Related Experiment Video
Updated: Jan 7, 2026
10:09
Leprdb Mouse Model of Type 2 Diabetes: Pancreatic Islet Isolation and Live-cell 2-Photon Imaging Of Intact Islets
Published on: May 11, 2015
10.0K
Single-cell perturbations decipher ribosomal stress-surveillance regulators in type 2 diabetes
Jingminjie Nan1, Xianglong He1, Xiaoping Liu2
1Ruijin Yangtze River Delta Health Institute, Wuxi Branch of Ruijin Hospital, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Nature Metabolism
|January 2, 2026
Summary
Researchers used Perturb-seq to identify genes impacting type 2 diabetes (T2D). They found ZZEF1 regulates insulin production and beta-cell stress, offering potential therapeutic targets for T2D.
Area of Science:
- Genomics
- Molecular Biology
- Endocrinology
Background:
- Type 2 Diabetes (T2D) genetic architecture requires scalable functional genomics.
- CRISPR perturbations reveal mechanistic effects of underexplored genes.
Purpose of the Study:
- Systemically characterize genes and pathways in T2D genetic architecture.
- Investigate insulin production and T2D pathology in human pancreatic beta cells.
Main Methods:
- Performed single-cell RNA sequencing on pooled CRISPR screens (Perturb-seq).
- Screened 61 T2D-associated genes and 40 ribosome-associated quality control (RQC) genes.
- Utilized human pancreatic beta cells (EndoC-βH1), knockout mice, islet organoids, and human islets.
Main Results:
- Identified 21 functional genes, including uncharacterized KLHL42 and ZZEF1.
- ZZEF1 regulates insulin synthesis and beta-cell stress via ribosomal stress-surveillance pathways.
- ZZEF1 deficiency impairs beta-cell function by inhibiting EDF1, treatable with azoramide and ISRIB.
Conclusions:
- Perturb-seq identified functional RQC-related genes.
- ZZEF1 is a key regulator of beta-cell function and stress.
- Identified potential therapeutic targets for T2D.
Related Concept Videos
01:29Translational Regulation
503
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
503
01:19Psychoneuroimmunology: Diabetes and Cancer
404
Chronic stress has been linked to both the onset and progression of serious health conditions, including Type 2 diabetes and cancer. Type 2 diabetes, a widespread chronic illness, is closely associated with obesity and insulin resistance, both of which often worsen under stress. Studies indicate that men experiencing high levels of chronic stress face a 45% higher risk of developing diabetes compared to those with minimal stress. Stress triggers physiological responses that elevate blood...
404
01:22Diabetes Mellitus: Type 2 and Gestational
4.2K
Type 2 diabetes, characterized by insulin resistance, arises when the insulin receptors on cells lose responsiveness to insulin, diminishing the cell's capacity to take up glucose, resulting in elevated blood glucose levels. To receive a diagnosis of Type 2 diabetes, a series of blood glucose tests are necessary to assess whether the blood glucose falls within normal parameters. If the result is out of the normal range, a patient may be diagnosed as prediabetic or diabetic, depending on the...
4.2K
01:31Regulation of the Unfolded Protein Response
2.9K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.9K
01:22Diabetes Mellitus: Overview and Type I Subtype
4.8K
Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels due to inadequate insulin production, insulin resistance, or both. The condition affects millions worldwide and can significantly impact their health and quality of life.
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
4.8K
01:36Carbohydrate Metabolism
13.7K
Carbohydrates are polymers composed of molecules containing atoms of carbon, hydrogen and oxygen. One gram of carbohydrate can provide four kilo-calories of energy, which makes it the most efficient instant energy source.
Starch accounts for approximately 60% of the carbohydrates consumed by humans. Since amylase enzymes cannot function in the stomach's acidic environment, starch can only be digested in the mouth and small intestine. Simple sugars are found naturally in milk and fruits in...
Starch accounts for approximately 60% of the carbohydrates consumed by humans. Since amylase enzymes cannot function in the stomach's acidic environment, starch can only be digested in the mouth and small intestine. Simple sugars are found naturally in milk and fruits in...
13.7K