English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Insulin-like growth factors (IGFs) are, besides other mechanisms, controlled by growth hormone (GH) secretion and there are at least two different IGFs: IGF-1 and IGF-2. IGFs regulate various cellular processes e.g. survival, differentiation and proliferation (McMorris et al. 1986; McMorris & Dubois-Dalcq 1988; Mozell & McMorris 1991). Growth hormone, which induces IGF-1 secretion from the liver, is generated in the anterior pituitary and regulated by the hypothalamus via growth hormone releasing hormone (GHRH) and growth hormone inhibiting hormone (GHIH) (Jansson et al., 1985; Carlsson & Jansson 1990). IGFs in the brain are synthesised de novo or transported across the blood brain barrier (BBB) and seem to induce a variety of effects on the central nervous system (CNS). So far, the exact transport mechanisms of IGFs into the brain are not fully understood (Duffy, Pardridge, and Rosenfeld 1988). In the rodent brain, IGF-1 is mainly expressed in neuron-dense regions like the hippocampus, striatum, thalamus, hypothalamus and olfactory bulb (Rotwein et al. 1988; Bondy et al. 1990; Garcia-Segura et al. 1991). Accordingly, the insulin-like growth factor-1 receptors (IGF-1Rs) are mainly found in the olfactory bulb, cerebellar cortex and granule cell layer of the dentate gyrus (Rotwein et al. 1988; Bondy et al. 1990; Bondy and Lee 1993; Werther et al. 1990). However, the function of IGF-1R mediated signals in the central nervous system (CNS) is still under investigation. After binding of IGF-1 to the IGF-1R, a signalling cascade is activated which leads to recruitment and subsequently phosphorylation of intracellular adaptor proteins, the so called insulin receptor substrates (IRS) (Jacobs et al. 1983; Rubin et al., 1983; Sun et al. 1991; Lavan et al. 1997; Lavan et al., 1997). Via these adaptor proteins, the MAP kinase (MAPK, mitogen activated protein kinase) cascade, as well as the phosphatidylinositide(PI)3-kinase signalling pathway, is turned on leading to protein kinase B (PKB/AKT) activation, which phosphorylates forkhead box O transcription factors (FoxO) causing their nuclear export (Stokoe et al. 1997; Alessi et al. 1996; Partridge & Bruning 2008). FoxO mediated transcription is involved in cell proliferation, differentiation and oxidative stress defence (Clark et al. 1993; Brunet et al. 1999; Dijkers et al. 2000; Dijkers, Medema, Pals et al. 2000; Medema et al. 2000) suggesting a function of FoxO during development and cellular stress response.

Role of Central Insulin-Like Growth Factor-1 Receptor Signalling in Ageing and Endocrine Regulation