Beta Cell Replacement Therapy

Abstract

Type 1 Diabetes mellitus (T1D) is an autoimmune disorder caused by destruction of pancreatic beta cells which produce insulin. Current estimates have shown that T1D affects about 0.4 to 0.8% of the population worldwide accounting for 5-10% of all diabetes cases (Stock and Bluestone, 2004). It is seen as an increasing health hazard. For T1D, exogenous insulin administration is the most widely used treatment. However, this treatment has several limitations including development of secondary health complications over time. There are several approaches already in practice to replace the damaged beta cells in T1D. They include whole organ pancreas or isolated islet cell transplantation. Several novel approaches are currently in development such as expansion of adult beta cells and stem/progenitor cells which can be transformed into beta cells. This review summarizes recent progress made in beta cell replacement therapy for T1D. Diabetes mellitus has been known for thousands of years. Diabetes comes from an ancient Greek word coined by Arataeus of Cappadocia, and mellitus from the Latin word honey associated with sweet urine. (Medvei, 1993). The pathogenesis of T1D has been attributed to an autoimmune response. Currently the mechanism that triggers this disease is still unknown, but it seems to be a combination of environmental and genetic factors. T-cells in the host’s body become sensitized to protein that naturally occurs in the beta cells of the pancreas and the immune system begins to mount a specific attack leading to destruction of the islets of Langerhans. Several candidate proteins have been identified including GAD65, insulin, and ZnT8 (Harlan et al., 2009, Shapiro et al., 2003). Reducing the autoimmune effect in beta cell replacement is very important, but before moving onto the strategies for beta cell replacement therapy it is important to describe the standard therapy for T1D and how it falls short of providing for all the needs of diabetic patients. Exogenous insulin therapy continues to be the leading therapy for T1D today, but there are several complications associated with it. However, even intensive monitoring of blood glucose and injection of insulin is not enough to halt the secondary complications of diabetes (Harlan et al., 2009). Diabetes mellitus can decrease patients’ lifespan, especially in severe cases. Lowered blood sugar levels, which can result if too much insulin is administered, can also lead to a hypoglycemic episode (Cooke and Plotnick, 2008). These episodes are typified by ketoacidosis, where in an effort to find energy, the body burns fatty acids leading to the production of acidic ketones that can be detected by an alcoholic smell on the breath. Hypoglycemic episodes can lead to coma and even death, and is considered