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Within the family of voltage-gated calcium channels (VGCCs), L-type channels (L-VGCCs) represent a well-established therapeutic target for calcium channel blockers, which are widely used to treat hypertension and myocardial ischemia. L-VGCCs outside the cardiovascular system also control key physiological processes such as neuronal plasticity, sensory cell function (e.g. in the inner ear and retin

Oxidative stress has been suggested to contribute to the development of non-alcoholic fatty liver disease (NAFLD). Peroxisome proliferator-activated receptor gamma (PPAR-gamma) heterozygous mice and Pro12Ala (C/G) polymorphism in PPARG exhibited increased resistance to oxidative stress. Smoking increases the production of reactive oxygen species, which could accelerates oxidative stress under over

The pioneer microbiota of the neonate may affect future actions of the immune system. This study aimed to map the pioneer microbiota in healthy neonates vaginally born at term. A subgroup of neonates born large for gestational age (LGA) was compared with the neonates appropriate for gestational age (AGA). Fecal samples were collected, within 48 hours after birth, from 79 neonates. Quantitative pol

Recoverin a member of the neuronal calcium sensor (NCS) branch of the calmodulin superfamily, is expressed in retinal photoreceptor cells and serves as a calcium sensor in vision. Ca2+-induced conformational changes in recoverin cause extrusion of its covalently attached myristate (termed Ca2+-myristoyl switch) that promotes translocation of recoverin to disk membranes during phototransduction in

Context: Postprandial glucose homeostasis is regulated through the secretion of glucagon-like peptide 1 (GLP-1) through stimulation of insulin secretion and inhibition of glucagon secretion. However, how these processes dynamically adapt to demands created by caloric challenges achieved during daily life is not known. Objective: To explore adaptation of incretin and islet hormones after mixed meal

Research conducted over the last 50 years has produced discoveries on the importance of glucose control for reducing the risk of diabetic complications, the pathophysiology of type 2 diabetes, the development and validation of mechanistic glucose-lowering targets, and the preclinical and clinical development of individual drugs. This science established the different drug classes that are clinical

GPRC5B is an orphan receptor belonging to the group C family of G protein-coupled receptors (GPCRs). GPRC5B is abundantly expressed in both human and mouse pancreatic islets, and both GPRC5B mRNA and protein are up-regulated 2.5-fold in islets from organ donors with type 2 diabetes. Expression of Gprc5b is 50% lower in islets isolated from newborn (<3 weeks) than in adult (>36 weeks) mice. Lentivi

Epigenetic variation may contribute to the development of complex metabolic diseases such as type 2 diabetes (T2D). Hepatic insulin resistance is a hallmark of T2D. However, it remains unknown if epigenetic alterations take place in the liver from diabetic subjects. Therefore, we investigated the genome-wide DNA methylation pattern in the liver from subjects with T2D and non-diabetic controls and

OBJECTIVEExamine the efficacy and safety of lixisenatide (20 μg once daily, administered before the morning or evening meal) as add-on therapy in type 2 diabetes patients insufficiently controlled with metformin alone.RESEARCH DESIGN AND METHODSA 24-week, randomized, double-blind, placebo-controlled study in 680 patients with inadequately controlled type 2 diabetes (HbA1c 7-10% [53-86 mmol/mol]).

Glucagon-like peptide-1 (GLP-1) receptor agonists improve islet function and delay gastric emptying in patients with type 2 diabetes mellitus (T2DM). This meta-analysis aimed to investigate the effects of the once-daily prandial GLP-1 receptor agonist lixisenatide on postprandial plasma glucose (PPG), glucagon and insulin levels.

Obese subjects have increased number of enlarged fat cells which are reduced in size but not number in post-obesity. We performed DNA methylation profiling in fat cells with the aim of identifying differentially methylated DNA sites (DMS) linked to adipose hyperplasia (many small fat cells) in post-obesity.

In response to fasting or hyperglycemia, the pancreatic β-cell alters its output of secreted insulin; however the pathways governing this adaptive response are not entirely established. While the precise role of microRNAs (miRNAs) is also unclear, a recurring theme emphasizes their function in cellular stress responses. We recently showed that miR-184, an abundant miRNA in the β-cell, regulates co

The mechanism by which incretins and their effect on insulin secretion increase markedly following gastric bypass surgery (GBP) is not fully elucidated. We hypothesized that a decrease in the activity of dipeptidyl peptidase-4 (DPP-4), the enzyme which inactivates incretins, may explain the rise in incretin levels post-GBP. Fasting plasma DPP-4 activity was measured after 10 kg equivalent weight l

Combining insulin with glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors as glucose-lowering therapy for type 2 diabetes is a promising strategy that has gained considerable interest over the past few years. One advantage of this combination is the complementary mechanistic actions of insulin and GLP-1. Insulin increases glucose utilization and retards

Salt-inducible kinase (SIK) 3 is a virtually unstudied, ubiquitously expressed serine/threonine kinase, belonging to the AMP-activated protein kinase (AMPK)-related family of kinases, all of which are regulated by LKB1 phosphorylation of a threonine residue in their activation (T)-loops. Findings in adrenal cells have revealed a role for cAMP in the regulation of SIK1, and recent findings suggest