# Dynamin function in beta cell autophagy

> **NIH NIH R56** · MEDICAL COLLEGE OF WISCONSIN · 2021 · $195,000

## Abstract

PROJECT SUMMARY
Diabetes affects over 30 million Americans, yet its epidemic is still rising at an alarming rate. The
progressive decline of pancreatic β cell function and mass is a hallmark of the disease, but no
medications prevent this decline. Interestingly, a fasting-mimicking diet known to activate autophagy
stops this decline, and it also reverses diabetes in mice. Recent progress has increasingly recognized
autophagy as a potential therapeutic target to treat diabetes because autophagy has a role in protecting
β cells against pathogens and diabetic stress. However, the fundamental nature of β cell autophagy
remains poorly understood, particularly in the molecular process governing autophagic membrane
fission. Our recent data reveal that dynamin, a family of large GTPase proteins known to regulate
endocytosis and insulin secretion, directly alters β cell autophagy. Live-cell imaging reveals that
dynamin molecules translocate to autolysosomes and drive autolysosome fission. Conditional dynamin
deletion causes striking autophagy defects in β cells. These new findings fuel tremendous interest in
understanding the molecule mechanisms at play throughout the β cell autophagy cycle. We
hypothesize that dynamin plays a direct and crucial role in β cell autophagy that has not been
characterized. Mechanistically, we suspect that dynamin regulates β cell autophagy through regulating
autolysosome fission and autophagic transport. These processes may be essential to protect β cells
against chronic metabolic stress. We have assembled a team with substantial expertise in β cell biology,
super-resolution imaging, biochemical signaling, mouse genetic models, and diabetes to test this
hypothesis. We propose three specific aims. First, we will define the role of dynamin in β cell
autolysosome fission. This fission step is necessary for autolysosome-to-lysosome transformation in
each autophagic cycle, but its mechanism remains poorly understood. We expect that β cells use
dynamin to resolve their autolysosomes into lysosomes in autophagy. Second, we will investigate how
dynamin regulates β cell microtubules to alter autophagic transport. These studies may uncover a
previously unappreciated pathway for dynamin to regulate autophagy. Third, we will examine dynamin-
regulated β cell autophagy in vivo. We have generated dynamin isoform-specific mouse models. These
unique models make it possible to evaluate dynamin-regulated β cell autophagy in vivo and its
protection against the metabolic stress of diabetes. Together, these studies will provide new insight into
the molecular regulation of β cell autophagy mediated by different dynamin isoforms. Their outcomes
will advance the fundamental understanding of β cell autophagy that profoundly impacts islet function
and diabetes pathogenesis.

## Key facts

- **NIH application ID:** 10473913
- **Project number:** 1R56DK128091-01A1
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** XUELIN LOU
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $195,000
- **Award type:** 1
- **Project period:** 2021-09-22 → 2023-03-21

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10473913

## Citation

> US National Institutes of Health, RePORTER application 10473913, Dynamin function in beta cell autophagy (1R56DK128091-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10473913. Licensed CC0.

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