Nicotinic Signaling Stimulates Glucagon Secretion in Mouse and Human Pancreatic α-Cells.

Smoking is widely regarded as a risk factor for type 2 diabetes because nicotine contributes to insulin resistance by desensitizing the insulin receptors in muscle, liver, or fat. Little is known, however, about the immediate regulation of islet hormonal output by nicotine, an agonist of ionotropic cholinergic receptors. We investigated this by imaging cytosolic Ca2+ dynamics in mouse and human islets using confocal microscopy and measuring glucagon secretion in response to the alkaloid from isolated mouse islets.

Loss of electrical β-cell to δ-cell coupling underlies impaired hypoglycaemia-induced glucagon secretion in type-1 diabetes.

Diabetes mellitus involves both insufficient insulin secretion and dysregulation of glucagon secretion. In healthy people, a fall in plasma glucose stimulates glucagon release and thereby increases counter-regulatory hepatic glucose production. This response is absent in many patients with type-1 diabetes (T1D), which predisposes to severe hypoglycaemia that may be fatal and accounts for up to 10% of the mortality in patients with T1D.

Cafeteria diet compromises natural adaptations of islet cell transdifferentiation and turnover in pregnancy.

Background: Pancreatic islet β-cell mass expands during pregnancy, but underlying mechanisms are not fully understood. This study examines the impact of pregnancy and cafeteria diet on islet morphology, associated cellular proliferation/apoptosis rates as well as β-cell lineage.

Methods: Non-pregnant and pregnant Ins1;Rosa26-eYFP transgenic mice were maintained on either normal or high-fat cafeteria diet, with pancreatic tissue obtained at 18 days gestation.

[P]PP, a stable, long-acting pancreatic polypeptide analogue, evokes weight lowering and pancreatic beta-cell-protective effects in obesity-associated diabetes.

Aim: To thoroughly investigate the impact of sustained neuropeptide Y4 receptor (NPY4R) activation in obesity-associated diabetes.

Methods: Initially, the prolonged pharmacodynamic profile of the enzymatically stable pancreatic polypeptide (PP) analogue, [P]PP, was confirmed in normal mice up to 24 h after injection. Subsequent to this, [P]PP was administered twice daily (25 nmol/kg) for 28 days to high-fat-fed mice with streptozotocin-induced insulin deficiency, known as HFF/STZ mice.

The impact of GLP-1 signalling on the energy metabolism of pancreatic islet β-cells and extrapancreatic tissues.

Glucagon-like peptide-1 signalling impacts glucose homeostasis and appetite thereby indirectly affecting substrate availability at the whole-body level. The incretin canonically produces an insulinotropic effect, thereby lowering blood glucose levels by promoting the uptake and inhibiting the production of the sugar by peripheral tissues. Likewise, GLP-1 signalling within the central nervous system reduces the appetite and food intake, whereas its gastric effect delays the absorption of nutrients, thus improving glycaemic control and reducing the risk of postprandial hyperglycaemia.

Dopamine signalling in pancreatic islet cells and role in adaptations to metabolic stress.

Objectives: Dopamine and related receptors are evidenced in pancreatic endocrine tissue, but the impact on islet β-cell stimulus-secretion as well as (patho)physiological role are unclear.

Methods: The present study has evaluated islet cell signalling pathways and biological effects of dopamine, as well as alterations of islet dopamine in rodent models of diabetes of different aetiology.

Key Findings: The dopamine precursor l-DOPA partially impaired glucose tolerance in mice and attenuated glucose-, exendin-4, and alanine-induced insulin secretion.

The endoplasmic reticulum plays a key role in α-cell intracellular Ca dynamics and glucose-regulated glucagon secretion in mouse islets.

Glucagon is secreted by pancreatic α-cells to counteract hypoglycaemia. How glucose regulates glucagon secretion remains unclear. Here, using mouse islets, we studied the role of transmembrane and endoplasmic reticulum (ER) Ca on intrinsic α-cell glucagon secretion.

Molecular determinants and intracellular targets of taurine signalling in pancreatic islet β-cells.

Aim: Despite its abundance in pancreatic islets of Langerhans and proven antihyperglycemic effects, the impact of the essential amino acid, taurine, on islet β-cell biology has not yet received due consideration, which prompted the current studies exploring the molecular selectivity of taurine import into β-cells and its acute and chronic intracellular interactions.

Methods: The molecular aspects of taurine transport were probed by exposing the clonal pancreatic BRIN BD11 β-cells and primary mouse and human islets to a range of the homologs of the amino acid (assayed at 2-20 mM), using the hormone release and imaging of intracellular signals as surrogate read-outs. Known secretagogues were employed to profile the interaction of taurine with acute and chronic intracellular signals.

