Pancreatic function and diabetes

DI/cle, a Measure Consisting of Insulin Sensitivity, Secretion, and Clearance, Captures Diabetic States

The paper introduces DI/cle, a new index combining insulin sensitivity, secretion, and clearance, showing it is impaired in T2DM but not in IGT.

The HDAC inhibitor trichostatin A impairs pancreatic β-cell function through an epigenome-wide reprogramming

This study shows that HDAC inhibition by trichostatin A disrupts β-cell function and identity through epigenome-wide remodeling in both mouse and human β-cell models.

Sorting receptor SORCS2 facilitates a protective stress response in pancreatic islets

This study identifies SORCS2's role in pancreatic islet stress response, showing its importance in glucose-stimulated insulin release and metabolic health.

AT7867 promotes pancreatic progenitor differentiation of human iPSCs and accelerates diabetes reversal

The paper shows that AT7867 increases pancreatic progenitor cell differentiation and accelerates diabetes reversal in mice.

Single-cell chromatin accessibility of developing murine pancreas identifies cell state-specific gene regulatory programs

This study uses single-nucleus ATAC-sequencing to analyze chromatin accessibility and RNA expression in developing mouse pancreas, identifying gene regulatory programs and transcription factors involved in cell fate determination.

Rab11 is essential to pancreas morphogenesis, lumen formation and endocrine mass.

This study shows Rab11 is essential for pancreas development, lumen formation, and endocrine mass by regulating epithelial morphogenesis and vesicle trafficking.

XBP1 expression in pancreatic islet cells is associated with poor glycaemic control across ancestries especially in young non-obese onset diabetes

This study identifies XBP1 expression in pancreatic islets as a genetic factor associated with poor glycaemic control and increased T2DM risk in South and East Asians, particularly in young non-obese onset diabetes.

A comprehensive map of human glucokinase variant activity

This study maps human glucokinase variant activity using a yeast complementation assay, identifying activity patterns linked to disease and providing insights for variant interpretation and therapeutic development.

Deoxyhypusine synthase is required for the translational regulation of pancreatic beta cell maturation

This study identifies DHPS/eIF5A as a gatekeeper of mRNA translation in pancreatic beta cells, showing its essential role in beta cell maturation and function, with DHPS deficiency leading to diabetes.

Tracking insulin- and glucagon-expressing bihormonal cells during differentiation using an INSULIN and GLUCAGON double reporter human embryonic stem cell line

The paper develops a dual fluorescent reporter hESC line to track insulin- and glucagon-expressing cells during differentiation, revealing bihormonal cells preferentially become alpha-like.

Insulin secretion deficits in a Prader-Willi syndrome β-cell model are associated with a concerted downregulation of multiple endoplasmic reticulum chaperones

This study identifies a reduction in ER chaperones in PWS β-cells, leading to impaired insulin secretion and ER stress.

Chromatin accessibility differences between alpha, beta, and delta cells identifies common and cell type-specific enhancers

Compromised beta-cell identity in type 2 diabetes

The paper develops a mathematical model to study how chronic hyperglycemia affects beta-cell transcription factors PDX1 and MAFA, identifying FOXO1 as a potential therapeutic target for restoring beta-cell identity.

A Consensus Model of Glucose-Stimulated Insulin Secretion in the Pancreatic beta-Cell

The paper develops a consensus model of glucose-stimulated insulin secretion in pancreatic beta-cells using a systematic workflow, showing glucose-dependent increases in glycolytic intermediates and ATP/ADP ratios drive insulin secretion.

Acinar-ductal cell rearrangement drives pancreas branching morphogenesis in an IGF/PI3K-dependent manner

The paper identifies acinar-ductal cell rearrangements driven by the IGF/PI3K pathway as a mechanism for pancreas branching morphogenesis while preserving acinar-ductal unit integrity.

Cystine/glutamate antiporter system Xc- deficiency impairs insulin secretion.

This study shows that Slc7a11 deficiency reduces glutathione levels and impairs insulin secretion in beta-cells but not in islet macrophages.

FOXM1 acts sexually dimorphically to regulate functional β-cell mass

This study shows FOXM1 regulates β-cell function differently in males and females, with estrogen receptor mediating female-specific effects on glucose tolerance and β-cell mass.

DNA methylation Dependent Restriction of Tyrosine Hydroxylase Contributes to Pancreatic β-cell Heterogeneity

This study identifies DNA methylation as a mechanism restricting TH+ β-cell subpopulation in pancreatic islets, showing its role in β-cell heterogeneity and identity maintenance.

Spatial molecular imaging of the human type 2 diabetic islet

This study uses spatial molecular imaging to analyze transcriptomic changes in human islets during the progression from obesity to type 2 diabetes, identifying novel transcriptomic profiles in alpha cells.

Integration of single-cell multiomic measurements across disease states with genetics identifies mechanisms of beta cell dysfunction in type 2 diabetes

The paper integrates single-cell multiomic data with genetics to identify gene regulatory changes in beta cells associated with type 2 diabetes.

A genome-wide CRISPR screen identifies regulators of beta cell function involved in type 2 diabetes risk

A genome-wide CRISPR screen in human pancreatic beta cells identifies 580 genes influencing insulin content, supporting 20 candidate type 2 diabetes effector transcripts.

Single cell transcriptomic and spatial landscapes of the developing human pancreas

This study integrates single-cell RNA sequencing and spatial transcriptomics to map the temporal-spatial gene expression patterns during human pancreas development, identifying lineage dynamics and novel genes involved in beta cell maturation.

Identification of a unique transcriptomic signature associated with islet amyloidosis

This study identifies transcriptomic changes in islet amyloidosis using RNA sequencing and finds a gene co-expression module linked to the condition.

Arid1a loss potentiates pancreatic β-cell regeneration through activation of EGF signaling

This study shows that Arid1a loss enhances pancreatic β-cell regeneration by activating EGF signaling, protecting against diabetes.

A novel disease mechanism leading to the expression of a disallowed gene in the pancreatic beta-cell identified by non-coding, regulatory mutations controlling HK1

The paper identifies non-coding mutations in a regulatory element of HK1 that lead to inappropriate expression in pancreatic beta-cells and cause congenital hyperinsulinism.

Chemical induction of gut β-like-cells by combined FoxO1/Notch inhibition as a glucose-lowering treatment for diabetes

The paper shows that a small molecule FoxO1 inhibitor generates gut β-like cells, improving glucose tolerance in diabetes models.

Kinetic and data-driven modeling of pancreatic β-cell central carbon metabolism and insulin secretion

This paper develops a kinetic and data-driven model of pancreatic β-cell metabolism to understand its role in glucose-stimulated insulin secretion and predict therapeutic interventions.

HNF1α transcriptional activation and repression maintain human islet α and β cell function

This study investigates how HNF1A regulates human islet cell function by combining genetic, transcriptomic, and functional assays, revealing its role in maintaining insulin and glucagon secretion.

Toward Improving Immunotolerance for Stem Cell-Derived Islets

The paper demonstrates that transplanting human stem cell-derived islets into the mouse testis induces immune tolerance through suppressive cytokines and regulatory T cells, improving islet survival.

Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunction

This study shows that gut-derived bacterial flagellin contributes to beta-cell inflammation and dysfunction in type 2 diabetes.