Related Experiment Video
Updated: Apr 19, 2026
08:34
Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
15.9K
Moderate hypoxia induces β-cell dysfunction with HIF-1-independent gene expression changes
Yoshifumi Sato1, Masahiro Inoue2, Tatsuya Yoshizawa1
1Department of Medical Biochemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Plos One
|December 16, 2014
Summary
Moderate hypoxia impairs pancreatic beta-cell function and survival by downregulating key genes and inducing apoptosis. This highlights hypoxia as a critical stressor in type 2 diabetes progression.
Area of Science:
- Endocrinology
- Cell Biology
- Diabetes Research
Background:
- Pancreatic beta-cell dysfunction is central to type 2 diabetes.
- Previous work showed beta-cells become hypoxic under high glucose and diabetic mice islets are hypoxic.
- The effect of moderate hypoxia on beta-cell number and function remained unclear.
Purpose of the Study:
- To investigate the impact of moderate hypoxia on pancreatic beta-cell function and survival.
- To determine the role of hypoxia-inducible factor 1-alpha (HIF-1α) in hypoxia-induced beta-cell changes.
Main Methods:
- MIN6 cells and isolated pancreatic islets were exposed to moderate hypoxia.
- Hypoxic response was assessed by measuring HIF-1α protein and target gene expression.
- Gene expression of key beta-cell markers was analyzed.
- Insulin secretion and apoptosis were evaluated under hypoxic conditions.
Main Results:
- Moderate hypoxia induced a hypoxic response in MIN6 cells, increasing HIF-1α levels.
- Hypoxia led to downregulation of crucial beta-cell genes including Mafa, Pdx1, and Ins1.
- Abnormal insulin secretion and increased apoptosis were observed in hypoxic MIN6 cells.
- Most gene downregulation occurred independently of HIF-1α suppression.
Conclusions:
- Hypoxia acts as a novel stressor for pancreatic beta-cells.
- Hypoxic stress contributes to beta-cell dysfunction and may play a role in type 2 diabetes progression.
- A HIF-1-independent mechanism is involved in hypoxia-induced gene downregulation in beta-cells.
More Related Videos
Related Concept Videos
01:58Cell Specific Gene Expression
17.5K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
17.5K
01:24Regulation of Angiogenesis and Blood Supply
4.0K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
4.0K
01:24Type II Diabetes II: Pathophysiology
2
PathophysiologyType 2 diabetes mellitus (T2DM ) is a chronic metabolic disorder characterized by insulin resistance and progressive pancreatic β-cell dysfunction, leading to impaired glucose homeostasis. It results from interactions among genetic predisposition, environmental factors, and metabolic stressors, such as overnutrition and a sedentary lifestyle.Insulin Resistance and Glucose DysregulationEarly T2DM involves insulin resistance in skeletal muscle, adipose tissue, and the liver.
2
01:23Hypoxia
2.7K
Hypoxia is a medical condition characterized by an inadequate oxygen supply to body tissues. It typically manifests as a bluish discoloration of the skin and mucosae, especially in fair-skinned individuals, when hemoglobin (Hb) saturation drops below 75%.
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...
2.7K
01:26Type I Diabetes II: Pathophysiology
6
Type 1 diabetes mellitus arises from an immune-mediated destruction of pancreatic β-cells, resulting in an absolute deficiency of insulin. This process develops in genetically susceptible individuals when autoimmunity, environmental exposures, and immunologic dysregulation converge to trigger a targeted attack on the insulin-producing cells of the pancreas. The β-cells are located within the islets of Langerhans and are essential for regulating blood glucose by facilitating cellular...
6
01:26Type II Diabetes I: Introduction
2
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance, in which target tissues such as the liver, muscle, and adipose tissue respond poorly to insulin. It is also associated with inadequate compensatory insulin secretion, where pancreatic β-cells fail to produce sufficient insulin. Together, these abnormalities lead to persistent hyperglycemia.EtiologyT2DM develops through a complex interaction of genetic predisposition and environmental or...
2