Related Experiment Video

Updated: May 10, 2026

A High-content In Vitro Pancreatic Islet β-cell Replication Discovery Platform
09:35

A High-content In Vitro Pancreatic Islet β-cell Replication Discovery Platform

Published on: July 16, 2016

PTEN controls β-cell regeneration in aged mice by regulating cell cycle inhibitor p16ink4a

Ni Zeng1, Kai-Ting Yang, Jennifer-Ann Bayan

  • 1Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, 90089, USA.

Aging Cell
|July 6, 2013
PubMed

Insights

Aging reduces tissue regeneration due to declining growth factors like IGF-1. This study reveals PTEN loss in pancreatic cells prevents aging-related proliferation decline by inhibiting p16INK4a, restoring regeneration capacity.

Area of Science:

  • Cellular biology
  • Aging research
  • Endocrinology

Background:

  • Tissue regeneration capacity decreases with age, linked to reduced growth factors like insulin-like growth factor-1 (IGF-1).
  • Pancreatic beta-cell proliferation loss in aging contributes to diabetes pathogenesis.
  • The PI3K/AKT pathway, downstream of insulin/IGF-1 signaling, is crucial for cell growth and survival.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying age-related decline in pancreatic beta-cell regeneration.
  • To explore the role of PTEN (phosphatase and tensin homologue deleted on chromosome 10) in regulating beta-cell proliferation and regeneration during aging.
  • To identify novel signaling pathways involved in cellular senescence and the loss of regenerative capacity.

Main Methods:

  • Utilized a mouse model with genetic deletion of PTEN specifically in insulin-producing cells.
  • Employed various animal and cell models to manipulate PTEN expression.
  • Analyzed cell cycle regulation, gene expression (p16INK4a, cyclin D1), transcription factor activity (E2F), and epigenetic modifications (DNA methylation, Ezh2 activity).

Main Results:

  • Genetic deletion of PTEN in pancreatic beta-cells prevented the age-associated decline in proliferation.
  • PTEN loss restored the regenerative capacity of aged beta-cells following injury.
  • Identified a novel PTEN/cyclin D1/E2F/Ezh2/p16INK4a signaling network where PTEN normally promotes aging by upregulating p16INK4a, a cell cycle inhibitor.

Conclusions:

  • PTEN acts as a key regulator of cellular aging in pancreatic beta-cells by controlling the p16INK4a pathway.
  • The identified signaling network provides a molecular explanation for how declining growth factor signaling (e.g., IGF-1) contributes to impaired regeneration in aging cells.
  • Targeting this PTEN-mediated pathway may offer therapeutic strategies to enhance tissue regeneration and combat age-related diseases like diabetes.
Keywords:
PI3KPTENagingp16ink4aβ-cells

More Related Videos

In Vitro Colony Assays for Characterizing Tri-potent Progenitor Cells Isolated from the Adult Murine Pancreas09:31

In Vitro Colony Assays for Characterizing Tri-potent Progenitor Cells Isolated from the Adult Murine Pancreas

Published on: June 10, 2016

Surgical Injury to the Mouse Pancreas through Ligation of the Pancreatic Duct as a Model for Endocrine and Exocrine Reprogramming and Proliferation07:44

Surgical Injury to the Mouse Pancreas through Ligation of the Pancreatic Duct as a Model for Endocrine and Exocrine Reprogramming and Proliferation

Published on: August 7, 2015

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

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...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Tissue Renewal without Stem Cells01:23

Tissue Renewal without Stem Cells

After cellular or tissue damage, the resident stem cells present in the human body can locally repair and regenerate the damaged tissue or organ. However, even though some tissues do not have stem cells, they can repair and regenerate with the help of pre-existing cells. For example, beta cells of the pancreas and hepatocytes of the liver can divide to renew and regenerate the tissue. Here, both cell division and cell death are well regulated by homeostasis.
However, failure of such a system...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Replicative Cell Senescence02:15

Replicative Cell Senescence

Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...