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Related Concept Videos

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 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...
Cells and Secretions of the Pancreas01:16

Cells and Secretions of the Pancreas

The pancreas, a vital organ within the abdominal cavity, plays dual roles in the digestive and endocrine systems, collaborating with exocrine and endocrine cells to maintain optimal digestion and blood sugar levels.
Exocrine function is carried out by acinar cells, organized into clusters known as acini. These cells contribute to digestion by releasing substantial quantities of enzyme-rich, alkaline digestive juices.
Concurrently, the dispersed clusters of endocrine cells throughout the...
Insulin: Biosynthesis, Chemistry, and Preparation01:25

Insulin: Biosynthesis, Chemistry, and Preparation

The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment primarily uses...
Production of Pharmaceuticals01:30

Production of Pharmaceuticals

Industrial insulin production uses genetically engineered E. coli expressing a proinsulin gene controlled by a tryptophan promoter and containing a methionine linker for later cleavage. The cells also carry ampicillin resistance for selective growth. Seed cultures are stored at −80 °C and production begins by thawing a small amount to inoculate starter cultures, which are progressively scaled to a 50,000-L bioreactor. In the bioreactor, E. coli grow in nutrient-rich media under sterile, tightly...
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...

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Differentiation of Human Pluripotent Stem Cells into Insulin-Producing Islet Clusters
08:41

Differentiation of Human Pluripotent Stem Cells into Insulin-Producing Islet Clusters

Published on: June 23, 2023

Size-controlled insulin-secreting cell clusters.

Adam D Mendelsohn1, Crystal Nyitray, Mark Sena

  • 1Joint Graduate Group in Bioengineering, University of California at San Francisco, San Francisco, CA 94158, USA.

Acta Biomaterialia
|August 21, 2012
PubMed
Summary

Controlling the size of pancreatic cell clusters is key for type I diabetes treatment. Uniformly sized clusters, particularly 100-120μm, show improved insulin secretion and viability for transplantation.

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Area of Science:

  • Biomedical Engineering
  • Regenerative Medicine
  • Endocrinology

Background:

  • Type I diabetes treatment via pancreatic beta-cell transplantation faces challenges with sub-optimal clinical outcomes.
  • Previous transplantation efforts lacked control over cluster size, impacting cell viability and insulin secretion.
  • Cluster size is a critical parameter influencing the therapeutic efficacy of transplanted beta-cells.

Purpose of the Study:

  • To develop a method for fabricating uniformly size-controlled insulin-secreting cell clusters.
  • To investigate the impact of cluster size on insulin expression, content, and secretion.
  • To identify optimal cluster sizes for enhanced efficacy in pancreatic beta-cell transplantation.

Main Methods:

  • Fabrication of uniformly size-controlled cell clusters using patterned laminin for covalent attachment.
  • Culturing of size-controlled beta-cell clusters within a specific diameter range (40-120μm).
  • Assessment of insulin expression, content, and glucose-stimulated insulin secretion in relation to cluster size.

Main Results:

  • Cluster size significantly affects insulin expression, content, and secretion.
  • Increasing cluster size from 40μm to 60μm enhances glucose-stimulated insulin production per cell.
  • Increasing cluster size beyond 60μm improves sustained glucose-stimulated insulin secretion per cell.

Conclusions:

  • A novel method for producing uniformly sized insulin-secreting cell clusters has been established.
  • Optimal cluster sizes (100-120μm) may enhance viability and efficacy for encapsulated beta-cell transplants.
  • Further in vivo evaluation is warranted to confirm the therapeutic potential for type I diabetes treatment.