Related Experiment Video

Updated: Jun 15, 2026

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
08:34

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis

Published on: June 3, 2016

FOXO3a governs early and late apoptotic endothelial programs during elevated glucose through mitochondrial and

Jinling Hou1, Zhao Zhong Chong, Yan Chen Shang

  • 1Division of Cellular and Molecular Cerebral Ischemia, Wayne State University School of Medicine, Detroit, MI 48201, USA.

Molecular and Cellular Endocrinology
|March 10, 2010
PubMed

Insights

Akt1 and FoxO3a are crucial for endothelial cell apoptosis in diabetes. Targeting these pathways may offer new treatments for impaired glucose tolerance and diabetes mellitus.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Endocrinology

Background:

  • Endothelial cell (EC) integrity is vital for managing endocrine disorders like diabetes mellitus (DM).
  • Mechanisms protecting ECs are not fully understood, hindering therapeutic development.
  • Elevated glucose levels pose a significant threat to ECs.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying endothelial cell apoptosis in response to high glucose.
  • To identify key proteins and pathways involved in EC survival and death signaling.
  • To explore potential therapeutic targets for diabetes-related vascular complications.

Main Methods:

  • Primary cerebral endothelial cells were used in a model of elevated d-glucose.
  • Investigated the role of Akt1 and the forkhead transcription factor FoxO3a.
  • Utilized gene knockdown to assess the necessity of FoxO3a in apoptotic pathways.
  • Monitored mitochondrial membrane potential and cytochrome c release.
  • Assessed caspase activation, including caspase 1 and 3.

Main Results:

  • Akt1 and FoxO3a are critical for early apoptotic signaling in ECs under high glucose conditions.
  • FoxO3a regulates nuclear DNA degradation and mitochondrial apoptotic pathways.
  • FoxO3a is essential for preventing mitochondrial depolarization and cytochrome c release.
  • FoxO3a is necessary for the activation of caspase 1 and 3.
  • Loss of FoxO3a significantly inhibits the apoptotic cascade.

Conclusions:

  • Akt1 and FoxO3a are key regulators of the apoptotic cascade in endothelial cells exposed to high glucose.
  • These proteins and their associated pathways represent promising therapeutic targets for diabetes mellitus and impaired glucose tolerance.
  • Understanding these mechanisms can lead to novel strategies for preserving endothelial function in diabetic patients.

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

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 hydroxylase and factor...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Glucose Homeostasis: Regulation of Blood Glucose01:02

Glucose Homeostasis: Regulation of Blood Glucose

Carbohydrates consumed through foods are converted into glucose, a crucial energy source for the body. In the prandial state, high blood glucose levels stimulate the secretion of insulin from the pancreas. Insulin inhibits hepatic glucose production and stimulates glucose uptake and metabolism by muscle and adipose tissue. The excess glucose is converted into glycogen and stored in the liver and muscles.
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...