Regulation of Inositol 1,3,4-Triphosphate 5/6-Kinase in Pancreatic Beta Cells: Implications for Glucose-Stimulated Insulin Secretion

Author

• Preston Reed, University of South AlabamaFollow

Date of Award

5-2026

Document Type

Undergraduate Thesis

Degree Name

BS

Department

Biology

Faculty Mentor

Lucia Plant, Ph.D.

Advisor(s)

Jason Strickland, Ph.D., Jonathan Perez, Ph.D.

Abstract

Dysregulation of insulin secretion is fundamental to the pathogenesis of diabetes, a growing global health concern. Prolonged exposure to elevated glucose levels contributes to pancreatic β-cell dysfunction and progression of type 2 diabetes. While the core mechanisms of glucose-stimulated insulin secretion (GSIS) are well established, less is known about how β-cell glucose responsiveness is modulated under chronic hyperglycemic conditions. Emerging evidence suggests that nutrient-sensing pathways and intracellular signaling networks play key roles in β-cell adaptation to metabolic stress. Inositol phosphate signaling regulates cellular metabolism, calcium dynamics, and mTORC1 activity, processes central to insulin secretion. Inositol 1,3,4-trisphosphate 5/6-kinase (ITPK1) is a key enzyme in this pathway that generates higher-order inositol phosphates, but its role in pancreatic β-cell glucose sensing remains largely unexplored. This study aimed to determine how glucose exposure regulates ITPK1 expression and how ITPK1 influences insulin secretion. We examined acute versus prolonged glucose exposure and evaluated the effects of ITPK1 knockdown on GSIS. We hypothesized that chronic glucose exposure increases ITPK1 expression and enhances β-cell glucose sensitivity. To test this, we quantified ITPK1 protein and mRNA expression and performed functional GSIS assays following ITPK1 knockdown. Our findings show that ITPK1 expression is upregulated under chronic high glucose conditions and that ITPK1 knockdown alters insulin secretion in a manner consistent with reduced β-cell glucose sensitivity. These results identify ITPK1 as a previously underexplored regulator of β-cell function and suggest that inositol phosphate signaling contributes to the modulation of insulin secretion under hyperglycemic conditions, providing insight into β-cell dysfunction and potential therapeutic targets.

Recommended Citation

Reed, Preston, "Regulation of Inositol 1,3,4-Triphosphate 5/6-Kinase in Pancreatic Beta Cells: Implications for Glucose-Stimulated Insulin Secretion" (2026). Honors Theses. 143.
https://jagworks.southalabama.edu/honors_college_theses/143