Related Experiment Video

Updated: May 27, 2026

High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds
12:32

High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds

Published on: January 23, 2018

Musashi expression in β-cells coordinates insulin expression, apoptosis and proliferation in response to endoplasmic

M Szabat1, T B Kalynyak, G E Lim

  • 1Department of Cellular and Physiological Sciences, Life Sciences Institute, Vancouver, BC, Canada.

Cell Death & Disease
|November 25, 2011
PubMed

Insights

Musashi genes regulate pancreatic beta-cell survival and proliferation. Musashi isoforms show distinct roles in insulin expression and are linked to endoplasmic reticulum stress in type 2 diabetes progression.

Area of Science:

  • Cell Biology
  • Endocrinology
  • Developmental Biology

Background:

  • Pancreatic beta-cell death and dysfunction are central to diabetes.
  • Musashi genes are known regulators of cell fate via Notch signaling.
  • Recent work implicated Notch signaling in beta-cell survival.

Purpose of the Study:

  • To investigate the role of Musashi isoforms in pancreatic beta-cells.
  • To determine the relationship between Musashi, endoplasmic reticulum stress, and beta-cell function in diabetes.
  • To elucidate the distinct functions of Musashi-1 and Musashi-2 in beta-cell regulation.

Main Methods:

  • Analysis of Musashi isoform expression in human and mouse islet cells.
  • Directed differentiation of human embryonic stem cells (hESCs) to pancreatic lineage.
  • Induction of endoplasmic reticulum stress and beta-cell dedifferentiation.
  • Overexpression and knockdown studies of Musashi isoforms (MSI1, MSI2).

Main Results:

  • Both Musashi isoforms (MSI1, MSI2) and Notch pathway components are expressed in adult islet cells.
  • Musashi expression is detected during human fetal development and hESC differentiation.
  • Endoplasmic reticulum stress increases Msi2 and Hes1, decreases insulin expression, linking ER stress to beta-cell dedifferentiation.
  • MSI1 overexpression promotes proliferation and Hes1, while inhibiting apoptosis and reducing insulin.
  • MSI2 overexpression decreases MSI1 expression, indicating distinct and overlapping roles.

Conclusions:

  • Musashi-1 and Musashi-2 have distinct yet overlapping roles in controlling beta-cell proliferation and insulin expression.
  • Musashi acts as a novel link between endoplasmic reticulum stress and beta-cell dedifferentiation/proliferation observed in type 2 diabetes progression.
  • These findings highlight Musashi as a potential therapeutic target for diabetes.

More Related Videos

Methods to Assess Beta Cell Death Mediated by Cytotoxic T Lymphocytes12:12

Methods to Assess Beta Cell Death Mediated by Cytotoxic T Lymphocytes

Published on: June 16, 2011

Isolated Pancreatic Islet Treatment and Apoptosis Measurement09:36

Isolated Pancreatic Islet Treatment and Apoptosis Measurement

Published on: May 2, 2025

Related Concept Videos

Type I Diabetes II: Pathophysiology01:26

Type I Diabetes II: Pathophysiology

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 uptake of...
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...
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

Glucose Homeostasis: Pancreatic Islets and Insulin Secretion

The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
Insulin and C-peptide are co-secreted in...
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but this inhibition is released...
Insulin Secretory Vesicles01:05

Insulin Secretory Vesicles

Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

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...