Spatiotemporal profiling of adhesion G protein-coupled receptors in developing mouse and human pancreas reveals a role for GPR56 in islet development.

Introduction: G protein-coupled receptors (GPCRs) are cell-surface proteins that are targeted therapeutically for a range of disorders, including diabetes. Adhesion GPCRs (aGPCRs) are the second largest class of the GPCR superfamily and some members of this family have been implicated in appropriate organ development. However, the role of aGPCRs in endocrine pancreas specification is not yet known.

Identification of Potential Plant-Derived Pancreatic Beta-Cell-Directed Agents Using New Custom-Designed Screening Method: as an Example.

Background: Folk medicines are attractive therapeutic agents for treating type 2 diabetes mellitus (T2DM). Most plant extracts that have been suggested to restore β-cells function were tested in vivo. Some only have been tested in vitro to determine whether they have a direct effect on β-cells islets of Langerhans.

Mouse islet-derived stellate cells are similar to, but distinct from, mesenchymal stromal cells and influence the beta cell function.

Aims: Evidence is accumulating of the therapeutic benefits of mesenchymal stromal cells (MSCs) in diabetes-related conditions. We have identified a novel population of stromal cells within islets of Langerhans - islet stellate cells (ISCs) - which have a similar morphology to MSCs. In this study we characterize mouse ISCs and compare their morphology and function to MSCs to determine whether ISCs may also have therapeutic potential in diabetes.

Kisspeptin upregulates β-cell serotonin production during pregnancy.

During pregnancy the maternal pancreatic islets of Langerhans undergo adaptive changes to compensate for gestational insulin resistance. The lactogenic hormones are well established to play a key role in regulating the islet adaptation to pregnancy, and one of the mechanisms through which they act is through upregulating β-cell serotonin production. During pregnancy islet serotonin levels are significantly elevated, where it is released from the β-cells to drive the adaptive response through paracrine and autocrine effects.

Mesenchymal stromal cell secretory molecules improve the functional survival of human islets.

Aims: Human islet transplantation as a therapy for type 1 diabetes is compromised by the loss of functional beta cells in the immediate post-transplantation period. Mesenchymal stromal cells (MSCs) and MSC-derived secretory peptides improve the outcomes of islet transplantation in rodent models of diabetes. Here, we utilized a mouse model for human islet transplantation and assessed the effects of a cocktail of MSC-secreted peptides (screened by MSC-secretome for human islet GPCRs) on the functional survival of human islets.

Phage-Like Microvirus Genome Sequence Identified in Wastewater in Arizona, USA, in November 2020 Encodes an Endolysin and a Putative Multiheme Cytochrome -like Protein.

We describe the genome (4,696 nucleotides [GC content, 56%; coverage, 3,641×) of MAZ-Nov-2020, a microvirus identified from municipal wastewater in Maricopa County, Arizona, USA, in November 2020. The MAZ-Nov-2020 genome encodes major capsid protein, endolysin, replication initiator protein, and two hypothetical proteins, one of which was predicted to likely be a membrane-associated multiheme cytochrome .

The Switch and Reciprocating Models for the Function of ABC Multidrug Exporters: Perspectives on Recent Research.

ATP-binding cassette (ABC) transporters comprise a large superfamily of primary active transporters, which are integral membrane proteins that couple energy to the uphill vectorial transport of substrates across cellular membranes, with concomitant hydrolysis of ATP. ABC transporters are found in all living organisms, coordinating mostly import in prokaryotes and export in eukaryotes. Unlike the highly conserved nucleotide binding domains (NBDs), sequence conservation in the transmembrane domains (TMDs) is low, with their divergent nature likely reflecting a need to accommodate a wide range of substrate types in terms of mass and polarity.

Commiphora myrrha stimulates insulin secretion from β-cells through activation of atypical protein kinase C and mitogen-activated protein kinase.

Ethnopharmacological Relevance: Ayurvedic medicine has been used in the treatment of diabetes mellitus for centuries. In Arabia and some areas of Africa, Commiphora myrrha (CM) has been extensively used as a plant-based remedy. We have previously shown that an aqueous CM resin solution directly stimulates insulin secretion from MIN6 cells, a mouse β-cell line, and isolated mouse and human islets.

Caring for the injured: Exploring the immediate and long-term consequences of injury in medieval Cambridge, England.

Objective: To combine paleopathological and biomechanical analysis to reconstruct the impact that a severe skeletal injury had on an individual's ability to function and participate in medieval society.

Materials: Three medieval individuals from Cambridge, England with ante-mortem fractures to the lower limb were analyzed.

Methods: Plain X-rays were used to determine the degree of malunion, rotation and overlap of each fracture.

In vitro evaluation of the interaction of the cannabis constituents cannabichromene and cannabichromenic acid with ABCG2 and ABCB1 transporters.

Cannabichromene (CBC) and cannabichromenic acid (CBCA) are cannabis constituents currently under evaluation for their therapeutic potential, but their pharmacological properties have not been thoroughly investigated. The most studied ATP-binding cassette (ABC) transporters, ABC subfamily G member 2 (ABCG2) and ABC subfamily B member 1 (ABCB1) limit absorption of substrate drugs in the gut and brain. Moreover, inhibitors of these proteins can lead to clinically significant drug-drug interactions (DDIs).

Theory protection: Do humans protect existing associative links?

Theories of associative learning often propose that learning is proportional to prediction error, or the difference between expected events and those that occur. Spicer et al. (2020) suggested an alternative, that humans might instead selectively attribute surprising outcomes to cues that they are not confident about, to maintain cue-outcome associations about which they are more confident.

