Skeletal Muscle Sorbitol Levels in Diabetic Rats with and without Insulin Therapy and Endurance Exercise Training

Sorbitol accumulation is postulated to play a role in skeletal muscle dysfunction associated with diabetes. The purpose of this study was to determine the effects of insulin and of endurance exercise on skeletal muscle sorbitol levels in streptozotocin-induced diabetic rats. Rats were assigned to one experimental group (control sedentary, control exercise, diabetic sedentary, diabetic exercise, diabetic sedentary no-insulin). Diabetic rats received daily subcutaneous insulin. The exercise-trained rats ran on a treadmill (1 hour, 5X/wk, for 12 weeks). Skeletal muscle sorbitol levels were the highest in the diabetic sedentary no-insulin group. Diabetic sedentary rats receiving insulin had similar sorbitol levels to control sedentary rats. Endurance exercise did not significantly affect sorbitol levels. These results indicate that insulin treatment lowers sorbitol in skeletal muscle; therefore sorbitol accumulation is probably not related to muscle dysfunction in insulin-treated diabetic individuals. Endurance exercise did not influence intramuscular sorbitol values as strongly as insulin

Working through whiteness, race and (anti) racism in physical education teacher education

Background: The persistent gaps between a largely white profession and ethnically diverse school populations have brought renewed calls to support teachers' critical engagement with race. Programmes examining the effects of racism have had limited impact on practice, with student teachers responding with either denial, guilt or fear; they also contribute to a deficit view of racialised students in relation to an accepted white ‘norm’, and position white teachers ‘outside’ of race. Recent calls argue for a shift in focus towards an examination of the workings of the dominant culture through a critical engagement with whiteness, positioning white teachers within the processes of racialisation. Teacher educators' roles are central, and yet, while we routinely expect student teachers to reflect critically on issues of social justice, we have been less willing to engage in such work ourselves. This is particularly the case within physical education teacher education (PETE), an overwhelmingly white, embodied space, and where race and racism as professional issues are largely invisible. Purpose: This paper examines the operation of whiteness within PETE through a critical reflection on the three co-authors' careers and experiences working for social justice. The research questions were twofold: How are race, (anti) racism and whiteness constructed through everyday experiences of families, schooling and teacher education? How can collective biography be used to excavate discourses of race, racism and whiteness as the first step towards challenging them? In beginning the process of reflecting on what it means for us ‘to do own work’ in relation to (anti) racism, we examine some of the tensions and challenges for teacher educators in PE attempting to work to dismantle whiteness. Methodology: As co-authors, we engaged in collective biography work – a process in which we reflected upon, wrote about and shared our embodied experiences and memories about race, racism and whiteness as educators working for social justice. Using a critical whiteness lens, these narratives were examined for what they reveal about the collective practices and discourses about whiteness and (anti)racism within PETE. Results: The narratives reveal the ways in which whiteness operates within PETE through processes of naturalisation, ex-denomination and universalisation. We have been educated, and now work within, teacher education contexts where professional discourse about race at best focuses on understanding the racialised ‘other’, and at worse is invisible. By drawing on a ‘racialised other’, deficit discourse in our pedagogy, and by ignoring race in own research on inequalities in PETE, we have failed to disrupt universalised discourses of ‘white-as-norm’, or addressed our own privileged racialised positioning. Reflecting critically on our biographies and careers has been the first step in recognising how whiteness works in order that we can begin to work to disrupt it. Conclusion: The study highlights some of the challenges of addressing (anti)racism within PETE and argues that a focus on whiteness might offer a productive starting point. White teacher educators must critically examine their own role within these processes if they are to expect student teachers to engage seriously in doing the same

Aberrant Cyclization Affords a C-6 Modified Cyclic Adenosine 5′-Diphosphoribose Analogue with Biological Activity in Jurkat T Cells

*S Supporting Information ABSTRACT: Two nicotinamide adenine dinucleotide (NAD +) analogues modified at the 6 position of the purine ring were synthesized, and their substrate properties toward Aplysia californica ADP-ribosyl cyclase were investigated. 6-N-Methyl NAD + (6-N-methyl nicotinamide adenosine 5′-dinucleotide 10) hydrolyzes to give the linear 6-N-methyl ADPR (adenosine 5′-diphosphoribose, 11), whereas 6-thio NHD + (nicotinamide 6-mercaptopurine 5′-dinucleotide, 17) generates a cyclic dinucleotide. Surprisingly, NMR correlation spectra confirm this compound to be the N1 cyclic product 6-thio N1-cIDPR (6-thio cyclic inosine 5′-diphosphoribose, 3), although the corresponding 6-oxo analogue is well-known to cyclize at N7. In Jurkat T cells, unlike the parent cyclic inosine 5′-diphosphoribose N1-cIDPR 2, 6-thio N1-cIDPR antagonizes both cADPR- and N1cIDPR-induced Ca 2+ release but possesses weak agonist activity at higher concentration. 3 is thus identified as the first C-6 modified cADPR (cyclic adenosine 5′-diphosphoribose) analogue antagonist; it represents the first example of a fluorescent N1cyclized cADPR analogue and is a new pharmacological tool for intervention in the cADPR pathway of cellular signaling

Dysregulated Release and Degradation of Insulin During Mononuclear Cell-Induced -Cell Lysis in HIT Cells

Activated human mononuclear cells (MCs) were coincubated for 8 h with HIT cells, a clonal cell line of pancreatic islet β-cells. Measurements of HIT cell viability and insulin secretion were determined to 1) ascertain whether activated MCs can alter β-cells viability in the absence of exogenously provided cytokines, 2) examine this response over a range of MC–HIT cell ratios, and 3) identify mechanisms responsible for altered insulin release consequent to MC-induced HIT cell damage. HIT cell viability was markedly decreased by activated MCs during an 8-h coincubation. HIT cell lysis could be attributed to activated natural killer cells, and lysis did not occur in the presence of activated T-lymphocyte clones. Activated MCs caused a marked early increase in insulin release from HIT cells (increase at 2 h: 7.75 ± 0.16 nM for activated MCs, 2.66 ± 0.09 nM for control; P &amp;lt; 0.001). Insulin levels by the 8th h of the coincubation were significantly lower than the 2-h peak (4.33 ± 0.13 vs. 7.75 ± 0.16 nM, P &amp;lt; 0.001). These changes in insulin were dependent on the ratio of activated MCs to HIT cells with the effects clearly evident at an activated MC–HIT cell ratio of ≥ 10:1. Pretreatment of activated MCs and HIT cells with prostaglandin-synthesis inhibitors did not prevent the cytotoxic effects of activated MCs on HIT cells. Somatostatin did not inhibit the early exaggerated insulin release, suggesting that these increased insulin levels represented leakage of insulin from damaged HIT cells rather than functional insulin secretion. The decrements in insulin levels during the later stages of the experiments were determined by high-performance liquid chromatography to be caused by degradation of previously released insulin. These studies establish that activated MCs cause HIT cell lysis in the absence of exogenously provided cytokines and that HIT cells can be used as targets to examine the functional consequences of exposing pancreatic islet β-cells to activated MCs.</jats:p