# The Role of Microtubule Sliding in Regulation of Insulin Secretion

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2020 · $30,220

## Abstract

Abstract
Diabetes mellitus is a major metabolic disorder currently affecting 5–10% of the population in the western
societies. In type-2 diabetes, which accounts for 90% of all diabetes, insulin is not released into the
bloodstream in sufficient amounts. Insulin secretion is a function of pancreatic beta cells. Beta cells have to
secrete restricted doses of insulin, in order to reduce blood sugar to normal levels but do not completely
deplete it; this requires tight coordination between intracellular insulin storage and secretion. Our data indicate
that this coordination is regulated by cytoskeletal polymers microtubules (MTs), which are known to serve as
intracellular highways; molecular motors such as kinesin-1, move along MTs to transport and park membrane
organelles and insulin granules at specific cellular locations. Our lab has shown that the dense MTs in
pancreatic beta cells restrain insulin granules in “cages”, restricting insulin granule availability for glucose-
stimulated insulin secretion. Previous studies have shown that targeted inactivation of kinesin-1 leads to
hyperglycemia and the authors concluded that this is due to loss of trafficking of insulin by kinesin-1. Whether
the MT network is remodeled and configured by this kinesin as well is not known and therefore may be part of
the underlying hyperglycemic phenotype observed in the targeted inactivation of conventional kinesin in the
pancreas. One possibility for resolution of these cages is through the active transport of MTs by a kinesin
motor. Interestingly, I have found that glucose stimulation promotes the novel MT sliding process in beta cells. I
hypothesize that MT sliding resolves “caged” insulin granules and/or impacts MT network configuration in
pancreatic beta cells for their proper function. My specific aims are (1) to determine glucose-dependent
pathways and mechanisms that facilitate MT sliding and (2) to elucidate the role of MT sliding in MT-
dependent regulation of insulin release. I proposed to utilize high-end approaches for high- and super-
resolution biological imaging, computational modeling, and various glucose secretion assays to achieve these
aims. The discovery of MTs serving as regulatory components in beta cells is a new and exciting topic in the
field.

## Key facts

- **NIH application ID:** 10001328
- **Project number:** 5F31DK122650-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Kai M. Bracey
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $30,220
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001328

## Citation

> US National Institutes of Health, RePORTER application 10001328, The Role of Microtubule Sliding in Regulation of Insulin Secretion (5F31DK122650-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10001328. Licensed CC0.

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