A5025390498- Pancreatic function and diabetes
- Diabetes Treatment and Management
- Diabetes Management and Research
- Adrenal Hormones and Disorders
- Estrogen and related hormone effects
- Hormonal Regulation and Hypertension
- Social and Educational Sciences
- RNA Interference and Gene Delivery
- Early Childhood Education and Development
- MicroRNA in disease regulation
- Genetics and Neurodevelopmental Disorders
- Advanced biosensing and bioanalysis techniques
- Diabetes and associated disorders
- Extracellular vesicles in disease
- Calcium signaling and nucleotide metabolism
- Drug Transport and Resistance Mechanisms
- Erythropoietin and Anemia Treatment
- Signaling Pathways in Disease
- Chronic Kidney Disease and Diabetes
- Liver Disease Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- CRISPR and Genetic Engineering
AstraZeneca (Sweden)
2012-2023
Hormone-secreting cells within pancreatic islets of Langerhans play important roles in metabolic homeostasis and disease. However, their transcriptional characterization is still incomplete. Here, we sequenced the transcriptomes thousands human islet from healthy type 2 diabetic donors. We could define specific genetic programs for each individual endocrine exocrine cell type, even rare δ, γ, ε, stellate cells, revealed subpopulations α, β, acinar cells. Intriguingly, δ expressed several...
Receptor-dependent productive uptake of GLP1-conjugated antisense oligonucleotides occurs selectively in pancreatic β-cells.
Abstract Background This post-hoc analysis of the DELIGHT trial assessed effects SGLT2 inhibitor dapagliflozin on iron metabolism and markers inflammation. Methods Patients with type 2 diabetes albuminuria were randomized to dapagliflozin, saxagliptin, or placebo. We measured hemoglobin, (serum iron, transferrin saturation, ferritin), plasma erythropoietin, inflammatory (urinary MCP-1 urinary/serum IL-6) at baseline week 24. Results 360/461 (78.1%) participants had available biosamples....
Interruption of the enterohepatic circulation bile acids increases cholesterol catabolism, thereby stimulating hepatic synthesis from acetate. We hypothesized that such treatment should lower acetate pool which may alter triglyceride and glucose metabolism. explored this using mice deficient ileal sodium-dependent BA transporter (Slc10a2) ob/ob treated with a specific inhibitor Slc10a2. Plasma TG levels were reduced in Slc10a2-deficient mice, when challenged sucrose-rich diet, they displayed...
Significance We reveal that increased expression of Ca V 3.1 channels in rat islets selectively impairs first-phase glucose-stimulated insulin secretion. This deterioration is recapitulated human islets. Its causal role diabetes development clearly manifested an vivo diabetic model. Mechanistically, this due to reduction phosphorylated FoxO1 the cytoplasm, elevated nuclear retention, and decreased syntaxin 1A, SNAP-25, synaptotagmin III a channel- calcineurin-dependent manner. Our findings...
It has been suggested that extracellular vesicles (EVs) can mediate crosstalk between hormones and metabolites within pancreatic tissue. However, the possible effect of EVs on stem cell differentiation into lineages remains unknown. Herein, human islet-derived (h-Islet-EVs) were isolated, characterized subsequently added to induced pluripotent (iPSC) clusters during differentiation. The h-islet-EVs had a mean size 117±7 nm showed positive expression CD63 CD81 EV markers as measured by ELISA....
Aims/Hypothesis GPR44 (DP2, PTGDR2, CRTh2) is the receptor for pro-inflammatory mediator prostaglandin D2 (PGD2) and it enriched in human islets. In rodent islets, PGD2 produced response to glucose, suggesting that PGD2-GPR44/DP2 axis may play a role islet function during hyperglycemia. Consequently, aim of this work was elucidate insulinotropic antagonism vitro beta-cells type 2 diabetes (T2DM) patients. Methods We determined drive on secretion by glucose IL-1beta, as well as, impact...
<h3>Background:</h3> AZD9567 is a novel oral selective glucocorticoid receptor modulator (SGRM) developed to have an improved safety profile versus prednisolone while maintaining efficacy. <h3>Objectives:</h3> To show clinical evidence of differentiation for compared with respect glucose homeostasis and investigate the underlying effects on metabolism in human cell systems <i>in vitro</i>. <h3>Methods:</h3> In dose escalation study (NCT02760316), healthy volunteers were randomized 5-day...
Insufficient pancreatic β-cell mass or function is one of the main causes underlying diabetes mellitus. Glycogen synthase kinase 3 (GSK3) a ubiquitously expressed serine/threonine kinase. GSK3 encoded by two known genes, alpha (GSK3A) and beta (GSK3B), small molecule inhibitors targeting both are to induce micronucleation. Isoform specific GSK3B have demonstrated increased cell proliferation expansion islets in human rodents. However, many target dual specificity...