Pancreatic function and diabetes

This study shows sildenafil enhances insulin secretion in pancreatic β cells by increasing calcium influx, independent of L-type Ca2+ channels and PDE5.

The paper examines islet and acinar cell secretion in different pancreatic regions across diabetes stages, finding reduced insulin secretion and beta-cell volume in T1D with normal enzyme secretion.

This study shows that clonal human beta-cell spheroids enhance electrical activity and hormone secretion compared to monolayers, suggesting they are better models for studying beta-cell function.

This study shows that RFX6 haploinsufficiency impairs beta cell function, leading to reduced insulin secretion and increased diabetes risk.

This paper generates pancreatic aggregates from mouse stem cells with mesoderm and pancreatic progenitors, showing increased endocrine cell production compared to controls.

This study shows that IDE deficiency in mice causes a low-level UPR, enhances beta cell proliferation, and protects against autoimmune diabetes through an anti-inflammatory pathway.

The paper identifies multiple genetic variants at the SLC30A8 locus that influence enhancer activity and β cell function, with some variants affecting gene expression and insulin secretion.

The paper shows that adipocyte PI3K signaling controls basal insulin secretion via the adipoincretin effect, independent of glucose levels.

The paper uses 3D imaging to reveal new heterogeneity in human pancreatic islets, showing 50% lack glucagon-producing cells.

The paper characterizes mechanisms of human glucokinase variants by analyzing their abundance and stability, identifying residues that affect metabolic stability and conformational dynamics.

The paper identifies chromosome 20p11.2 deletions as a cause of congenital hyperinsulinism by disrupting FOXA2 expression in pancreatic beta-cells.

This study shows that serum from pregnant donors can stimulate human beta cell proliferation and insulin secretion, suggesting potential for beta cell expansion.

This study shows proinflammatory cytokines suppress NMD activity in β-cells by downregulating UPF3B, leading to increased alternative splicing and ECM-related gene expression, which contributes to β-cell dysfunction.

This study differentiates Wharton's Jelly-derived mesenchymal stem cells into insulin-producing cells using a 3D scaffold, showing improved functionality compared to 2D cultures.

This study compares SC-β cells with fetal and adult β cells using single-cell sequencing, finding they share a core β-cell identity but have unique transcriptional profiles with neural-biased gene networks.

This study investigates two INS mutations causing permanent neonatal diabetes, showing they impair beta cell function through misfolded proinsulin, ER stress, and dedifferentiation.

This study shows IAPP-GFP localizes to mitochondria and forms filamentous aggregates in C. elegans, suggesting potential as a tool for screening IAPP-solubilizing compounds for T2D therapy.

The paper monitors miR-15a and miR-124 expression during adipose-derived mesenchymal stem cell differentiation into pancreatic beta-cells over 28 days, finding increased expression at day 28.

This paper uses a mechanistic model to evaluate how glucagon contributes to glucose regulation and how insulin dysfunction affects glucagon response in diabetes.

The paper validates a new ISS model for estimating insulin sensitivity and beta-cell function from OGTTs, showing strong correlation with gold-standard methods across diverse populations.

This study shows that sustained high glucose reduces translation of mRNAs involved in insulin secretion in beta-cells, impairing their function.

The paper identifies homozygous loss of function variants in ZNF808 as a cause of pancreatic agenesis in humans, showing its role in repressing transposable elements during pancreatic development.

This study shows that Robo2 in adult beta cells actively maintains islet architecture, as its deletion leads to loss of architecture without affecting beta cell identity or function.

This study develops a kinetic model of β-cell metabolism to identify key regulatory points in pyruvate cycling pathways involved in insulin secretion and NADPH production.

This paper develops a practical and robust method to assess primary pancreatic islet metabolic fluxes using standard Seahorse equipment, showing reliable respiration and functional responses in mouse and rat islets.

This study functionally interrogates 20 T2D-associated genes using isogenic hESC-derived β-like cells, identifying variants and genes linked to insulin production and lipotoxicity sensitivity.

The paper shows that disrupting actin filaments increases glucose-stimulated insulin secretion without affecting the cortical actin cytoskeleton.

This study shows that the leptin receptor in mouse delta cells does not affect beta-cell function or glucose homeostasis.

This study shows that the KCNK16 L114P mutation causes neonatal diabetes and glucose dyshomeostasis in adult mice by disrupting islet insulin secretion and increasing glucagon secretion.

This study identifies signaling pathways that enable the unlimited expansion of human pancreatic progenitors in defined conditions, leading to efficient and reproducible cell production for diabetes research and therapies.