Mechanism of action of insulin and insulin-like growth factors
I am interested in the receptors and signalling pathways that mediate the actions of insulin and IGFs, particularly molecular mechanisms underlying insulin/IGF signalling specificity and regulatory pathways impacting on insulin/IGF sensitivity. Latterly my group worked on aspects of receptor structure, particularly determinants of ligand binding affinity and specificity, the function of insulin/IGF hybrid receptors, and the regulatory effects of insulin/IGFs on gene transcription. I formally retired from my University position in September 2014 but retain active research interests in collaboration with colleagues: Professor Robert Semple (now in Edinburgh) and Dr Gemma Brierley (Therapeutic applications of anti-insulin receptor antibodies) and Professor Susan Ozanne (Early life programming of insulin action).
Brierley GV, Webber H, Rasijeff E, Grocott, S, Siddle K, Semple RK (2020) Anti-Insulin receptor antibodies improve hyperglycemia in a mouse model of human insulin receptoropathy. Diabetes 69(11): 2481-2489. PMID: 32816962. PMCID: PMC7576564
Brierley GV, Siddle K, Semple RK (2018) Evaluation of anti-insulin receptor antibodies as potential novel therapies for human insulin receptoropathy using cell culture models. Diabetologia 61(7): 1662-1675. PMID: 29700562. PMCID: PMC6445487
Groeneveld, M.P., Brierley, G.V., Rocha, N.M., Siddle, K. & Semple, R.K. (2016) Acute knockdown of the insulin receptor or its substrates Irs1 and 2 in 3T3-L1 adipocytes suppresses adiponectin production. Sci Rep, 6:21105. PMID: 26888756. PMCID: PMC4758029.
Martin-Gronert MS, Fernandez-Twinn DS, Bushell M, Siddle K, Ozanne SE. (2016) Cell-autonomous programming of rat adipose tissue insulin signalling proteins by maternal nutrition. Diabetologia, 59(6): 1266-75. PMID: 26965244. PMCID: PMC4861755.
Siddle, K. (2012) Molecular basis of signaling specificity of insulin and IGF receptors: neglected corners and recent advances. Front Endocrinol, 3:34. PMID: 22649417.PMCID: PMC3355962.
Ferland-McCollough, D., Fernandez-Twinn, D.S., Cannell, I.G., David, H., Warner, M., Vaag, A.A., Bork-Jensen, J., Brøns, C., Gant, T.W., Willis, A.E., Siddle, K., Bushell, M. & Ozanne, S.E. (2012) Programming of miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes. Cell Death Differ, 19(6): 1003-12. PMID: 22223106. PMCID: PMC3354052