Hepatic JAK2 protects against atherosclerosis through circulating IGF-1.

Atherosclerosis is considered both a metabolic and inflammatory disease; however, the specific tissue and signaling molecules that instigate and propagate this disease remain unclear. The liver is a central site of inflammation and lipid metabolism that is critical for atherosclerosis, and JAK2 is a key mediator of inflammation and, more recently, of hepatic lipid metabolism. However, precise effects of hepatic Jak2 on atherosclerosis remain unknown.

FAK signalling controls insulin sensitivity through regulation of adipocyte survival.

Focal adhesion kinase (FAK) plays a central role in integrin signalling, which regulates growth and survival of tumours. Here we show that FAK protein levels are increased in adipose tissue of insulin-resistant obese mice and humans. Disruption of adipocyte FAK in mice or in 3T3 L1 cells decreases adipocyte survival.

JAK2 promotes brown adipose tissue function and is required for diet- and cold-induced thermogenesis in mice.

Aims/hypothesis: Non-shivering thermogenesis in adipose tissue can be activated by excessive energy intake or following cold exposure. The molecular mechanisms regulating this activation have not been fully elucidated. The Janus kinase (JAK) - signal transducer and activator of transcription (STAT) pathway mediates the signal transduction of numerous hormones and growth factors that regulate adipose tissue development and function, and may play a role in adaptive thermogenesis.

Overexpression of HIF-2α in pancreatic β cells does not alter glucose homeostasis.

Both type 1 and type 2 diabetes are associated with insufficient functional β-cell mass. Understanding intracellular signaling pathways associated with this decline is important in broadening our understanding of the disease and potential therapeutic strategies. The hypoxia inducible factor pathway (HIF) plays a critical role in cellular adaptation to hypoxic conditions.

Rb and p107 are required for alpha cell survival, beta cell cycle control and glucagon-like peptide-1 action.

Aims/hypothesis: Diabetes mellitus is characterised by beta cell loss and alpha cell expansion. Analogues of glucagon-like peptide-1 (GLP-1) are used therapeutically to antagonise these processes; thus, we hypothesised that the related cell cycle regulators retinoblastoma protein (Rb) and p107 were involved in GLP-1 action.

Methods: We used small interfering RNA and adenoviruses to manipulate Rb and p107 expression in insulinoma and alpha-TC cell lines.

Adipocyte-specific deficiency of Janus kinase (JAK) 2 in mice impairs lipolysis and increases body weight, and leads to insulin resistance with ageing.

Aims/hypothesis: The growing obesity epidemic necessitates a better understanding of adipocyte biology and its role in metabolism. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway mediates signalling by numerous cytokines and hormones that regulate adipocyte function, illustrating the physiological importance of adipose JAK-STAT. The aim of this study was to investigate potential roles of adipocyte JAK2, an essential player in the JAK-STAT pathway, in adipocyte biology and metabolism.

Sodium arsenite and cadmium chloride induction of proteasomal inhibition and HSP accumulation in Xenopus laevis A6 kidney epithelial cells.

Sodium arsenite (NA) and cadmium chloride (CdCl(2)) are relatively abundant environmental toxicants that have multiple toxic effects including carcinogenesis, dysfunction of gene regulation and DNA and protein damage. In the present study, treatment of Xenopus laevis A6 kidney epithelial cells with concentrations of NA (20-30 μM) or CdCl(2) (100-200 μM) that induced HSP30 and HSP70 accumulation also produced an increase in the relative levels of ubiquitinated protein. Actin protein levels were unchanged in these experiments.