Staff Profile

Background

I obtained a BSc in biomedical science from the University of Hull in 2001 and a PhD from Newcastle University in 2004. My interest in diabetes research continued during post-doc positions in the Diabetes Research Group at Newcastle University and during a travel fellowship at the University of Michigan, USA in 2007 (funded by EMBO/EFSD). In 2008 I was awarded the RD Lawrence Fellowship from Diabetes UK followed by the Newcastle University Research Fellowship in 2014. I was awarded a lectureship in 2020.

Qualifications

PhD - Newcastle University, UK
BSc(hons) - Hull University, UK

Previous Positions

2020-Present: Lecturer

2014-2020: Newcastle University Research Fellow

2008-2013: RD Lawrence Research Fellow, University of Newcastle

2007: EMBO/EFSD Travel Fellow, University of Michigan, USA

2004-2007: Research Associate, University of Newcastle

Memberships

Diabetes UK
Biochemical Society
European Association for the Study of Diabetes

I am a member of the Biosciences Institute and my work contributes to the Regenerative Medicine, Stem Cells and Transplantation theme. 

Research Interests

My overarching research aim is to understand the mechanisms underlying the impairment in function and survival of pancreatic beta-cells in type 2 diabetes, cells with a critical role in regulating blood glucose homeostasis. I am particularly interested in how glucose sensing impacts on both beta-cell function and survival. My research falls into two main research areas: i) delineating the pathways mediating cell survival. vs death in type 2 diabetes, with a particular focus on autophagy; ii) identifying mechanisms for preserving the metabolic function of beta-cells. These areas are particularly relevant given the loss of beta-cell function and increased cell death evident in type 2 diabetes. 

Current Research

i) Role for autophagy in regulating beta-cell survival – aim is to delineate the complex interplay between apoptosis and autophagy in regulating beta-cell death and to understand how a current therapeutic target for type 2 diabetes (GLP-1) alters this crosstalk.

ii) Impact of glucose sensing on beta-cell autophagy - aim is to determine how glucose sensing impacts on autophagy in the pancreatic beta-cell under conditions mimicking type 2 diabetes.

iii) Understanding the role of cell connectivity in preserving the pancreatic beta-cell phenotype - aim is to identify the role of cell connectivity in preserving appropriate glucose-sensing by the pancreatic beta-cells.

Postgraduate Supervision

I currently supervise 2 PhD students and 3 Masters students.

Esteem Indicators

• Newcastle University Research Fellowship
• Diabetes UK RD Lawrence Fellowship
• EFSD Albert Renold Travel Fellowship
• EMBO Short-Term Travel Fellowship
• Innovators in Diabetes (iDia) programme recipient
  

Funding

• Diabetes UK
• Diabetes Research and Wellness Foundation
• North East Diabetes Trust
• Royal Society
• EFSD
• EMBO
• MRC/Faculty of Medical Sciences PhD studentship
• Wellcome Trust ISSF grant
• Newcastle Healthcare Charity

Undergraduate Teaching

Lecturer/Assessor on PSC2002 Membrane Transport and Cell Signalling in Health and Disease.

Supervision of final year undergraduate student laboratory projects.

Postgraduate Teaching

Programme/module lead and Lecturer/Assessor for MMB8035 Diabetes.

Lecturer/Assessor on MMB8022 Regenerative Medicine and Stem Cells.

Lecturer/Assessor on MMB8050 Therapeutic Applications of Cell Signalling Pathways.

Supervision of MRes and MSci student laboratory projects.

Internal PhD examiner.

