Justin J. Crowder

Real-time in vivo analysis of murine β cells reveals autophagic flux defects before onset of autoimmune diabetes

Olha Melnyk, Charanya Muralidharan, Bryce E. Duffett, Alissa N. Muncy et autres

Autophagy, a vital catabolic process, plays a crucial role in maintaining pancreatic β cell function and is disrupted in established type 1 diabetes. However, it is unclear when and how this critical cell process becomes defective during type 1 diabetes pathogenesis. To …

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Ubiquitin-conjugating enzyme membrane anchor Cue1 confers resistance to hygromycin B in Saccharomyces cerevisiae

James A. Avaala, Melissa Palackel, Ian M Tesch, Joseph Gumina et autres

deletion, consistent with a shared role for Cue1 and Ubc7 in ER and INM protein quality control.

Dysfunctional β-cell autophagy induces β-cell stress and enhances islet immunogenicity

Matthew C. Austin, Charanya Muralidharan, Saptarshi Roy, Justin J. Crowder et autres

Background Type 1 Diabetes (T1D) is caused by a combination of genetic and environmental factors that trigger autoimmune-mediated destruction of pancreatic β-cells. Defects in β-cell stress response pathways such as autophagy may play an important role in activating and/or exacerbating the immune …

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Real Time In vivo Analysis of Pancreatic Beta-cell Autophagic Flux Reveals Impairment Before Onset of Autoimmune Diabetes

Olha Melnyk, Charanya Muralidharan, Bryce E. Duffett, Alissa N. Novak et autres

Abstract The catabolic pathway of autophagy is critical for pancreatic beta-cell function and is defective in established type 1 diabetes (T1D). However, it is unclear when and how this critical cell process becomes defective during diabetes pathogenesis. To study the nature of …

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1443-P: Real-Time In Vivo Analysis of Beta-Cell Autophagy in Autoimmune Diabetes

OLHA MELNYK, Charanya Muralidharan, Michelle M. Martinez Irizarry, Justin J. Crowder et autres

Type 1 Diabetes (T1D) is an autoimmune disease caused by a combination of genetic and environmental factors. The onset of disease is associated with autoimmune attack against pancreatic beta-cells leading to a reduction of their number. While a role for the beta-cell …

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15-OR: Mitochondrial NRF2 in ß-cell Oxidative Stress Response

ALISSA NOVAK, Justin J. Crowder, MICHELLE MARASCO, Amelia K. Linnemann

β-cells are highly metabolic and vulnerable to a variety of exogenous stressors, including excess glucose and proinflammatory cytokines. Many of these stressors elicit the accumulation of reactive oxygen species (ROS) , which can cause oxidative damage and lead to cell death. To …

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Stabilization protects islet integrity during respirometry in the Oroboros Oxygraph-2K analyzer

Justin J. Crowder, Ziqian Zeng, Alissa N. Novak, Nathan J. Alves et autres

Metabolic dysfunction of β-cells has been implicated as a contributor to diabetes pathogenesis, and efforts are ongoing to optimize analytical techniques that evaluate islet metabolism. High-resolution respirometry offers sensitive measurements of the respiratory effects of metabolic substrates and customizable manipulation of electron …

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1237-P: Generation of Targeted Nanoparticles for ß-Cell-Selective Delivery of Antioxidant Drugs

ALISSA NOVAK, Tanmaye Nallan Chakravarthula, Justin J. Crowder, Nathan J. Alves et autres

β-cells are highly metabolic and vulnerable to a variety of exogenous stressors, many of which elicit the generation of reactive oxygen species (ROS). Endogenous adaptive responses can restore homeostasis after excessive ROS elevation. If the endogenous adaptive response fails, ROS accumulation can …

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1239-P: Evidence of Altered Alpha- and Beta-Cell Lysosomes prior to Onset of Type 1 Diabetes

Charanya Muralidharan, Justin J. Crowder, Amelia K. Linnemann

Autophagic degradation is a dynamic recycling process that contributes to cellular homeostasis and mitigation of cellular stress. While there are multiple forms of -phagic degradation processes, a common endpoint is the final degradation step in the lumen of the acidic lysosomes. Post-mitotic …

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Pancreatic beta cell autophagy is impaired in type 1 diabetes

Charanya Muralidharan, Abass M. Conteh, Michelle R. Marasco, Justin J. Crowder et autres

AIMS/HYPOTHESIS: Pancreatic beta cells are subjected to exogenous damaging factors such as proinflammatory cytokines or excess glucose that can cause accumulation of damage-inducing reactive oxygen species during the pathogenesis of diabetes. We and others have shown that beta cell autophagy can reduce …

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GYS1 or PPP1R3C deficiency rescues murine adult polyglucosan body disease

Erin E. Chown, Peixiang Wang, Xiaochu Zhao, Justin J. Crowder et autres

OBJECTIVE: Adult polyglucosan body disease (APBD) is an adult-onset neurological variant of glycogen storage disease type IV. APBD is caused by recessive mutations in the glycogen branching enzyme gene, and the consequent accumulation of poorly branched glycogen aggregates called polyglucosan bodies in …

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Pancreatic Beta Cell Autophagy is Impaired in Type 1 Diabetes

Charanya Muralidharan, Abass M. Conteh, Michelle R. Marasco, Justin J. Crowder et autres

Abstract Aims/hypothesis Pancreatic beta cells are highly metabolic secretory cells that are subjected to exogenous damaging factors such as proinflammatory cytokines or excess glucose that can cause accumulation of damage-inducing reactive oxygen species (ROS) during the pathogenesis of diabetes. We and others …

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