Related Experiment Video
Updated: May 17, 2026
10:12
Differentiation of Human Pluripotent Stem Cells Into Pancreatic Beta-Cell Precursors in a 2D Culture System
Published on: December 16, 2021
From genotype to human β cell phenotype and beyond.
Piero Marchetti1, Farooq Syed, Mara Suleiman
1Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy. piero.marchetti@med.unipi.it
Islets
|October 18, 2012
Summary
Genetic variations influence type 2 diabetes mellitus (T2DM) primarily through effects on beta cell function. This review explores how T2DM gene polymorphisms impact human islet cells, considering clinical relevance and epigenetics.
Area of Science:
- Endocrinology
- Genetics
- Metabolic Diseases
Background:
- Type 2 diabetes mellitus (T2DM) is a complex, polygenic condition influenced by genetic and environmental factors.
- Numerous genes and loci have been linked to T2DM, with many implicated in beta cell dysfunction.
- Understanding the genetic basis of T2DM is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To review and discuss the direct effects of polymorphisms in T2DM-associated genes on human islet cell properties.
- To explore the clinical implications of these genetic variations in T2DM.
- To examine the role of epigenetic mechanisms in T2DM pathogenesis.
Main Methods:
- Literature review of studies investigating T2DM-associated gene polymorphisms.
- Analysis of research on the functional impact of these polymorphisms on human islet cells.
- Synthesis of information regarding clinical relevance and epigenetic factors.
Main Results:
- Polymorphisms in T2DM-associated genes significantly alter human islet cell function, particularly beta cell properties.
- These genetic variations have direct clinical implications for T2DM risk and progression.
- Epigenetic mechanisms play a role in modulating the effects of T2DM-associated genes.
Conclusions:
- Genetic polymorphisms in T2DM-associated loci directly impact human islet cell function, contributing to disease pathogenesis.
- The interplay of genetics, environment, and epigenetics is central to T2DM development.
- Further research into these mechanisms can inform T2DM prevention and treatment.
Related Concept Videos
01:27Glucose 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 and C-peptide are co-secreted in...
01:26Type 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...
01:28Forced Transdifferentiation
Transdifferentiation, also known as lineage reprogramming, was first discovered by Selman and Kafatos in 1974 in silkmoths. They observed that the moths’ cuticle-producing cells transformed into salt-producing cells. Many such cases of natural transdifferentiation occur in organisms. In humans, pancreatic alpha cells can become beta cells. In newts, the loss of the eye’s lens causes the pigmented epithelial cells to transdifferentiate into the lens cells.
Artificial transdifferentiation occurs...
Artificial transdifferentiation occurs...
01:24Type II Diabetes II: Pathophysiology
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.
01:12Type I Diabetes I: Introduction
Type 1 diabetes mellitus is a chronic metabolic disorder characterized by an absolute deficiency of insulin resulting from the autoimmune destruction of pancreatic β-cells. Although it can occur at any age, it is most commonly diagnosed in childhood, adolescence, or early adulthood. The loss of insulin production impairs cellular glucose uptake, resulting in persistent hyperglycemia and necessitating lifelong insulin therapy.Autoimmune Destruction of β-CellsThe hallmark of type 1 diabetes is an...
02:27Background and Environment Affect Phenotype
Although the genetic makeup of an organism plays a major role in determining the phenotype, there are also several environmental factors, such as temperature, oxygen availability, presence of mutagens, that can alter an organism’s phenotype.
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...
An example of how genetic background affects phenotype can be seen in horses. The Extension gene in horses is responsible for their coat color. A wild-type gene (EE) produces black pigment in the coat, while a mutant gene (ee) produces red pigment. A...