**2. Molecular mechanism of beta cell dysfunction**

#### **2.1. Early events after islet transplantation**

The liver is the most commonly used site for transplantation of islets. Data supporting the use of this transplant site came from autologous islet transplants in patients with chronic pancreatitis, which showed that islets can function inside the liver for several years. There are several drawbacks associated with the liver as a host site for islets. Major factors affect‐ ing islet function include hypoxia, drug toxicity and instant blood-mediated inflammatory reaction (IBMIR). Together, these events may lead to loss of up to 75% of islet transplant mass. IBMIR is primarily a response of innate immune system to isolated islets. Major char‐ acteristics of IBMIR include activation of coagulation and complement cascades and infiltra‐ tion of inflammatory cells. Several approaches are adopted to minimize the deleterious effects of IBMIR which include infusion of low molecular weight dextran sulfate and also inclusion of anti-inflammatory molecules during the infusion of islets. Besides the innate im‐ mune response, islets transplanted into liver may experience low oxygen tension. Activation of resident Kupffer cells may pose additional risk to islet survival. In addition, high concen‐ trations of immunosuppressive drugs in the portal vein are likely to exert toxic effect on the transplanted islet mass [6].