• Articles

  • Cornell D, Miwa S, Georgiou M, Anderson SJ, Honkanen-Scott M, Shaw JAM, Arden C. Pseudoislet aggregation of pancreatic β-cells improves glucose stimulated insulin secretion by altering glucose metabolism and increasing ATP production. Cells 2022, 11(15), 2330.
  • Yu X, Arden C, Berlinguer-Palmini R, Chen C, Bradshaw C, Smith AL, Whitehall J, White M, Anderson S, Kattner N, Shaw J, Turnbull D, Greaves LC, Walker M. Mitochondrial complex I subunit deficiency promotes pancreatic α-cell proliferation. Molecular Metabolism 2022, 60, 101489.
  • Thomas P, Arden C, Corcoran J, Hacker C, Welters HJ, Morgan NG. Differential routing and disposition of the long-chain saturated fatty acid palmitate in rodent vs human beta-cells. Nutrition & diabetes 2022, 12, 22. In Preparation.
  • Zummo FP, Krishnanda SI, Georgiou M, O'Harte FPM, Parthsarathy V, Cullen KS, Honkanen-Scott M, Shaw JAM, Lovat PE, Arden C. Exendin-4 stimulates autophagy in pancreatic β-cells via the RAPGEF/EPAC-Ca2+-PPP3/calcineurin-TFEB axis. Autophagy 2021, epub ahead of print.
  • Moonira T, Chachra SS, Ford BE, Marin S, Alshawi A, Adam-Primus NS, Arden C, Al-Oanzi ZH, Foretz M, Viollet B, Cascante M, Agius L. Metformin lowers glucose 6-phosphate in hepatocytes by activation of glycolysis downstream of glucose phosphorylation. Journal of Biological Chemistry 2020, 295(10), 3330-3346.
  • Dhayal S, Zummo FP, Anderson MW, Thomas P, Welters H, Arden C, Morgan PN. Differential effects of saturated and unsaturated fatty acids on autophagy in pancreatic β-cells. Journal of Molecular Endocrinology 2019, 63(4), 285-296.
  • Arden C. A role for Glucagon-Like Peptide-1 in the regulation of β-cell autophagy. Peptides 2018, 100, 85-93.
  • Al-Oanzi ZH, Fountana S, Moonira T, Tudhope SJ, Petrie JL, Alshawi A, Patman G, Arden C, Reeves HL, Agius L. Opposite effects of a glucokinase activator and metformin on glucose-regulated gene expression in hepatocytes. Diabetes, Obesity and Metabolism 2017, 19(8), 1078-1087.
  • Zummo FP, Cullen KS, Honkanen-Scott M, Shaw JAM, Lovat PE, Arden C. Glucagon-like peptide-1 protects pancreatic beta-cells from death by increasing autophagic flux and restoring lysosomal function. Diabetes 2017, 66(5), 1272-1285.
  • Cullen KS, Al-Oanzi ZH, O'Harte FPM, Agius L, Arden C. Glucagon induces translocation of glucokinase from the cytoplasm to the nucleus of hepatocytes by transfer between 6-phosphofructo 2-kinase/fructose 2,6-bisphosphatase-2 and the glucokinase regulatory protein. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 2014, 1843(6), 1123-1134.
  • Petrie JL, Al-Oanzi ZH, Arden C, Tudhope SJ, Mann J, Kieswich J, Yaqoob MM, Towle HC, Agius L. Glucose induces protein targeting to glycogen in hepatocytes by fructose 2,6-bisphosphate-mediated recruitment of MondoA to the promoter. Molecular and Cellular Biology 2013, 33(4), 725-738.
  • Arden C, Tudhope SJ, Petrie JL, Al-Oanzi ZH, Cullen KS, Lange AJ, Towle HC, Agius L. Fructose 2,6-bisphosphate is essential for glucose-regulated genetranscription of glucose-6-phosphatase and other ChREBP target genes inhepatocytes. Biochemical Journal 2012, 443(1), 111-123.
  • Tudhope SJ, Wang CC, Petrie JL, Potts L, Malcomson F, Kieswich J, Yaqoob MM, Arden C, Hampson LJ, Agius L. A Novel Mechanism for Regulating Hepatic Glycogen Synthesis Involving Serotonin and Cyclin-Dependent Kinase-5. Diabetes 2012, 61(1), 49-60.
  • Cullen KS, Matschinsky FM, Agius L, Arden C. Susceptibility of Glucokinase-MODY Mutants to Inactivation by Oxidative Stress in Pancreatic β-Cells. Diabetes 2011, 60(12), 3175-3185.
