Interleukin-1ß activates a short STAT-3 isoform in clonal insulin-secreting cells

Abstract Interleukin-1ß (IL-1ß) is a potent inflammatory cytokine involved in type 1 diabetes and acts through defined IL-1ß signaling pathways. In the present work we describe induction of DNA binding activity to signal transducer and activator of transcription (STAT) in response to IL-1ß in clonal insulin-secreting cells. Moreover, IL-1ß activates a short isoform of STAT-3 that potently stimulates transcription. Immunopre- cipitation studies reveal an interaction between the activated STAT-3 and the IL-1 receptor accessory protein indicating an association between the two signaling pathways. This may be a novel point of transduction cross talk and an additional mechanism utilised by IL-1ß in the pancreatic ß-cell during the process of type 1 diabetes. z 1999 Federation of European Biochemical Societies

Reduced maximum capacity of glycolysis in brown adipose tissue of genetically obese, diabetic (db/db) mice and its restoration following treatment with a thermogenic β-adrenoceptor agonist

AbstractThe maximal activities of the key glycolytic enzymes hexokinase and 6-phosphofructokinase, were reduced in brown adipose tissue in db/db mice compared to their lean littermates. Treatment of db/db mice with the thermogenic β-adrenoceptor agonist, BRL 26830, restored normoglycaemia. The only significant increase in activity of hexokinase and 6-phosphofructokinase in the BRL 26830-treated db/db mice occurred in brown adipose tissue where the total tissue activity increased 10- and 11-fold respectively. These changes together with increased 2-deoxyglucose uptake in vivo suggest that brown adipose tissue can play a quantitatively important role in the removal of glucose from the blood

Leptin signalling in pancreatic islets and clonal insulin-secreting cells

Leptin is a cytokine secreted from adipose tissue at a rate commensurate with the size of the body's fat stores. In addition to its anorectic and thermogenic central actions, leptin is known to act on peripheral tissues, including the pancreatic ß-cell where it inhibits insulin secretion and reduces insulin transcript levels. However, the role of leptin signalling through its full-length receptor, OB-Rb, in the ß-cell remains unclear. In the present study, we show that leptin activates a signal transducer and activator of transcription (STAT)3 signalling mechanism in pancreatic islets and in a rat model of the pancreatic ß-cell, RINm5F. Leptin induced DNA binding to a STAT consensus oligonucleotide and resulted in transcriptional activation from STAT reporter constructs in a manner consistent with STAT3 activation. Western blot analysis confirmed activation of STAT3 in RINm5F and isolated rat islets. Conditions that mimic increased metabolic activity resulted in attenuation of leptin-mediated STAT DNA binding but had no significant eVect on STAT3 tyrosine phosphorylation in RINm5F cells. In addition, leptin activated the mitogen activated protein (MAP) kinase pathway in RINm5F cells. The present study provides a framework for OB-Rb signalling mechanisms in the programming of the ß-cell by leptin and suggests that increased metabolic activity may modulate this function

Interleukin-1ß activates a short STAT-3 isoform in clonal insulin-secreting cells

Abstract Interleukin-1ß (IL-1ß) is a potent inflammatory cytokine involved in type 1 diabetes and acts through defined IL-1ß signaling pathways. In the present work we describe induction of DNA binding activity to signal transducer and activator of transcription (STAT) in response to IL-1ß in clonal insulin-secreting cells. Moreover, IL-1ß activates a short isoform of STAT-3 that potently stimulates transcription. Immunopre- cipitation studies reveal an interaction between the activated STAT-3 and the IL-1 receptor accessory protein indicating an association between the two signaling pathways. This may be a novel point of transduction cross talk and an additional mechanism utilised by IL-1ß in the pancreatic ß-cell during the process of type 1 diabetes. z 1999 Federation of European Biochemical Societies

Health risks, preventive behaviours and respiratory illnesses at the 2019 arbaeen: Implications for covid-19 and other pandemics

COVID-19 poses grave challenges for mass gatherings. One of the world's largest annual gatherings, Arbaeen, occurs in Iraq. We studied respiratory symptoms and risk and protective factors using representative sampling of Arbaeen pilgrims in 2019 to inform prevention of COVID-19 transmission. Structured sampling was used to recruit walking pilgrims. A questionnaire asked about respiratory symptoms, risk, and preventive factors, including hygiene-related resources of toilet facilities. The commonest symptom reported by the 1842 participants (63.3% male, 36.7% fe-male) was cough (25.6%). Eating in mawkibs (rest areas) with indoor kitchens and drinking only packaged water were associated with lower risk of cough (AOR = 0.72, CI = 0.56-0.94; AOR = 0.60; CI = 0.45-0.78, p < 0.05). Facemask use was associated with increased risk of cough (AOR = 2.71, CI = 2.08-3.53, p < 0.05). Handwashing was not protective against cough, or against (one or more of) cough, fever, or breathlessness in multivariate analysis. Toilet facilities often lacked running water (32.1%) and soap (26.1%), and had shared hand towels (17%). To reduce risk of respiratory infections including COVID-19 during Arbaeen or other mass gatherings, needs include running water, soap, and hygienic hand drying options or hand sanitiser. Education on proper handwashing and facemask approaches and monitoring around food preparation and eating spaces are needed