**2. Biological mechanisms that underlie Insulin dependence**

Type 1 diabetes is a multifactorial autoimmune disease, which is characterized by T cell mediated damage to the insulin-secreting pancreatic β cells. The initial stages of the disease process feature insulitis, followed by the pancreatic islets' infiltration by mononuclear immune cells (including dendritic cells, macrophages, and T cells). This detrimental process leads to severe insulin depletion, and consequently

hyperglycaemia. Underlying this hyperglycemia are reasons like hepatic overproduction of glucose by glycogenolysis and gluconeogenesis accompanied by a decrease in the cellular uptake of circulating glucose. Insulin's absence, increases fat breakdown and the consequence of fatty acid oxidation is excessive production of ketones. These metabolic disturbances are serious enough to progressively cause central nervous system depression, coma, and death, if left untreated. Therefore, type 1 diabetes necessitates lifetime treatment with exogenous insulin as a survival-essential. Pancreatic β cell destruction rate shows inter-individual differences, yet, tends to be more aggressive in infants and young children [6]. Type 1 diabetes represents approximately 10% of all cases with diabetes. Its incidence is increasing worldwide at a rate of about 3% per year. The latest edition of the International Diabetes Federation (*IDF), Diabetes Atlas* shows that 1.1 million children and adolescents under the age of 20 live with type 1 diabetes [1]. Islet cells balance cellular glucose requirement with the glucose supply through blood, and this is illustrated in the following figure, **Figure 2** through insulin signaling pathway.

For individuals with type 1 diabetes or insulin-deficient forms of pancreatogenic (type 3c) diabetes, isolation of islets from a deceased donor pancreas with intrahepatic transplantation of allogeneic islets can result in amelioration of hypoglycemia, on-target glycemic control, improved quality of life, and insulin independence. Recent progress in techniques for islet isolation, islet culture, and peritransplant management of the islet transplant recipient has resulted in substantial improvements in metabolic and safety outcomes for patients. The metabolic benefits of islet transplantation are dependent on the count of islets transplanted that survive engraftment [7].
