Date Approved

2012

Degree Type

Open Access Thesis

Degree Name

Master of Science (MS)

Department or School

Chemistry

Committee Member

Deborah Heyl-Clegg

Committee Member

Maria Milletti

Committee Member

Timothy Brewer

Committee Member

Ross Nord

Committee Member

Deborah de Laski-Smith

Abstract

Pancreatic beta cells secrete insulin, an endocrine hormone that regulates blood glucose levels and maintains normal physiological activity in humans and animals. Diabetes mellitus type II is a consequence of the gradual destruction of these important cells, likely by human islet amyloid polypeptide (hIAPP) that is co-secreted with insulin. Increasing health care costs, coupled with the World Health Organization’s prediction of a worldwide diabetic epidemic by year 2030, make experimental diabetes research a crucial prologue to future clinical trials in prevention, diagnosis, and treatment of Diabetes mellitus type II. Our experimental set-up simulates hIAPP peptide fragment and pancreatic beta cell membrane interactions, and it uses density functional methods and circular dichroism spectroscopic analysis of the hIAPP molecule to uncover factors that initiate and promote progression of beta cell death. Results from our study establish the potential role of hIAPP and a two-step molecular mechanism of pancreatic beta cell damage in diabetes mellitus type II.

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