Insulin granule biogenesis and exocytosis

M Omar-Hmeadi, O Idevall-Hagren - Cellular and Molecular Life Sciences, 2021 - Springer
Insulin is produced by pancreatic β-cells, and once released to the blood, the hormone
stimulates glucose uptake and suppresses glucose production. Defects in both the …

Metabolic and functional specialisations of the pancreatic beta cell: gene disallowance, mitochondrial metabolism and intercellular connectivity

GA Rutter, E Georgiadou, A Martinez-Sanchez… - Diabetologia, 2020 - Springer
All forms of diabetes mellitus involve the loss or dysfunction of pancreatic beta cells, with the
former predominating in type 1 diabetes and the latter in type 2 diabetes. Deeper …

Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation

A Mahajan, CN Spracklen, W Zhang, MCY Ng… - Nature …, 2022 - nature.com
We assembled an ancestrally diverse collection of genome-wide association studies
(GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls …

Type 2 diabetes genetic loci informed by multi-trait associations point to disease mechanisms and subtypes: a soft clustering analysis

MS Udler, J Kim, M von Grotthuss… - PLoS …, 2018 - journals.plos.org
Background Type 2 diabetes (T2D) is a heterogeneous disease for which (1) disease-
causing pathways are incompletely understood and (2) subclassification may improve …

Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes

A Mahajan, J Wessel, SM Willems, W Zhao… - Nature …, 2018 - nature.com
We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls
of diverse ancestry, identifying 40 coding variant association signals (P< 2.2× 10− 7); of …

Genome-wide discovery of genetic loci that uncouple excess adiposity from its comorbidities

LO Huang, A Rauch, E Mazzaferro, M Preuss… - Nature …, 2021 - nature.com
Obesity is a major risk factor for cardiometabolic diseases. Nevertheless, a substantial
proportion of individuals with obesity do not suffer cardiometabolic comorbidities. The …

Single-cell chromatin accessibility identifies pancreatic islet cell type–and state-specific regulatory programs of diabetes risk

J Chiou, C Zeng, Z Cheng, JY Han, M Schlichting… - Nature …, 2021 - nature.com
Single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-
seq) creates new opportunities to dissect cell type–specific mechanisms of complex …

Multi-omics profiling of living human pancreatic islet donors reveals heterogeneous beta cell trajectories towards type 2 diabetes

L Wigger, M Barovic, AD Brunner, F Marzetta… - Nature …, 2021 - nature.com
Most research on human pancreatic islets is conducted on samples obtained from
normoglycaemic or diseased brain-dead donors and thus cannot accurately describe the …

Genetic variant effects on gene expression in human pancreatic islets and their implications for T2D

A Viñuela, A Varshney, M van de Bunt… - Nature …, 2020 - nature.com
Most signals detected by genome-wide association studies map to non-coding sequence
and their tissue-specific effects influence transcriptional regulation. However, key tissues …

High-throughput genetic clustering of type 2 diabetes loci reveals heterogeneous mechanistic pathways of metabolic disease

H Kim, KE Westerman, K Smith, J Chiou, JB Cole… - Diabetologia, 2023 - Springer
Aims/hypothesis Type 2 diabetes is highly polygenic and influenced by multiple biological
pathways. Rapid expansion in the number of type 2 diabetes loci can be leveraged to …