Breaking barriers in obesity research: 3D models of dysfunctional adipose tissue.

Obesity is a global health crisis characterised by excessive accumulation of adipose tissue (AT). Under obesogenic conditions, this metabolically active tissue undergoes fibrosis and inflammation, leading to obesity-linked comorbidities. Modelling AT is essential for understanding its pathophysiology and developing treatments to protect against metabolic complications.

The vagus nerve mediates the physiological but not pharmacological effects of PYY on food intake.

Peptide YY (PYY) is a post-prandially released gut hormone with potent appetite-reducing activity, the mechanism of action of which is not fully understood. Unravelling how this system physiologically regulates food intake may help unlock its therapeutic potential, whilst minimising unwanted effects. Here we demonstrate that germline and post-natal targeted knockdown of the PYY preferring receptor (neuropeptide Y (NPY) Y2 receptor (Y2R)) in the afferent vagus nerve is required for the appetite inhibitory effects of physiologically-released PYY, but not peripherally administered pharmacological doses.

What can functional brain imaging teach us about remission of type 2 diabetes?

Aims: With a paradigm shift in attitudes towards type 2 diabetes (T2D), 'weight loss responsive' diabetes is now thought of as a curable disease state. As a result, national programmes are being orchestrated to induce T2D remission soon after diagnosis with aggressive dietary interventions-such as very low-calorie diets (VLCD). However, dietary interventions to achieve weight loss and diabetes remission lack the same long-term sustainability and cardiovascular risk reduction evidence as bariatric surgery.

GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification.

Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on 'around the clock' glucoregulatory processes. Here we show that GWAS meta-analysis of glucose measurements under nonstandardized conditions (random glucose (RG)) in 476,326 individuals of diverse ancestries and without diabetes enables locus discovery and innovative pathophysiological observations. We discovered 120 RG loci represented by 150 distinct signals, including 13 with sex-dimorphic effects, two cross-ancestry and seven rare frequency signals.

Highly specific and non-invasive imaging of Piezo1-dependent activity across scales using GenEPi.

Mechanosensing is a ubiquitous process to translate external mechanical stimuli into biological responses. Piezo1 ion channels are directly gated by mechanical forces and play an essential role in cellular mechanotransduction. However, readouts of Piezo1 activity are mainly examined by invasive or indirect techniques, such as electrophysiological analyses and cytosolic calcium imaging.

Newly detected diabetes during the COVID-19 pandemic: What have we learnt?

The SARS-CoV-2 pandemic has had an unprecedented effect on global health, mortality and healthcare provision. Diabetes has emerged as a key disease entity over the pandemic period, influencing outcomes from COVID-19 but also a tantalising hypothesis that the virus itself may be inducing diabetes. An uptick in diabetes cases over the pandemic has been noted for both type 1 diabetes (in children) and type 2 diabetes but understanding how this increase in incidence relates to the pandemic is challenging.

The Arab COVID-19 Anxiety Syndrome Scale (C-19ASS): COVID-19 anxiety syndrome and psychological symptoms in the Saudi Arabian population.

Introduction: The COVID-19 Anxiety Syndrome Scale (C-19ASS) is a reliable scale assessing dysfunctional coping strategies activated in response to COVID-19 fear and threat. The present study aimed to provide a validation of the Arabic version of the C-19ASS and to explore the association between the C-19ASS and psychological symptoms syndrome.

Method: In Study 1, a community sample of 404 participants completed the Arabic version of the C-19ASS and results were subjected to an exploratory factor analysis.

Divergent acute versus prolonged pharmacological GLP-1R responses in adult β cell-specific β-arrestin 2 knockout mice.

The glucagon-like peptide-1 receptor (GLP-1R) is a major type 2 diabetes therapeutic target. Stimulated GLP-1Rs are rapidly desensitized by β-arrestins, scaffolding proteins that not only terminate G protein interactions but also act as independent signaling mediators. Here, we have assessed in vivo glycemic responses to the pharmacological GLP-1R agonist exendin-4 in adult β cell-specific β-arrestin 2 knockout (KO) mice.

The acute effect of glucagon on components of energy balance and glucose homoeostasis in adults without diabetes: a systematic review and meta-analysis.

Objective: Using a systematic review and meta-analysis, we aimed to estimate the mean effect of acute glucagon administration on components of energy balance and glucose homoeostasis in adults without diabetes.

Methods: CENTRAL, CINAHL, Embase, MEDLINE, PubMed, and Scopus databases were searched from inception to May 2021. To be included, papers had to be a randomised, crossover, single- or double-blind study, measuring ad libitum meal energy intake, energy expenditure, subjective appetite, glucose, and/or insulin following acute administration of glucagon and an appropriate comparator in adults without diabetes.

Diabetes self-management during the COVID-19 pandemic and its associations with COVID-19 anxiety syndrome, depression and health anxiety.

Introduction: The effects of the COVID-19 pandemic on mental health have been profound. Mental health and diabetes self-care are inter-related. We examined whether COVID-19 anxiety, depressive symptoms and health anxiety were associated with domains of diabetes self-management and investigated whether greater COVID-19 anxiety syndrome would independently contribute to suboptimal diabetes self-care.