Excitotoxic lesions of the perirhinal cortex leave intact rats' gustatory sensory preconditioning.

We report findings from two sensory preconditioning experiments in which rats consumed two flavoured solutions, each with two gustatory components (AX and BY), composed of sweet, bitter, salt, and acid elements. After this pre-exposure, rats were conditioned to X by pairing with lithium chloride. Standard sensory preconditioning was observed: Consumption of flavour A was less than that of B.

Similarities and differences: Comment on Chan et al. (2021).

Spicer et al. (2020) reported a series of causal learning experiments in which participants appeared to learn most readily about cues when they were not certain of their causal status and proposed that their results were a consequence of participants' use of theory protection. In the present issue, Chan et al.

SNAP-tag-enabled super-resolution imaging reveals constitutive and agonist-dependent trafficking of GPR56 in pancreatic β-cells.

Objective: Members of the adhesion G protein-coupled receptor (aGPCR) subfamily are important actors in metabolic processes, with GPR56 (ADGRG1) emerging as a possible target for type 2 diabetes therapy. GPR56 can be activated by collagen III, its endogenous ligand, and by a synthetic seven amino-acid peptide (TYFAVLM; P7) contained within the GPR56 Stachel sequence. However, the mechanisms regulating GPR56 trafficking dynamics and agonist activities are not yet clear.

Gout and 'Podagra' in medieval Cambridge, England.

Objective: To estimate the prevalence rate of gout and to explore the social factors that contributed to its development in the various sub-populations in medieval Cambridge.

Materials: 177 adult individuals from four medieval cemeteries located in and around Cambridge, UK.

Methods: Lesions were assessed macroscopically and radiographically.

Protecting islet functional viability using mesenchymal stromal cells.

Islet transplantation is an emerging treatment for type 1 diabetes which offers the prospect of physiological control of blood glucose and reductions in acute hypoglycaemic episodes. However, current protocols are limited by a rapid decline in islet functional viability during the isolation process, culture period, and post-transplantation. Much of this can be attributed to the deleterious effects of hypoxic and cytokine stressors on β cells.

The KINGS Mouse: A Novel Model of β-Cell Endoplasmic Reticulum Stress and Human Diabetes.

Animal models are important tools in diabetes research because ethical and logistical constraints limit access to human tissue. β-Cell dysfunction is a common contributor to the pathogenesis of most types of diabetes. Spontaneous hyperglycemia was developed in a colony of C57BL/6J mice at King's College London (KCL).

Is the emperor wearing shorts? The published structures of ABC transporters.

ABC transporters use the energy of ATP binding and hydrolysis to transport substrates across cellular membranes. They comprise two highly conserved nucleotide binding domains and two transmembrane domains that form the transmembrane channel and contain the substrate binding sites. Structural analyses have found a variety of seemingly unrelated folds for the ABC transporter transmembrane domains, and from these, a set of diverse mechanistic models has been inferred.

Pancreatic Fat is not significantly correlated with β-cell Dysfunction in Patients with new-onset Type 2 Diabetes Mellitus using quantitative Computed Tomography.

Type 2 diabetes mellitus (T2DM) is a chronic condition resulting from insulin resistance and insufficient β-cell secretion, leading to improper glycaemic regulation. Previous studies have found that excessive fat deposits in organs such as the liver and muscle can cause insulin resistance through lipotoxicity that affects β-cell function. The relationships between fat deposits in pancreatic tissue, the function of β-cells, the method of visceral fat evaluation and T2DM have been sought by researchers.

Islet Stellate Cells Regulate Insulin Secretion via Wnt5a in Min6 Cells.

Background: Type 2 diabetes mellitus is a serious public health problem worldwide. Accumulating evidence has shown that -cell dysfunction is an important mechanism underlying diabetes mellitus. The changes in the physiological state of islet stellate cells (ISCs) and the effects of these cells on -cell dysfunction is an important mechanism underlying diabetes mellitus.

Vitamin A deficiency causes islet dysfunction by inducing islet stellate cell activation via cellular retinol binding protein 1.

Vitamin A (VA) plays an essential role in pancreatic homeostasis. Islet stellate cells (ISCs) are VA-storing cells in pancreatic islets. Herein, we have investigated the effect of VA on glucose homeostasis trough regulation of ISCs function in dietary VA deficiency model mice.

UCN2: a new candidate influencing pancreatic β-cell adaptations in pregnancy.

The corticotropin-releasing hormone (CRH) family of peptides, including urocortin (UCN) 1, 2 and 3, are established hypothalamic neuroendocrine peptides, regulating the physiological and behaviour responses to stress indirectly, via the hypothalamic-pituitary-adrenal (HPA) axis. More recently, these peptides have been implicated in diverse roles in peripheral organs through direct signalling, including in placental and pancreatic islet physiology. CRH has been shown to stimulate insulin release through activation of its cognate receptors, CRH receptor 1 (CRHR1) and 2.

Optimizing beta cell function through mesenchymal stromal cell-mediated mitochondria transfer.

Pretransplant islet culture is associated with the loss of islet cell mass and insulin secretory function. Insulin secretion from islet β-cells is primarily controlled by mitochondrial ATP generation in response to elevations in extracellular glucose. Coculture of islets with mesenchymal stromal cells (MSCs) improves islet insulin secretory function in vitro, which correlates with superior islet graft function in vivo.