GLP-1 metabolite GLP-1(9-36) is a systemic inhibitor of mouse and human pancreatic islet glucagon secretion.

Aims/hypothesis: Diabetes mellitus is associated with impaired insulin secretion, often aggravated by oversecretion of glucagon. Therapeutic interventions should ideally correct both defects. Glucagon-like peptide 1 (GLP-1) has this capability but exactly how it exerts its glucagonostatic effect remains obscure.

Pancreatic islet cell plasticity: Pathogenic or therapeutically exploitable?

The development of pancreatic islet endocrine cells is a tightly regulated process leading to the generation of distinct cell types harbouring different hormones in response to small changes in environmental stimuli. Cell differentiation is driven by transcription factors that are also critical for the maintenance of the mature islet cell phenotype. Alteration of the insulin-secreting β-cell transcription factor set by prolonged metabolic stress, associated with the pathogenesis of diabetes, obesity or pregnancy, results in the loss of β-cell identity through de- or transdifferentiation.

Anxiety, Stress Perception, and Coping Strategies among Students with COVID-19 Exposure.

: Studying anxiety, stress, and coping strategies during the COVID-19 pandemic is crucial to mitigate the negative effects associated with infection risk and disease consequences. : This study aimed to investigate anxiety levels, stress perception, and coping strategies in relation to the presence of illness. : A cross-sectional online survey was conducted anonymously among 3950 university students from Poland (1822), Lithuania (232), and the Russian exclave of Kaliningrad (1896).

Embedding Scientific Communication and Digital Capabilities in the Undergraduate Biomedical Science Curriculum.

Scientific communication, particularly the dissemination of research findings to both the scientific community and the general public, are skills required of graduates embarking on post-graduate studies and employment within the biomedical sciences sector. The aims of this action research project were to i) co-design an online scientific communication and digital capabilities resource, constructively aligned to the learning objectives of a final year undergraduate investigative research project; ii) ensure resource flexibility for future adaptation by others iii) embed authentic scientific communication learning assessments, namely, the preparation of a lay summary and visual abstract and iv) promote students' awareness of developed digital capabilities and transferable skills through written reflection. Student engagement, self-efficacy, experiences and performance and staff perceptions ( = 15) were evaluated by a mixed methods approach.

Taurine rescues pancreatic β-cell stress by stimulating α-cell transdifferentiation.

The semi-essential ubiquitous amino acid taurine has been shown to alleviate obesity and hyperglycemia in humans; however, the pathways underlying the antidiabetic actions have not been characterized. We explored the effect of chronic taurine exposure on cell biology of pancreatic islets, in degenerative type 1-like diabetes. The latter was modeled by small dose of streptozotocin (STZ) injection for 5 days in mice, followed by a 10-day administration of taurine (2% w/v, orally) in the drinking water.

NKCC transport mediates the insulinotropic effects of taurine and other small neutral amino acids.

Aims: Despite its high concentration in pancreatic islets of Langerhans and broad range of antihyperglycemic effects, the route facilitating the import of dietary taurine into pancreatic β-cell and mechanisms underlying its insulinotropic activity are unclear. We therefore studied the impact of taurine on beta-cell function, alongside that of other small neutral amino acids, L-alanine and L-proline.

Main Methods: Pharmacological profiling of insulin secretion was conducted using clonal BRIN BD11 β-cells, the impact of taurine on the metabolic fate of glucose carbons was assessed using NMR and the findings were verified by real-time imaging of Ca dynamics in the cytosol of primary mouse and human islet beta-cells.

Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells.

Chronic hyperglycaemia causes a dramatic decrease in mitochondrial metabolism and insulin content in pancreatic β-cells. This underlies the progressive decline in β-cell function in diabetes. However, the molecular mechanisms by which hyperglycaemia produces these effects remain unresolved.

Effects of artemether on pancreatic islet morphology, islet cell turnover and α-cell transdifferentiation in insulin-deficient GluCreERT2;ROSA26-eYFP diabetic mice.

Objectives: The antimalarial drug artemether is suggested to effect pancreatic islet cell transdifferentiation, presumably through activation γ-aminobutyric acid receptors, but this biological action is contested.

Methods: We have investigated changes in α-cell lineage in response to 10-days treatment with artemether (100 mg/kg oral, once daily) on a background of β-cell stress induced by multiple low-dose streptozotocin (STZ) injection in GluCreERT2; ROSA26-eYFP transgenic mice.

