Research Perspective Volume 2, Issue 9 pp 621—626

Figure 1. Insulin-like signalling plays a central role in growth, metabolism and the aging process. Insulin, derived from pancreatic beta-cells in mammals or insulin-like peptides derived from neuroendocrine cells in invertebrates signals via binding to and activation of the membrane bound receptors. This event subsequently activates PI3K, which through phosphorylation of membrane lipids (phosphorinositides) regulates activity of the downstream kinase AKT. AKT eventually phosphorylates forkhead transcript-tion factors such as FOXO1, which are then exported from the nucleus and degraded. FOXOs regulate transcription of many genes involved in glucose and lipid metabolism, growth, stress response and the aging process. Thus, insulin-like signalling is able to control all of these processes through FOXO regulation and other signalling cascades, in the end impinging on crucial physiological processes and lifespan itself. Nonetheless, chronic intake of energy-dense food coupled with little physical activity leads to hyperlipidemia and hyperglycemia, which through several mechanisms (including JNK1 activation) reduce cellular insulin sensitivity, thereby disrupting metabolic homeostasis.