal physiological range due to a reduction or complete absence of circulating insulin. A person with T1D will suffer acute symptoms including weight loss, extreme thirst, increased urination, and if left untreated, will result in coma and death. The only current treatment for T1D is daily administration of insulin either via injection or subcutaneous insulin infusion (pump therapy). Treatment of diabetes with insulin carries an associated risk of hypoglycaemia. People who experience this sudden drop in blood glucose may find it not only causes physical symptoms but also the very fear of it occurring may impact negatively on their lives and their diabetes control. Type 2 diabetes (T2D) is often, mistakenly, considered to be a milder form of diabetes as it does not present with the same acute symptoms. Rather than an absolute deficiency of insulin, there may be high circulating levels of insulin but cellular insensitivity combined with signaling defects prevent the cells from taking up glucose. Despite the less obvious onset, poor glycemic control in T2D has exactly the same consequences in terms of complications as Type 1. Often because the onset usually occurs later in life and presents with symptoms such as fatigue, thirst, or recurrent infections, it may go undiagnosed for a many years. People with T2D may be diagnosed due to the complications they present with rather than an initial diagnosis of diabetes. There are many therapies available for the treatment of T2D but compliance is poor and these, like insulin, are also not a cure. Although the discovery of insulin and improved drug therapies have saved many lives, there is currently no cure for diabetes. The ultimate goal of diabetes research is to address the loss of -cells in an enduring and physiologically accurate way so that a cure can be affected and complications prevented. Tissue engineering offers the potential to do this. In order to understand what is required of an "engineered tissue", it is first important to have a good working knowledge of what is required from such a tissue. The following sections will describe the pancreas biology and pathology before addressing the strategies for tissue engineering. © Springer Science+Business Media, LLC 2009.