Why are women still leaving academic medicine? A qualitative study within a London Medical School.

Objectives: To identify factors that influenced women who chose to leave academic medicine.

Design And Main Outcome Measures: Independent consultants led a focus group of women in medicine who had left academia after completion of their postgraduate research degree at Imperial College London Faculty of Medicine. Thematic analysis was performed on the transcribed conversations.

Low-Frequency Oscillations of In Vivo Ambient Extracellular Brain Serotonin.

Serotonin is an important neurotransmitter that plays a major role in many aspects of neuroscience. Fast-scan cyclic voltammetry measures fast in vivo serotonin dynamics using carbon fiber microelectrodes. More recently, fast-scan controlled-adsorption voltammetry (FSCAV) has been developed to measure slower, minute-to-minute changes in ambient extracellular serotonin.

Understanding concepts of generalism and specialism amongst medical students at a research-intensive London medical school.

Background: Many prominent UK medical organisations have identified a need for more generalist clinicians to address the complex requirements of an aging society. We sought to clarify attitudes towards "Specialists" and "Generalists" amongst medical students and junior doctors at Imperial College School of Medicine.

Methods: A survey exploring medical students' beliefs was followed up by qualitative analysis of focus groups of medical students and Imperial-graduate foundation year doctors.

Prevalence, risk factors, and interventions for obesity in Saudi Arabia: A systematic review.

Saudi Arabia (SA) has a reported obesity prevalence greater than the global average. Here, we systematically review firstly the prevalence and associated factors (59 studies) and secondly the pharmacological, lifestyle, and surgical interventions for obesity (body mass index, >30 kg/m ) in SA (29 studies) between December 2020 and March 2021 in PubMed, Medline, Embase, PsycINFO, and Cochrane. Peer-reviewed articles in Arabic and English on human adults (aged >18 years) were searched.

Arginine-vasopressin mediates counter-regulatory glucagon release and is diminished in type 1 diabetes.

Insulin-induced hypoglycemia is a major treatment barrier in type-1 diabetes (T1D). Accordingly, it is important that we understand the mechanisms regulating the circulating levels of glucagon. Varying glucose over the range of concentrations that occur physiologically between the fed and fuel-deprived states (8 to 4 mM) has no significant effect on glucagon secretion in the perfused mouse pancreas or in isolated mouse islets (in vitro), and yet associates with dramatic increases in plasma glucagon.

Intravital imaging of islet Ca dynamics reveals enhanced β cell connectivity after bariatric surgery in mice.

Bariatric surgery improves both insulin sensitivity and secretion and can induce diabetes remission. However, the mechanisms and time courses of these changes, particularly the impact on β cell function, are difficult to monitor directly. In this study, we investigated the effect of Vertical Sleeve Gastrectomy (VSG) on β cell function in vivo by imaging Ca dynamics in islets engrafted into the anterior eye chamber.

Weight Loss by Low-Calorie Diet Versus Gastric Bypass Surgery in People With Diabetes Results in Divergent Brain Activation Patterns: A Functional MRI Study.

Objective: Weight loss achieved with very-low-calorie diets (VLCDs) can produce remission of type 2 diabetes (T2D), but weight regain very often occurs with reintroduction of higher calorie intakes. In contrast, bariatric surgery produces clinically significant and durable weight loss, with diabetes remission that translates into reductions in mortality. We hypothesized that in patients living with obesity and prediabetes/T2D, longitudinal changes in brain activity in response to food cues as measured using functional MRI would explain this difference.

Evaluation of efficacy- versus affinity-driven agonism with biased GLP-1R ligands P5 and exendin-F1.

The glucagon-like peptide-1 receptor (GLP-1R) is an important regulator of glucose homeostasis and has been successfully targeted for the treatment of type 2 diabetes. Recently described biased GLP-1R agonists with selective reductions in β-arrestin versus G protein coupling show improved metabolic actions in vivo. However, two prototypical G protein-favouring GLP-1R agonists, P5 and exendin-F1, are reported to show divergent effects on insulin secretion.

Dysregulation of the Pdx1/Ovol2/Zeb2 axis in dedifferentiated β-cells triggers the induction of genes associated with epithelial-mesenchymal transition in diabetes.

Objective: β-cell dedifferentiation has been revealed as a pathological mechanism underlying pancreatic dysfunction in diabetes. We previously showed that increased miR-7 levels trigger β-cell dedifferentiation and diabetes. We used β-cell-specific miR-7 overexpressing mice (Tg7) to test the hypothesis that loss of β-cell identity triggered by miR-7 overexpression alters islet gene expression and islet microenvironment in diabetes.

Adverse outcomes in COVID-19 and diabetes: a retrospective cohort study from three London teaching hospitals.

Introduction: Patients with diabetes mellitus admitted to hospital with COVID-19 have poorer outcomes. However, the drivers of poorer outcomes are not fully elucidated. We performed detailed characterization of patients with COVID-19 to determine the clinical and biochemical factors that may be drivers of poorer outcomes.