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Metabolic disease is caused by a combination of genetic and environmental factors, yet few studies have examined how these factors influence signal transduction, a key mediator of metabolism. Using mass spectrometry-based phosphoproteomics, we quantified 23,126 phosphosites in skeletal muscle of five genetically distinct mouse strains in two dietary environments, with and without acute in vivo insulin stimulation. Almost half of the insulin-regulated phosphoproteome was modified by genetic background on an ordinary diet, and high-fat high-sugar feeding affected insulin signalling in a strain-dependent manner. Our data revealed coregulated subnetworks within the insulin signalling pathway, expanding our understanding of the pathway's organisation. Furthermore, associating diverse signalling responses with insulin-stimulated glucose uptake uncovered regulators of muscle insulin responsiveness, including the regulatory phosphosite S469 on Pfkfb2, a key activator of glycolysis. Finally, we confirmed the role of glycolysis in modulating insulin action in insulin resistance. Our results underscore the significance of genetics in shaping global signalling responses and their adaptability to environmental changes, emphasising the utility of studying biological diversity with phosphoproteomics to discover key regulatory mechanisms of complex traits. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Prescribing of antidepressant and antipsychotic drugs in general populations has increased in the United Kingdom, but prescribing trends in people with type 2 diabetes (T2D) have not previously been investigated. The aim of this study was to describe time trends in annual prevalence of antidepressant and antipsychotic drug prescribing in adult patients with T2D.We conducted repeated annual cross‐sectional analysesof a population‐based diabetes registry with 99% coverage, derived from primary and secondary care data in Scotland, from 2004 to 2021. For each cross‐sectional calendar year time period, we calculated the prevalence of antidepressant and antipsychotic drug prescribing, overall and by sociodemographic characteristics and drug subtype.The number of patients with a T2D diagnosis in Scotland increased from 161 915 in 2004 to 309 288 in 2021. Prevalence of antidepressant and antipsychotic prescribing in patients with T2D increased markedly between 2004 and 2021 (from 20.0 per 100 person‐years to 33.3 per 100 person‐years and from 2.8 per 100 person‐years to 4.7 per 100 person‐years, respectively). We observed this pattern for all drug subtypes except for first‐generation antipsychotics, prescribing of which remained largely stable. The degree of increase, as well as the overall prevalence of prescribing, differed by age, sex, socioeconomic status and subtype of drug class.There has been a marked increase in the prevalence of antidepressant and antipsychotic prescribing in patients with T2D in Scotland. Further research should identify the reasons for this increase, including indication for use and the extent to which this reflects increases in incident prescribing rather than increased duration. [ABSTRACT FROM AUTHOR]

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In 'VIII: clinical approaches', authors address the following themes: 'Evaluation, diagnosis and management I--toward a working diagnosis', 'Evaluation, diagnosis and management II--process steps', 'Interweaving integrative medicine and family medicine', 'Halfway--the art of clinical judgment', 'Seamless integration in family medicine--team-based care', 'Technology--uncovering stories from noise' and 'Caring for patients with multiple long-term conditions'. May readers recognise in these essays the uniqueness of a family medicine approach to care. [ABSTRACT FROM AUTHOR]