Pancreatic function and diabetes

Multi-modal comparison of primary and stem cell-derived β-cells nominates targets for maturation

This study compares immature stem-cell-derived β-cells to primary β-cells using multi-omic single-cell methods, identifying SREBP1 as a target for improving β-cell maturation.

Diabetes-associated MYT1 and MYT3 regulate human beta-cell insulin secretion and survival via other diabetes-risk genes

This study shows MYT1 and ST18 regulate human beta-cell survival and insulin secretion under normal and stress conditions, with their genes enriched for T2D-risk loci.

Donor Macrophage Depletion Permits Post-Transplant Tolerance Induction in a Murine Islet Transplant Model

This study shows that depleting donor macrophages in islets allows tolerance induction through post-transplant donor cell infusions in a murine model.

Epigenetic Profiling of Human Insulinomas Reveals AP-1 Family as Critical Regulators of Beta Cell Maturation

The paper identifies AP-1 family transcription factors as critical regulators of beta cell maturation by analyzing epigenomic and transcriptomic profiles of human insulinomas.

Distinct senescent β-cell senotypes differentially drive islet aging and dysfunction

The paper identifies two distinct senescent β-cell subpopulations with different functional roles in islet aging and dysfunction using single-cell proteomics and transcriptomics.

ALPHA/BETA HYDROLASE DOMAIN CONTAINING 5 SUPPORTS GLUCOSE-STIMULATED-LIPOLYSIS AND INSULIN SECRETION IN PANCREATIC BETA CELLS

This study identifies ABHD5 as a critical co-activator of PNPLA2 in pancreatic beta cells, showing it supports glucose-stimulated lipolysis and insulin secretion.

Scinderin-driven Golgi Actin Remodeling coordinates GLP-1 and insulin secretion to regulate glucose homeostasis

This study identifies Scinderin as a regulator of Golgi actin remodeling that coordinates GLP-1 and insulin secretion, linking intracellular trafficking defects to glucose homeostasis and diabetes.

Inter-organ communication shapes human metabolic tissue states and resolves anti-diabetic drug response modes in a six-tissue microphysiological system

This study develops a six-tissue microphysiological system to investigate how inter-organ communication and nutrient conditions influence metabolic tissue states and drug responses to anti-diabetic therapies.

Loss of PAX4 results in disrupted endocrine pancreas development and neonatal diabetes in pigs

This paper shows that losing PAX4 in pigs causes severe diabetes and pancreatic issues, providing a model for studying PAX4's role in diabetes.

High-purity stem cell-derived β-cells recapitulate key transcriptional and functional features of human islets

This study develops a scalable method to produce high-purity stem cell-derived β-cells that closely mimic human islets in function and transcriptional profile.

The Recovery-Burden Index for Assessing Beta-Cell Function from OGTT Glucose Profiles

The paper develops the Recovery-Burden Index (RBI), a glucose-only metric from OGTT profiles that accurately predicts DI and detects beta-cell dysfunction.

Integrated histological and proteomic mapping of pancreatic adaptations during porcine pregnancy

This study characterizes pancreatic adaptations during porcine pregnancy, identifying new protein targets involved in endocrine cell remodeling and highlighting potential therapeutic targets for gestational diabetes.

Morning Elevation in Insulin Enhances Afternoon Hepatic Glucose Disposal in Dogs by Increasing Both Insulin Signaling and Glucose Action

This study shows that morning insulin exposure enhances afternoon hepatic glucose disposal in dogs by increasing glucose-mediated mechanisms, though maximal effects also require elevated afternoon insulin.

Workload-induced changes to cell state contribute to β-cell failure in diabetes

This study shows workload-induced β-cell overstimulation leads to failure in T2D, identifying a compensating transcriptional state and the role of Lsd1 in restraining state transitions.

Stromal and Neuronal Sources of Slit2/3 Ligands in the Adult Pancreas Exhibit Distinct Expression Patterns Independent of Robo2 Receptor Expression in the Islet

The paper identifies distinct cellular sources of Slit2/3 in the adult pancreas and shows their expression dynamics are independent of Robo2 receptor expression in islet cells.

