Salivary proteomics and metaproteomics identifies distinct molecular and taxonomic signatures of type-2 diabetes.

Background: Saliva is a protein-rich body fluid for noninvasive discovery of biomolecules, containing both human and microbial components, associated with various chronic diseases. Type-2 diabetes (T2D) imposes a significant health and socio-economic burden. Prior research on T2D salivary microbiome utilized methods such as metagenomics, metatranscriptomics, 16S rRNA sequencing, and low-throughput proteomics.

Glucagon-like peptide-1 increases heart rate by a direct action on the sinus node.

Aims: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used to treat type 2 diabetes and obesity. Albeit cardiovascular outcomes generally improve, treatment with GLP-1 RAs is associated with increased heart rate, the mechanism of which is unclear.

Methods And Results: We employed a large animal model, the female landrace pig, and used multiple in vivo and ex vivo approaches including pharmacological challenges, electrophysiology, and high-resolution mass spectrometry to explore how GLP-1 elicits an increase in heart rate.

The renal vasodilatation from β-adrenergic activation in vivo in rats is not driven by K7 and BK channels.

The mechanisms behind renal vasodilatation elicited by stimulation of β-adrenergic receptors are not clarified. As several classes of K channels are potentially activated, we tested the hypothesis that KV7 and BKCa channels contribute to the decreased renal vascular tone in vivo and in vitro. Changes in renal blood flow (RBF) during β-adrenergic stimulation were measured in anaesthetized rats using an ultrasonic flow probe.

A randomized, double-blind, crossover study of the effect of the fluoroquinolone moxifloxacin on glucose levels and insulin sensitivity in young men and women.

Aim: The voltage-gated potassium channel K 11.1 is important for repolarizing the membrane potential in excitable cells such as myocytes, pancreatic α- and β-cells. Moxifloxacin blocks the K 11.

Necropsy Validation of a Novel Method for Left Ventricular Mass Quantification in Porcine Transthoracic and Transdiaphragmal Echocardiography.

Introduction: Increased left ventricular mass (LVM) is one of the most powerful predictors of adverse cardiovascular events. Clinical evaluation requires reliable, accurate and reproducible echocardiographic LVM-quantification to manage patients. For this purpose, we have developed a novel two-dimensional (2D) method based on adding the mean wall thickness to the left ventricular volume acquired by the biplane method of disks, which has recently been validated in humans using cardiac magnetic resonance as reference value.

Celebrities in the heart, strangers in the pancreatic beta cell: Voltage-gated potassium channels K 7.1 and K 11.1 bridge long QT syndrome with hyperinsulinaemia as well as type 2 diabetes.

Voltage-gated potassium (K ) channels play an important role in the repolarization of a variety of excitable tissues, including in the cardiomyocyte and the pancreatic beta cell. Recently, individuals carrying loss-of-function (LoF) mutations in KCNQ1, encoding K 7.1, and KCNH2 (hERG), encoding K 11.

Age-dependent transition from islet insulin hypersecretion to hyposecretion in mice with the long QT-syndrome loss-of-function mutation Kcnq1-A340V.

Loss-of-function (LoF) mutations in KCNQ1, encoding the voltage-gated K channel K7.1, lead to long QT syndrome 1 (LQT1). LQT1 patients also present with post-prandial hyperinsulinemia and hypoglycaemia.

Inhibition of Adenosine Pathway Alters Atrial Electrophysiology and Prevents Atrial Fibrillation.

Background: Adenosine leads to atrial action potential (AP) shortening through activation of adenosine 1 receptors (A-R) and subsequent opening of G-protein-coupled inwardly rectifying K channels. Extracellular production of adenosine is drastically increased during stress and ischemia.

Objective: The aim of this study was to address whether the pharmacological blockade of endogenous production of adenosine and of its signaling prevents atrial fibrillation (AF).

Aberrant sinus node firing during β-adrenergic stimulation leads to cardiac arrhythmias in diabetic mice.

Aim: Cardiovascular complications, including cardiac arrhythmias, result in high morbidity and mortality in patients with type-2 diabetes mellitus (T2DM). Clinical and experimental data suggest electrophysiological impairment of the natural pacemaker of the diabetic heart. The present study examined sinoatrial node (SAN) arrhythmias in a mouse model of T2DM and physiologically probed their underlying cause.

Comparison of hemodynamics, cardiac electrophysiology, and ventricular arrhythmia in an open- and a closed-chest porcine model of acute myocardial infarction.

Ventricular fibrillation (VF) during acute myocardial infarction (AMI) is an important contributor to sudden cardiac death. Large animal models are widely used to study AMI-induced arrhythmia, but the mode of AMI induction ranges from thoracotomy and surgical ligation of a coronary vessel (open chest) to minimally invasive techniques, including balloon occlusion (closed chest). How the choice of induction affects arrhythmia development is unclear.

Ventricular Arrhythmias in First Acute Myocardial Infarction: Epidemiology, Mechanisms, and Interventions in Large Animal Models.

Ventricular arrhythmia and subsequent sudden cardiac death (SCD) due to acute myocardial infarction (AMI) is one of the most frequent causes of death in humans. Lethal ventricular arrhythmias like ventricular fibrillation (VF) prior to hospitalization have been reported to occur in more than 10% of all AMI cases and survival in these patients is poor. Identification of risk factors and mechanisms for VF following AMI as well as implementing new risk stratification models and therapeutic approaches is therefore an important step to reduce mortality in people with high cardiovascular risk.

Arrhythmia development during inhibition of small-conductance calcium-activated potassium channels in acute myocardial infarction in a porcine model.

Aims: Acute myocardial infarction (AMI) is associated with intracellular Ca2+ build-up. In healthy ventricles, small conductance Ca2+-activated K+ (SK) channels are present but do not participate in repolarization. However, SK current is increased in chronic myocardial infarction and heart failure, and recently, SK channel inhibition was demonstrated to reduce arrhythmias in AMI rats.

Low-Dose Adrenaline Reduces Blood Pressure Acutely in Anesthetized Pigs Through a β2-Adrenergic Pathway.

Adrenaline (epinephrine) is one of the prime messengers of the fight-or-flight response, favoring the activation of β-adrenergic receptors. Although general vasoconstriction to nonessential tissues is imperative, the vasodilatory effect of β-adrenergic receptor activation contends with this. We aimed to determine the dose-dependent effects of adrenaline on hemodynamics and to test whether adrenaline could lower blood pressure (BP) through a β2-adrenergic pathway.

Amiodarone Treatment in the Early Phase of Acute Myocardial Infarction Protects Against Ventricular Fibrillation in a Porcine Model.

Ventricular fibrillation (VF) occurring in the first minutes to hours of acute myocardial infarction (AMI) is a frequent cause of death and treatment options are limited. The aim was to test whether early infusion of amiodarone 10 min after onset of AMI reduced the incidence of VF in a porcine model. Eighteen female Danish landrace pigs were randomized to a control and an amiodarone group.

Patients With Long-QT Syndrome Caused by Impaired -Encoded K11.1 Potassium Channel Have Exaggerated Endocrine Pancreatic and Incretin Function Associated With Reactive Hypoglycemia.

Background: Loss-of-function mutations in (encoding the K11.1 voltage-gated potassium channel) cause long-QT syndrome type 2 (LQT2) because of prolonged cardiac repolarization. However, K11.