  • Arden C, Petrie JL, Tudhope SJ, Al-Oanzi Z, Claydon AJ, Beynon RJ, Towle HC, Agius L. Elevated glucose represses liver glucokinase and induces its regulatory protein to safeguard hepatic phosphate homeostasis. Diabetes 2011, 60(12), 3110-3120.
  • Mukhtar MH, Payne VA, Arden C, Harbottle A, Khan S, Lange AJ, Agius L. Inhibition of glucokinase translocation by AMP-activated protein kinase is associated with phosphorylation of both GKRP and 6-phosphofructo-2-kinase/ fructose-2,6-bisphosphatase. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology 2008, 294(3), R766-R774.
  • Arden C, Hampson L, Huang G, Shaw J, Aldibbiat A, Holliman G, Manas D, Khan S, Lange A, Agius L. A role for PFK-2/FBPase-2, as distinct from fructose 2,6-bisphosphate, in regulation of insulin secretion in pancreatic β-cells. Biochemical Journal 2008, 411(1), 41-51.
  • Payne VA, Arden C, Lange AJ, Agius L. Contributions of glucokinase and phosphofructokinase-2/fructose bisphosphatase-2 to the elevated glycolysis in hepatocytes from Zucker fa/fa rats. American Journal of Physiology - Regulatory Integrative and Comparative Physiology 2007, 293(2), R618-R625.
  • Arden C, Trainer A, De La Iglesia N, Scougall KT, Gloyn AL, Lange AJ, Shaw J, Matschinsky FM, Agius L. Cell biology assessment of glucokinase mutations V62M and G72R in pancreatic β-cells: Evidence for cellular instability of catalytic activity. Diabetes 2007, 56(7), 1773-1782.
  • Aiston S, Hampson LJ, Arden C, Iynedjian PB, Agius L. The role of protein kinase B/Akt in insulin-induced inactivation of phosphorylase in rat hepatocytes. Diabetologia 2006, 49(1), 174-182.
  • Arden C, Green AR, Hampson LJ, Aiston S, Harndahl L, Greenberg CC, Brady MJ, Freeman S, Poucher SM, Agius L. Increased sensitivity of glycogen synthesis to phosphorylase-a and impaired expression of the glycogen-targeting protein R6 in hepatocytes from insulin-resistant Zucker fa/fa rats. FEBS Journal 2006, 273(9), 1989-1999.
  • Arden C, Baltrusch S, Agius L. Glucokinase regulatory protein is associated with mitochondria in hepatocytes. FEBS Letters 2006, 580(8), 2065-2070.
  • Hampson LJ, Arden C, Agius L, Ganotidis M, Kosmopoulou MN, Tiraidis C, Elemes Y, Sakarellos C, Leonidas DD, Oikonomakos NG. Bioactivity of glycogen phosphorylase inhibitors that bind to the purine nucleoside site. Bioorganic and Medicinal Chemistry 2006, 14(23), 7835-7845.
  • Payne VA, Arden C, Wu C, Lange AJ, Agius L. Dual role of phosphofructokinase-2/fructose bisphosphatase-2 in regulating the compartmentation and expression of glucokinase in hepatocytes. Diabetes 2005, 54(7), 1949-1957.
  • Arden C, Harboottle A, Baltrusch S, Tiedge M, Agius L. Glucokinase is an integral component of the insulin granules in glucose-responsive insulin secretory cells and does not translocate during glucose stimulation. Diabetes 2004, 53(9), 2346-2352.

• Book Chapter

  • Williams AW, Georgiou MG, Arden CA. Autophagy in the pancreas. In: Rothermel B; Diwan A, ed. Autophagy in Health and Disease. Amsterdam: Elsevier Science, 2021, pp.197-212.

• Review

  • Persaud S, Arden C, Bergsten P, Bone A, Brown J, Dunmore S, Harrison M, Hauge-Evans A, Kelly C, King A, Maffucci T, Marriott C, McClenaghan N, Morgan N, Reers C, Russell M, Turner M, Willoughby E, Younis M, Zhi Z, Jones P. Pseudoislets as primary islet replacements for research: Report on a symposium at King's College London, London UK. Islets 2010, 2(4), 236-239.