Supervised machine learning identifies impaired mitochondrial quality control in β cells with development of type 2 diabetes

The paper uses supervised machine learning to identify impaired mitochondrial quality control in β cells associated with type 2 diabetes using single-cell RNA sequencing data.

Optimizing Post-Transplantation Detection of Subcutaneously Transplanted Islets Using Dithizone Staining

This study evaluates dithizone staining for localizing subcutaneously transplanted islets in mice, showing it reliably identifies insulin-producing β-cells and enables consistent dosing.

Fatty acids from adipocyte lipolysis stimulate insulin secretion

This study shows that fatty acids from adipocyte lipolysis stimulate insulin secretion via FFAR4 and FFAR1 receptors, highlighting adipose-islet crosstalk in metabolic regulation.

Heterogeneous endocrine cell composition defines human islet functional phenotypes

In 299 islet preparations from donors without diabetes, endocrine cell composition, not donor demographics, tracked insulin secretion, and δ cell percentage rose with type 2 diabetes genetic risk.

Divergent Cell-Type Specific Hypoxia Responses in Human Stem Cell-Derived and Primary Islets

This study compares the hypoxia response of stem cell-derived and primary human islets using single-cell transcriptomics, revealing divergent metabolic and apoptotic responses.

Structural Co-optation and Loss-of-function Underlie the Evolution of Regulatory Novelty in the Glucokinase Regulatory Protein

This study identifies a single mutation that enables GKRP to gain small-molecule allostery through structural co-optation, without requiring new genetic material.

Expansion microscopy reveals insulin granule clustering in human β-cells in type 2 diabetes

This study uses expansion microscopy to analyze insulin granule organization in human β-cells, finding increased clustering in type 2 diabetes without significant granule depletion.

5'tRNA-derived fragments modulate β-cell homeostasis and islet macrophage activation in type 2 diabetes

This study identifies 5'tRNA-derived fragments as mediators of β-cell dysfunction and islet macrophage activation in type 2 diabetes.

Stem-Cell-Derived Islets as a Model of Human Islet Inflammation: A Comparative Analysis of Pro-inflammatory Cytokine Responses

This study compares the response of stem-cell-derived islets to pro-inflammatory cytokines with primary human islets and EndoC-{beta}H5 cells, showing similar functional and transcriptomic changes.

Human and mouse regenerative macrophages enhance beta cell survival, function, and proliferation

This study shows regenerative macrophages enhance beta cell survival, function, and proliferation in vitro through contact-independent mechanisms and promote a regenerative macrophage phenotype.

Bridging scale-up to transplantation: pluripotent stem cell-derived pancreatic islet encapsulation in emulsion-generated high concentration alginate beads

This study develops a scalable encapsulation method for pluripotent stem cell-derived pancreatic islets, showing improved cell recovery and in vivo functionality during transplantation.

Morning Glucagon Disrupts Insulin Induced Hepatic Metabolic Memory and Subsequent Afternoon Glucose Metabolism in Canines

This study investigates whether morning hyperglucagonemia affects the priming effects of morning hyperinsulinemia on subsequent hepatic glucose metabolism in dogs.

Clinical grade cryopreservation unlocks transplant ready human pancreatic and stem cell derived islets for diabetes therapy

CryoMesh enables long-term clinical-scale preservation of human pancreatic and stem cell-derived islets with maintained function and viability for diabetes therapy.

Dielectrophoresis Reveals Stimulus-Induced Remodeling of Insulin Granule Subpopulations

This paper uses dielectrophoresis to separate insulin granule subpopulations and shows they change in response to insulinotropic signals.

Lag phase length of IAPP amyloid formation predicts the duration of β-cell toxicity

The paper links IAPP amyloid aggregation kinetics to β-cell toxicity duration, showing lag phase length predicts toxicity onset and duration across multiple conditions.