Abstract
ATP-sensitive potassium (KATP) channels, composed of the SUR1 and Kir6.2 subunits encoded by the ABCC8 and KCNJ11 genes, are critical regulators of membrane excitability and insulin secretion in pancreatic β-cells. Gain-of-function (GOF) mutations in these genes cause neonatal diabetes mellitus through impaired insulin secretion and persistent hyperglycemia, whereas loss-of-function (LOF) mutations lead to congenital hyperinsulinism (CHI) with hypoglycemia due to β-cell hyperexcitability. I have addressed a paradoxical form of maturity-onset diabetes of the young (MODY) arising from KATP mutations, in which patients transition from CHI to glucose intolerance later in life. My experiments indicate that many KATP mutations associated with later onset diabetes (MODY) are LOF, thereby significantly expanding the cohort of patients affected by this form of MODY.
Committee Chair
Colin Nichols
Committee Members
Fumihiko Urano, Jonathan Silva
Degree
Master of Science (MS)
Author's Department
Biomedical Engineering
Document Type
Thesis
Date of Award
Winter 12-17-2025
Language
English (en)
Recommended Citation
Zhang, Hao, "Functional Characterization of ABCC8 Mutations Potentially Linked to the Transition from Hyperinsulinemic Hypoglycemia to Diabetes" (2025). McKelvey School of Engineering Theses & Dissertations. 1306.
https://openscholarship.wustl.edu/eng_etds/1306