The Reg Gene and Islet Cell Repair and Renewal in Type 1 Diabetes
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The characteristic inability to maintain glucose homeostasis in diabetes mellitus reflects an absolute or partial insulin deficiency. This lack of insulin is due to an overall reduction in the mass of properly functioning β-cells. Such a reduction occurs as a result of a combination of an increased rate of cell destruction and a decreased rate of cell repair and renewal. Whilst considerable attention has been focussed on the elucidation of factors resulting in β-cell loss, much less information is available regarding possible common genetic control mechanisms implicating alterations in islet cell repair and/or adaptive β-cell regeneration as causative factors in diabetes. The difficulties in performing studies of β-cell repair and renewal in diabetes in man are obvious. Thus, it has been earlier investigations performed in models of diabetes which have provided some insight into the defence and repair/regeneration mechanisms activated in the islet cells following injury and onset of disease(11). The hypothesis that pancreatic β-cells possess defence mechanisms against cell injury gained support from observations that islets are able to survive and even recover functional activity after exposure to cytotoxic attack or disturbed metabolism (21,17). However, the magnitude and subsequent effectiveness of the islet cell defence and repair mechanisms is dependent upon the nature and extent of the cytotoxic insult (5). Thus, exposure of rodent islets to alkylating agents (6), IL-1β(8) or heat shock (25) induces a sustained but reversible inhibition of β-cell function. On the other hand, treatment of mouse islets with streptozotocin (SZ) impairs mitochondrial gene expression leading to a persistent decrease in glucose stimulated insulin secretion (20).
KeywordsIslet Cell Pancreatic Islet Glucose Stimulate Insulin Secretion Nonobese Diabetic Mouse Heat Shock Protein HSP70
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