SGK1 activity in Na+ absorbing airway epithelial cells monitored by assaying NDRG1-Thr(346/356/366) phosphorylation

Studies of HeLa cells and serum- and glucocorticoid-regulated kinase 1 (SGK1) knockout mice identified threonine residues in the n-myc downstream-regulated gene 1 protein (NDRG1-Thr(346/356/366)) that are phosphorylated by SGK1 but not by related kinases (Murray et al., Biochem J 385:1-12, 2005). We have, therefore, monitored the phosphorylation of NDRG1-Thr(346/356/366) in order to explore the changes in SGK1 activity associated with the induction and regulation of the glucocorticoid-dependent Na+ conductance (G (Na)) in human airway epithelial cells. Transient expression of active (SGK1-S422D) and inactive (SGK1-K127A) SGK1 mutants confirmed that activating SGK1 stimulates NDRG1-Thr(346/356/366) phosphorylation. Although G (Na) is negligible in hormone-deprived cells, these cells displayed basal SGK1 activity that was sensitive to LY294002, an inhibitor of 3-phosphatidylinositol phosphate kinase (PI3K). Dexamethasone (0.2 mu M) acutely activated SGK1 and the peak of this response (2-3 h) coincided with the induction of G (Na), and both responses were PI3K-dependent. While these data suggest that SGK1 might mediate the rise in G (Na), transient expression of the inactive SGK1-K127A mutant did not affect the hormonal induction of G (Na) but did suppress the activation of SGK1. Dexamethasone-treated cells grown on permeable supports formed confluent epithelial sheets that generated short circuit current due to electrogenic Na+ absorption. Forskolin and insulin both stimulated this current and the response to insulin, but not forskolin, was LY294002-sensitive and associated with the activation of SGK1. While these data suggest that SGK1 is involved in the control of G (Na), its role may be minor, which could explain why sgk1 knockout has different effects upon different tissues.

N-terminally modified glucagon-like peptide-1(7-36) amide exhibits resistance to enzymatic degradation while maintaining its antihyperglycaemic activity in vivo

Glucagon-like peptide-1 (7-36)amide (tGLP-1) is inactivated by dipeptidyl peptidase (DPP) IV by removal of the NH2-terminal dipeptide His(7)-Ala(8). We examined the degradation of NH2-terminally modified His(7)-glucitol tGLP-1 and its insulin-releasing and antihyperglycaemic activity in vivo, tGLP-1 was degraded by purified DPP IV after 4 h (43% intact) and after 12 hi 89% was converted to GLP-1(9-36)amide. In contrast > 99% of His(7)-glucitol tGLP-1 remained intact at 12 h. His(7)-glucitol tGLP-1 was similarly resistant to plasma degradation in vitro. His7-glucitol tGLP-1 showed greater resistance to degradation in vivo (92% intact) compared to tGLP-1 (27% intact) 10 min after i.p. administration to Wistar rats. Glucose homeostasis was examined following i.p. injection of both peptides (12 nmol/kg) together with glucose (18 mmol/kg). Plasma glucose concentrations were significantly reduced and insulin concentrations elevated following peptides administration compared with glucose alone. The area under the curve (AUC) for glucose for controls (AUC 691 +/- 35 mM/min) was significantly lower after administration of tGLP-1 and His7-glucitol tGLP-1 (36 and 49% less; AUC; 440 +/- 40 and 353 +/- 31 mM/min, respectively; P

Research intensity and knowledge transfer activity in UK universities

As the innovation process has become more open and networked, Government policy in the UK has sought to promote both research excellence in the university sector and the translation of this into economic benefit through university–business engagement. However, this policy approach has tended to be applied uniformly with little account for organisational differences within the sector. In this paper we consider if differences between universities in their research performance is reflected in their knowledge transfer activity. Specifically, as universities develop a commercialization agenda are the strategic priorities for knowledge transfer, the organisational supports in place to facilitate knowledge transfer and the scale and scope of knowledge transfer activity different for high research intensive (HRI) and low research intensive (LRI) universities? The findings demonstrate that universities’ approach to knowledge transfer is shaped by institutional and organisational resources, in particular their ethos and research quality, rather than the capability to undertake knowledge transfer through a Technology Transfer Office (TTO). Strategic priorities for knowledge transfer are reflected in activity, in terms of the dominance of specific knowledge transfer channels, the partners with which universities engage and the geography of business engagement.