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Jay S. Skyler
Investigators, patients and their families, and the public all wish for research to advance, to enable us to prevent or cure human type 1 diabetes. There has been much progress towards potentially achieving this; yet, there are a number of issues associated with conducting and reporting studies in this area. In this issue, Jay Skyler ( https://doi.org/10.1007/s00125-017-4530-x) reviews how the reporting of research findings creates hope amongst patients. Sadly, headlines often overstate results and give hype to advances that are but one small step on the road to achievement of a clinically meaningful outcome. It is important to recognise the limitations of studies, such as those conducted in rodent models, and even pilot studies conducted in human beings. The entire scientific enterprise (investigators, funders, journal editors) collectively need to take responsibility for tempered and realistic reporting. Significant progress is being made, however, and with time, will result in clinically useful approaches to preventing and/or curing type 1 diabetes. The figures from this review are available as a downloadable slideset.
Giuseppe Mancia, Guido Grassi
Thierry Alquier, Vincent Poitout
The advent of gene-targeting strategies in mice has enabled scientists to study the biological function and pathological role of genes implicated in metabolic physiology. However, metabolic phenotyping of pharmacological mouse models is not trivial and can be profoundly influenced by numerous methodological and genetic variables. In this issue, Alquier and Poitout ( https://doi.org/10.1007/s00125-017-4495-9) review the most commonly used experimental tests to assess glucose and energy homeostasis in mice. They also provide some guidelines regarding the design, analysis and interpretation of these tests and identify important caveats and confounding factors that must be taken into account when drawing conclusions from the findings generated. In the context of the current reproducibility debate in biomedical sciences, this review also emphasises the importance of reporting methods accurately and transparently, acknowledging limitations and pitfalls, as well as reproducing the findings using complementary approaches. The figure from this review is available as a downloadable slide.
Alexandra Coomans de Brachène, Reinaldo S. Dos Santos, Laura Marroqui, Maikel L. Colli, Lorella Marselli, Raghavendra G. Mirmira, Piero Marchetti, Decio L. Eizirik
IFN-α, a cytokine present in islets of individuals with type 1 diabetes, plays a key role in the pathogenesis of diabetes. IFN-α upregulates islet inflammation, endoplasmic reticulum (ER) stress and MHC class I overexpression. Furthermore, it may contribute to presentation of beta cell autoantigens. In this issue, Coomans de Brachène and Dos Santos et al ( https://doi.org/10.1007/s00125-017-4536-4) report that IFN-α-induced expression of inflammatory and ER stress markers in human beta cells returned to baseline after 24–48 h following removal of the cytokine, while MHC class I overexpression at the cell surface persisted for at least 7 days. Pretreatment with Janus kinase (JAK) inhibitors (mediators of IFN-α signalling) prevented IFN-α-induced MHC class I overexpression but, when added 24 h after IFN-α exposure, JAK inhibitors did not accelerate the return of MHC class I levels to baseline following IFN-α removal. These findings suggest that JAK inhibitors may protect beta cells in type 1 diabetes, but that these agents probably need to be introduced ahead of the clinical onset of disease.
Joana F. Sacramento, Daniel J. Chew, Bernardete F. Melo, Matteo Donegá, Wesley Dopson, Maria P. Guarino, Alison Robinson, Jesus Prieto-Lloret, Sonal Patel, Bradley J. Holinski, Nishan Ramnarain, Victor Pikov, Kristoffer Famm, Silvia V. Conde
The carotid body, an organ classically defined as an oxygen sensor, regulates peripheral insulin sensitivity and glucose homeostasis, representing a novel therapeutic target for metabolic diseases. Surgical resection of the carotid body or of its sensitive nerve, the carotid sinus nerve (CSN), has been tested as a therapeutic approach for carotid body-mediated diseases. However, this procedure is prone to cause side effects. In this issue, Sacramento and Chew et al ( https://doi.org/10.1007/s00125-017-4533-7) report that bioelectronic neuromodulation of the CSN by kilohertz frequency alternating current (KHFAC) restores insulin sensitivity and glucose tolerance in a rat model of type 2 diabetes. Additionally, the authors show that KHFAC neuromodulation of the CSN is reversible. These findings indicate that a bioelectronic medicine approach could bring significant improvements to care for type 2 diabetes, providing long-term glucose control and avoiding systemic effects, with negligible interference with daily activities. Thus, it is suggested that if these findings can be repeated in human studies, there is potential for this therapy to result in high treatment adherence and increased quality of life for individuals with metabolic diseases.
All text supplied by the authors.