Grant: Doctoral: Vanier Canada Graduate Scholarships

Supervisor: Dr. C. Bruce Verchere, University of British Columbia Diabetes affects over 537 million people worldwide, including 5.7 million Canadians. There are two major types of diabetes: type 1 diabetes (T1D) and type 2 diabetes (T2D). In both cases, diabetes occurs because cells in the pancreas that produce insulin are either destroyed (T1D) or defective (T2D). Insulin is the main hormone that controls blood sugar levels. High blood sugar levels occur because not enough insulin is made (T1D) or insulin is not used properly (T2D). Cells in the pancreas make insulin and also another hormone called islet amyloid polypeptide (IAPP), which work together to control blood sugar levels. Both insulin and IAPP are first made as the immature forms, proinsulin and proIAPP. Individuals with diabetes have higher levels of the immature forms, proinsulin and proIAPP, in their blood compared to the mature forms, insulin and IAPP. These immature forms do not function properly compared to the mature forms. It is still not understood why people with diabetes have higher levels of proinsulin and proIAPP. I aim to address this by precisely understanding why proinsulin and proIAPP are not cut properly to form insulin and IAPP in diabetes. To achieve this, I will 1) use cells from human pancreas organ donors and gene editing technology to understand what the normal process of cutting proinsulin to insulin, and proIAPP to IAPP is in humans, and 2) I will use blood samples from people with diabetes to measure the amounts and types of proinsulin and proIAPP in each donor. The goal is to gain a better understanding of how proinsulin and proIAPP are normally cut in non-diabetic individuals, and how this process changes in people with diabetes. Aim 1 will allow us to potentially find new targets for medication for diabetes, and Aim 2 will allow us to determine whether measuring proinsulin and proIAPP in the blood will help us to predict the likelihood of developing T1D and T2D.