Overview
Katie obtained her undergraduate degree in BSc Biomedical Sciences (Physiology) at Cardiff University. During her degree, she completed a Professional Training Year (PTY) placement within the Islet Biology Exeter (IBEx) team under supervision of Prof. Noel G. Morgan and Dr Mark Russell. Her PTY focused on using in vitro cell culture models to explore both the effect of anti-inflammatory cytokines on pancreatic β-cell viability and what signalling transduction mechanisms could be responsible.
Upon returning to Cardiff University, Katie completed her dissertation surrounding AMPA/KA receptor involvement in osteoarthritis using novel 3D in vitro models and in 2019, she graduated with a 1st Class BSc (Hons) degree.
Katie’s general interest is on how the pancreatic islet metabolically adapts or changes during type 1 and 2 diabetes progression.
Qualifications
- 2019: BSc (Hons) Biomedical Sciences (Physiology) with Professional Training Year (1st Class Honours)
Career
Katie’s previous experience included working within the IBEx team during her Professional Training Year (PTY) in the University of Exeter Medical School to investigate how some cytokines may promote cytoprotective effects within the pancreatic beta cell. Also, during her final year dissertation project at Cardiff University, Katie focused on how ionotropic receptor antagonism could modulate intracellular signalling pathways within a 3D, in vitro mechanical load model of osteoarthritis.
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Research
Research interests
Katie is interested in how the pancreatic alpha cell responds and may adapt to hypoglycaemia through changes to intrinsic alpha cell signaling pathways. This project is funded by Diabetes UK and supervised by Dr Craig Beall, Dr Kate Ellacott and Prof Noel G. Morgan.
Grants/Funding:
- Diabetes UK PhD Studentship 2019
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Publications
Journal articles
Cruz AM, Partridge KM, Malekizadeh Y, Vlachaki Walker JM, Weightman Potter PG, Pye KR, Shaw SJ, Ellacott KLJ, Beall C (2021). Brain Permeable AMP-Activated Protein Kinase Activator R481 Raises Glycaemia by Autonomic Nervous System Activation and Amplifies the Counterregulatory Response to Hypoglycaemia in Rats.
Frontiers in Endocrinology,
12Abstract:
Brain Permeable AMP-Activated Protein Kinase Activator R481 Raises Glycaemia by Autonomic Nervous System Activation and Amplifies the Counterregulatory Response to Hypoglycaemia in Rats
AimWe evaluated the efficacy of a novel brain permeable “metformin-like” AMP-activated protein kinase activator, R481, in regulating glucose homeostasis.Materials and MethodsWe used glucose sensing hypothalamic GT1-7 neuronal cells and pancreatic αTC1.9 α-cells to examine the effect of R481 on AMPK pathway activation and cellular metabolism. Glucose tolerance tests and hyperinsulinemic-euglycemic and hypoglycemic clamps were used in Sprague-Dawley rats to assess insulin sensitivity and hypoglycemia counterregulation, respectively.ResultsIn vitro, we demonstrate that R481 increased AMPK phosphorylation in GT1-7 and αTC1.9 cells. In Sprague-Dawley rats, R481 increased peak glucose levels during a glucose tolerance test, without altering insulin levels or glucose clearance. The effect of R481 to raise peak glucose levels was attenuated by allosteric brain permeable AMPK inhibitor SBI-0206965. This effect was also completely abolished by blockade of the autonomic nervous system using hexamethonium. During hypoglycemic clamp studies, R481 treated animals had a significantly lower glucose infusion rate compared to vehicle treated controls. Peak plasma glucagon levels were significantly higher in R481 treated rats with no change to plasma adrenaline levels. In vitro, R481 did not alter glucagon release from αTC1.9 cells, but increased glycolysis. Non brain permeable AMPK activator R419 enhanced AMPK activity in vitro in neuronal cells but did not alter glucose excursion in vivo.ConclusionsThese data demonstrate that peripheral administration of the brain permeable “metformin-like” AMPK activator R481 increases blood glucose by activation of the autonomic nervous system and amplifies the glucagon response to hypoglycemia in rats. Taken together, our data suggest that R481 amplifies the counterregulatory response to hypoglycemia by a central rather than a direct effect on the pancreatic α-cell. These data provide proof-of-concept that central AMPK could be a target for future drug development for prevention of hypoglycemia in diabetes.
Abstract.
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