Investigation of the genetic basis of insulin hypersecretion in a mouse model of pancreatic islet failure

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Type 2 diabetes is a chronic disease that is associated with blindness, kidney failure, heart attacks and stroke and these are secondary to high blood sugar levels. Thus, determining the cause of high blood sugar levels in type 2 diabetes will lead to better management of the disease and ease the financial burden on the public health system. High blood sugar in type 2 diabetes results from the inability of the body to secrete enough insulin. Insulin is the main hormone that lowers blood sugar levels and is produced by the pancreas. The reason for reduced insulin secretion in type 2 diabetes is not known. Paradoxically, it has been shown that some people who are at an increased risk of developing diabetes (eg people with obesity or a family history of diabetes) secrete more insulin than normal. It is not clear why this is, but a few studies have suggested that reducing insulin secretion in these circumstances can protect the pancreas and preserve its ability to secrete the appropriate amount of insulin. The DBA-2 is a mouse strain that like humans with type 2 diabetes, its pancreas can also fail to secrete the appropriate amount of insulin and under these circumstances becomes diabetic. Furthermore our laboratory has generated evidence that shows that like people who are at risk of diabetes, DBA-2 mice in fact secrete more insulin prior to becoming diabetic. Whether the cause of this increased insulin secretion is linked to the eventual reduction of secretion is not known. The aim of this study is to identify the gene that causes increased insulin secretion in the DBA-2 mouse. Furthermore, genetically manipulated animals will be produced that contain only this gene to determine its effect on insulin secretion. Should the identification of this gene be related to the eventual failure of the pancreas to secrete enough insulin, then it would provide a target for drug therapy to correct insulin levels and therefore reduce blood sugar levels.