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Human Mutations In VPS41 And Their Effects On Insulin Secretion

Insulin is released through regulated secretion, meaning it is released in response to an extracellular signal. The initial step of this secretion is the formation of insulin secretory granules (ISGs), which contain the insulin to be released. The mechanism by which ISGs form is not entirely known, but our lab has previously shown that cells without the protein VPS41 have fewer ISGs and decreased insulin secretion. In this study, we reproduced six mutations in VPS41 that are associated with type 2 diabetes in humans and introduced them in INS-1 beta cells. Secretion assays will be conducted to determine rates of insulin secretion. This will indicate which mutations, if any, have an effect on insulin secretion and ISGs formation. This insight will show which parts of VPS41 could have a role in ISGs formation, which in turn, could shed light on the mechanism of ISGs formation.

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