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, 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 my colleagues Professor Susan Ozanne (Early life programming of insulin action, funded by BBSRC) and Drs Robert Semple and Gemma Brierley (Therapeutic applications of anti-insulin receptor antibodies, funded by Diabetes UK).
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.
Le, H.T.T., Sorrell, A.M. & Siddle, K. (2012) Two isoforms of the mRNA binding protein IGF2BP2 are generated by alternative translational initiation. PLoS One, 7(3):e33140. PMID: 22427968. PMCID: PMC3299737.
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
Siddle K. (2011) Signalling by insulin and IGF receptors: supporting acts and new players. J Mol Endocrinol, 47(1):R1-10. PMID: 21498522.
Spriggs KA, Cobbold LC, Ridley SH, Coldwell M, Bottley A, Bushell M, Willis AE, Siddle K. (2009). The human insulin receptor mRNA contains a functional internal ribosome entry segment. Nucleic Acids Res, 37(17):5881-93. PMID: 19654240. PMCID: PMC2761284.
Boyle KB, Hadaschik D, Virtue S, Cawthorn WP, Ridley SH, O’Rahilly S, Siddle K. (2009). The transcription factors Egr1 and Egr2 have opposing influences on adipocyte differentiation. Cell Death Differ, 16(5):782-9. PMID: 19229250. PMCID: PMC2670277.
Surinya KH, Forbes BE, Occhiodoro F, Booker GW, Francis GL, Siddle K, Wallace JC, Cosgrove LJ. (2008). An investigation of the ligand binding properties and negative cooperativity of soluble insulin-like growth factor receptors. J Biol Chem, 283(9):5355-63. PMID: 18056713.
Benyoucef S, Surinya K.H, Hadaschik D & Siddle, K. (2007) Characterisation of insulin/IGF hybrid receptors: contributions of the insulin receptor L2 and Fn1 domains and the alternatively spliced exon 11 sequence to ligand binding and receptor activation. Biochem J, 403(3):603-13. PMID: 17291192. PMCID: PMC1876384.
Holt, L.J. & Siddle, K. (2005) Grb10 and Grb14: enigmatic regulators of insulin action – and more? Biochem. J. 388(2):393-406. PMID: 15901248. PMCID: PMC1138946