# Cytoskeleton-mediated regulation of insulin secretion hot spots in pancreatic beta cells

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2024 · $34,250

## Abstract

Project Summary
Insulin secretion from pancreatic β cells is crucial to maintaining blood glucose homeostasis, allowing cells
throughout the body to take up glucose from the blood and obtain nutrients for normal cellular processes. In
type 2 diabetes, however, peripheral tissues become insulin resistant, β cells over-secrete insulin to
compensate, and eventually β cells become dysfunctional. It is therefore necessary to thoroughly understand
the mechanisms of insulin secretion in order to identify potential therapeutic targets for type 2 diabetes
treatment. Insulin secretion is known to predominantly occur at the vascular face of the β cell, at regions
termed “hot spots.” Hot spots are characterized by proteins common to the active zone of neurons as well as
proteins of cortical microtubule-stabilizing complexes and focal adhesions. Our laboratory has also found that
microtubule destabilization promotes insulin secretion specifically at hot spots. Others have shown that the
actin cytoskeleton also plays a critical regulatory role in insulin secretion. Given the known connections of
microtubules, focal adhesions, and actin with known hot spot proteins, it is likely that the interplay of these
cytoskeletal elements is essential for the hot spot organization and function. I therefore hypothesize that insulin
secretion hot spots are “secreting adhesions”: mechanosensitive subcellular domains which use cytoskeletal
regulation to accomplish directed and clustered secretion. My specific aims are to 1) characterize the
cytoskeleton networks, their interplay, and other hot spot components in β cells; and to 2) test if MT-
regulated RhoA-dependent contractility promotes clustered secretion via secreting adhesion
assembly. To address these aims, I will use high- and super-resolution fixed and live-cell imaging techniques
combined with computational analyses. Improving the understanding of hot spot identity and establishment via
the cytoskeleton will contribute to overall knowledge of insulin secretion, and potentially uncover novel targets
for diabetes therapeutics.

## Key facts

- **NIH application ID:** 10867300
- **Project number:** 5F31DK136344-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Margret A Fye
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $34,250
- **Award type:** 5
- **Project period:** 2023-06-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10867300

## Citation

> US National Institutes of Health, RePORTER application 10867300, Cytoskeleton-mediated regulation of insulin secretion hot spots in pancreatic beta cells (5F31DK136344-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10867300. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*