Skip to main content

Therapeutic targeting of the proinflammatory IL-6-JAK/STAT signalling pathways responsible for vascular restenosis in Type 2 diabetes mellitus (2019)
Journal Article
Florah, T., Moshapa, , Riches-Suman, K., Palmer, T. M., & Palmer, T. M. (2019). Therapeutic targeting of the proinflammatory IL-6-JAK/STAT signalling pathways responsible for vascular restenosis in Type 2 diabetes mellitus. Cardiology Research and Practice, 2019, doi:10.1155/2019/9846312

Type 2 diabetes mellitus (T2DM) is increasing worldwide, and it is associated with increased risk of coronary artery disease (CAD). For T2DM patients, the main surgical intervention for CAD is autologous saphenous vein grafting. However, T2DM patient... Read More about Therapeutic targeting of the proinflammatory IL-6-JAK/STAT signalling pathways responsible for vascular restenosis in Type 2 diabetes mellitus.

A769662 inhibits insulin-stimulated akt activation in human macrovascular endothelial cells independent of AMP-activated protein kinase (2018)
Journal Article
Strembitska, A., Mancini, S. J., Gamwell, J. M., Palmer, T. M., Baillie, G. S., & Salt, I. P. (2018). A769662 inhibits insulin-stimulated akt activation in human macrovascular endothelial cells independent of AMP-activated protein kinase. International Journal of Molecular Sciences, 19(12), 3886. doi:10.3390/ijms19123886

Protein kinase B (Akt) is a key enzyme in the insulin signalling cascade, required for insulin-stimulated NO production in endothelial cells (ECs). Previous studies have suggested that AMP-activated protein kinase (AMPK) activation stimulates NO synt... Read More about A769662 inhibits insulin-stimulated akt activation in human macrovascular endothelial cells independent of AMP-activated protein kinase.

Canagliflozin inhibits interleukin-1β-stimulated cytokine and chemokine secretion in vascular endothelial cells by AMP-activated protein kinase-dependent and -independent mechanisms (2018)
Journal Article
Mancini, S. J., Boyd, D., Katwan, O. J., Strembitska, A., Almabrouk, T. A., Kennedy, S., …Salt, I. P. (2018). Canagliflozin inhibits interleukin-1β-stimulated cytokine and chemokine secretion in vascular endothelial cells by AMP-activated protein kinase-dependent and -independent mechanisms. Scientific reports, 8(1), doi:10.1038/s41598-018-23420-4

Recent clinical trials of the hypoglycaemic sodium-glucose co-transporter-2 (SGLT2) inhibitors, which inhibit renal glucose reabsorption, have reported beneficial cardiovascular outcomes. Whether SGLT2 inhibitors directly affect cardiovascular tissue... Read More about Canagliflozin inhibits interleukin-1β-stimulated cytokine and chemokine secretion in vascular endothelial cells by AMP-activated protein kinase-dependent and -independent mechanisms.

Interaction of suppressor of cytokine signalling 3 with cavin-1 links SOCS3 function and cavin-1 stability (2018)
Journal Article
Williams, J. J., Alotaiq, N., Mullen, W., Burchmore, R., Liu, L., Baillie, G. S., …Palmer, T. M. (2018). Interaction of suppressor of cytokine signalling 3 with cavin-1 links SOCS3 function and cavin-1 stability. Nature communications, 9(1), doi:10.1038/s41467-017-02585-y

Effective suppression of JAK–STAT signalling by the inducible inhibitor “suppressor of cytokine signalling 3” (SOCS3) is essential for limiting signalling from cytokine receptors. Here we show that cavin-1, a component of caveolae, is a functionally... Read More about Interaction of suppressor of cytokine signalling 3 with cavin-1 links SOCS3 function and cavin-1 stability.

Linking energy sensing to suppression of JAK-STAT signalling: A potential route for repurposing AMPK activators? (2017)
Journal Article
Speirs, C., Williams, J. J. L., Riches, K., Salt, I. P., & Palmer, T. M. (2018). Linking energy sensing to suppression of JAK-STAT signalling: A potential route for repurposing AMPK activators?. Pharmacological research : the official journal of the Italian Pharmacological Society, 128, 88-100. doi:10.1016/j.phrs.2017.10.001

Exaggerated Janus kinase-signal transducer and activator of transcription (JAK-STAT) signalling is key to the pathogenesis of pro-inflammatory disorders, such as rheumatoid arthritis and cardiovascular diseases. Mutational activation of JAKs is also... Read More about Linking energy sensing to suppression of JAK-STAT signalling: A potential route for repurposing AMPK activators?.

