Insulin and IGF Analogues for Targeted Modulation of Metabolic and Mitogenic Signalling

Our research group is interested in all aspects of the physiology of the insulin and IGF-1 and IGF-2 system. Insulin-like hormones share similar 3D structures, and together with their cell membrane receptors — two isoforms of the insulin receptor (IR-A and IR-B), IGF-1 receptor (IGF-1R), IGF-2 receptor (IGF-2R or CI-M6PR), IGF-binding proteins (IGFBPs), and specific proteinases (pappalysins) —form a complex protein network that plays a central role in regulating metabolic homeostasis, development, growth, healing, and lifespan. Insulin and IGFs cross-bind to their receptors with different affinities, triggering distinct but overlapping physiological effects — predominantly metabolic for insulin and mitogenic for IGFs. Dysregulation of these processes can lead to diseases such as diabetes, cancer, and neurological or growth-related disorders. Our primary goal is to understand the structural basis for the different cellular responses — metabolic and mitogenic —elicited by insulin and IGFs. We synthesize hormone analogues, peptide mimetics and pappalysins inhibitors to study their physiological effects and develop new therapeutic candidates for treating diabetes, cancer, and neurological diseases.