Key Findings: Artemether intervention did not affect the actions of STZ on body weight, food and fluid intake or blood glucose.

Stress Perception and Coping Strategies of Students on Both Sides of the EU's Eastern Border during the COVID-19 Pandemic.

The aim of the study was to compare the perception of stress and the characteristic coping-strategies among students in the context of the different anti-pandemic measures taken in Belarus, Poland, and the Russian exclave of Kaliningrad. A cross-sectional online survey using standardized questionnaires (Perceived Stress Scale-PSS-10 and Brief-COPE-Mini-COPE inventory) was conducted among 3113 students of seven universities in three neighboring regions on both sides of the eastern border of the EU. The groups that are the most prone to stress are the Polish and Russians students.

Monitoring glycolytic dynamics in single cells using a fluorescent biosensor for fructose 1,6-bisphosphate.

Cellular metabolism is regulated over space and time to ensure that energy production is efficiently matched with consumption. Fluorescent biosensors are useful tools for studying metabolism as they enable real-time detection of metabolite abundance with single-cell resolution. For monitoring glycolysis, the intermediate fructose 1,6-bisphosphate (FBP) is a particularly informative signal as its concentration is strongly correlated with flux through the whole pathway.

Liver glycogen phosphorylase is upregulated in glioblastoma and provides a metabolic vulnerability to high dose radiation.

Channelling of glucose via glycogen, known as the glycogen shunt, may play an important role in the metabolism of brain tumours, especially in hypoxic conditions. We aimed to dissect the role of glycogen degradation in glioblastoma (GBM) response to ionising radiation (IR). Knockdown of the glycogen phosphorylase liver isoform (PYGL), but not the brain isoform (PYGB), decreased clonogenic growth and survival of GBM cell lines and sensitised them to IR doses of 10-12 Gy.

Phytotherapeutic Approaches to the Prevention of Age-Related Changes and the Extension of Active Longevity.

Maintaining quality of life with an increase in life expectancy is considered one of the global problems of our time. This review explores the possibility of using natural plant compounds with antioxidant, anti-inflammatory, anti-glycation, and anti-neurodegenerative properties to slow down the onset of age-related changes. Age-related changes such as a decrease in mental abilities, the development of inflammatory processes, and increased risk of developing type 2 diabetes have a significant impact on maintaining quality of life.

GABA and insulin but not nicotinamide augment α- to β-cell transdifferentiation in insulin-deficient diabetic mice.

Aim: Poorly controlled diabetes is characterised by a partial or complete loss of pancreatic islet β-cells, which deprives the remaining islet cells of important β-cell-derived soluble signals, such as insulin or GABA. We aimed to dissect the role of the two signals in the development of islet α-cells, focusing specifically on α-/β-cell transdifferentiation and using the stem cell differentiation factor nicotinamide as a comparator.

Methods: Streptozotocin (STZ)-treated diabetic mice expressing a fluorescent reporter in pancreatic islet α-cells were injected with GABA (10 mg/kg once daily), nicotinamide (150 mg/kg once daily) or insulin (1U/kg three times daily) for 10 days.

Classical and non-classical islet peptides in the control of β-cell function.

The dual role of the pancreas as both an endocrine and exocrine gland is vital for food digestion and control of nutrient metabolism. The exocrine pancreas secretes enzymes into the small intestine aiding digestion of sugars and fats, whereas the endocrine pancreas secretes a cocktail of hormones into the blood, which is responsible for blood glucose control and regulation of carbohydrate, protein and fat metabolism. Classical islet hormones, insulin, glucagon, pancreatic polypeptide and somatostatin, interact in an autocrine and paracrine manner, to fine-tube the islet function and insulin secretion to the needs of the body.

Imaging Meets Cytometry: Analyzing Heterogeneous Functional Microscopic Data from Living Cell Populations.

Biological tissue consists of populations of cells exhibiting different responses to pharmacological stimuli. To probe the heterogeneity of cell function, we propose a multiplexed approach based on real-time imaging of the secondary messenger levels within each cell of the tissue, followed by extraction of the changes of single-cell fluorescence over time. By utilizing a piecewise baseline correction, we were able to quantify the effects of multiple pharmacological stimuli added and removed sequentially to pancreatic islets of Langerhans, thereby performing a deep functional profiling for each cell within the islet.

The Role of Plant-Based Protein Functional Food in Preventing Acute Respiratory Disease: A Case Study.

The Kaliningrad region is known for its specific climate, which can negatively affect the adaptive potential of the body. This manifests in an increased incidence of respiratory diseases and skin conditions. To prevent high morbidity, a plant protein product was included in the diet of first-year university students.