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Related Concept Videos

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...
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...
Hormones Regulating Blood Glucose01:16

Hormones Regulating Blood Glucose

Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
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...

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Differentiation of Human Pluripotent Stem Cells into Insulin-Producing Islet Clusters
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A brief perspective on insulin production.

D F Steiner1, S-Y Park, J Støy

  • 1Department of Biochemistry, The University of Chicago, IL 60637, USA. dfsteine@uchicago.edu

Diabetes, Obesity & Metabolism
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Summary

Insulin is made from a precursor called proinsulin, processed by specific enzymes. Understanding this pathway reveals connections to diabetes and highlights the importance of beta cell health.

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Coculture Analysis of Extracellular Protein Interactions Affecting Insulin Secretion by Pancreatic Beta Cells

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05:51

Coculture Analysis of Extracellular Protein Interactions Affecting Insulin Secretion by Pancreatic Beta Cells

Published on: June 15, 2013

Area of Science:

  • Biochemistry
  • Cell Biology
  • Endocrinology

Background:

  • Beta cells synthesize and release insulin, a mature molecule composed of A and B polypeptide chains.
  • Insulin is derived from a precursor, proinsulin, through proteolytic processing, a concept that reshaped understanding of hormone biosynthesis.
  • C-peptide, co-secreted with insulin, enables in vivo studies of pancreatic beta cell function, particularly in diabetes.

Purpose of the Study:

  • To review the biosynthesis of insulin from its precursor, proinsulin.
  • To highlight the enzymes involved in proinsulin processing.
  • To discuss the implications of (pro)insulin biosynthesis defects in diabetes pathogenesis and beta cell health.

Main Methods:

  • Review of historical discoveries in proinsulin processing.
  • Identification of key proteases (prohormone convertases, carboxypeptidase E) in insulin biosynthesis.
  • Analysis of recent studies on insulin gene mutations and their impact on protein folding and endoplasmic reticulum function.

Main Results:

  • Proinsulin is proteolytically processed into insulin and C-peptide by specific enzymes.
  • Defects in (pro)insulin biosynthesis are linked to diabetes pathogenesis.
  • Insulin gene mutations reveal critical residues affecting preproinsulin folding and processing.

Conclusions:

  • The discovery of proinsulin processing revolutionized hormone biosynthesis research.
  • Studies of (pro)insulin biosynthesis and processing provide insights into beta cell function and diabetes.
  • Endoplasmic reticulum function is crucial for insulin biosynthesis and maintaining beta cell health.