Protein kinase C phosphorylates AMP-Activated protein kinase α1 Ser487 (2016)
Journal Article
Heathcote, H. R., Mancini, S. J., Strembitska, A., Jamal, K., Reihill, J. A., Palmer, T. M., …Salt, I. P. (2016). Protein kinase C phosphorylates AMP-Activated protein kinase α1 Ser487. Biochemical Journal, 473(24), 4681-4697. doi:10.1042/BCJ20160211

The key metabolic regulator, AMP-activated protein kinase (AMPK), is reported to be down-regulated in metabolic disorders, but the mechanisms are poorly characterised. Recent studies have identified phosphorylation of the AMPKα1/α2 catalytic subunit... Read More about Protein kinase C phosphorylates AMP-Activated protein kinase α1 Ser487.

Activation of AMP-activated protein kinase rapidly suppresses multiple pro-inflammatory pathways in adipocytes including IL-1 receptor-associated kinase-4 phosphorylation (2016)
Journal Article
Mancini, S. J., White, A. D., Bijland, S., Rutherford, C., Graham, D., Richter, E. A., …Salt, I. P. (2017). Activation of AMP-activated protein kinase rapidly suppresses multiple pro-inflammatory pathways in adipocytes including IL-1 receptor-associated kinase-4 phosphorylation. Molecular and Cellular Endocrinology, 440, 44-56. doi:10.1016/j.mce.2016.11.010

Inflammation of adipose tissue in obesity is associated with increased IL-1β, IL-6 and TNF-α secretion and proposed to contribute to insulin resistance. AMP-activated protein kinase (AMPK) regulates nutrient metabolism and is reported to have anti-in... Read More about Activation of AMP-activated protein kinase rapidly suppresses multiple pro-inflammatory pathways in adipocytes including IL-1 receptor-associated kinase-4 phosphorylation.

Phosphorylation of Janus kinase 1 (JAK1) by AMP-activated protein kinase (AMPK) links energy sensing to anti-inflammatory signaling (2016)
Journal Article
Rutherford, C., Speirs, C., Williams, J. J., Ewart, M. A., Mancini, S. J., Hawley, S. A., …Palmer, T. M. (2016). Phosphorylation of Janus kinase 1 (JAK1) by AMP-activated protein kinase (AMPK) links energy sensing to anti-inflammatory signaling. Science Signaling, 9(453), ra109. doi:10.1126/scisignal.aaf8566

Adenosine 5′-monophosphate–activated protein kinase (AMPK) is a pivotal regulator of metabolism at cellular and organismal levels. AMPK also suppresses inflammation. We found that pharmacological activation of AMPK rapidly inhibited the Janus kinase... Read More about Phosphorylation of Janus kinase 1 (JAK1) by AMP-activated protein kinase (AMPK) links energy sensing to anti-inflammatory signaling.

The future of EPAC-targeted therapies: Agonism versus antagonism (2015)
Journal Article
Parnell, E., Palmer, T. M., & Yarwood, S. J. (2015). The future of EPAC-targeted therapies: Agonism versus antagonism. Trends in Pharmacological Sciences, 36(4), 203-214. doi:10.1016/j.tips.2015.02.003

Pharmaceutical manipulation of cAMP levels exerts beneficial effects through the regulation of the exchange protein activated by cAMP (EPAC) and protein kinase A (PKA) signalling routes. Recent attention has turned to the specific regulation of EPAC... Read More about The future of EPAC-targeted therapies: Agonism versus antagonism.

Regulation of cell survival by sphingosine-1-phosphate receptor S1P 1 via reciprocal ERK-dependent suppression of Bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1 (2013)
Journal Article
Rutherford, C., Childs, S., Ohotski, J., McGlynn, L., Riddick, M., MacFarlane, S., …Palmer, T. M. (2013). Regulation of cell survival by sphingosine-1-phosphate receptor S1P 1 via reciprocal ERK-dependent suppression of Bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1. Cell Death and Disease, 4(11), doi:10.1038/cddis.2013.455

Although the ability of bioactive lipid sphingosine-1-phosphate (S1P) to positively regulate anti-apoptotic/pro-survival responses by binding to S1P1 is well known, the molecular mechanisms remain unclear. Here we demonstrate that expression of S1P1... Read More about Regulation of cell survival by sphingosine-1-phosphate receptor S1P 1 via reciprocal ERK-dependent suppression of Bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1.


;