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Glucose Homeostasis: Regulation of Blood Glucose01:02

Glucose Homeostasis: Regulation of Blood Glucose

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Carbohydrates consumed through foods are converted into glucose, a crucial energy source for the body. In the prandial state, high blood glucose levels stimulate the secretion of insulin from the pancreas. Insulin inhibits hepatic glucose production and stimulates glucose uptake and metabolism by muscle and adipose tissue. The excess glucose is converted into glycogen and stored in the liver and muscles.
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Glucose Transporters01:27

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Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
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Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

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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.
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Genetic Screens02:46

Genetic Screens

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Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing  genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
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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.
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A Glucose-Sensing Toggle Switch for Autonomous, High Productivity Genetic Control.

William Bothfeld1, Grace Kapov1, Keith E J Tyo1

  • 1Department of Chemical and Biological Engineering, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.

ACS Synthetic Biology
|March 10, 2017
PubMed
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Scientists engineered a glucose-sensing toggle switch for decoupled cell growth and product biosynthesis. This metabolic engineering tool enables autonomous activation of production pathways, improving efficiency and reducing costs.

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PHB productiongenetic toggle switchglucose sensingmetabolic engineering

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Area of Science:

  • Metabolic Engineering
  • Synthetic Biology
  • Biotechnology

Background:

  • Biosynthetic strategies often link product formation to cell growth, leading to limitations like feedstock diversion to biomass and toxicity management.
  • Existing methods for controlling gene expression in metabolic engineering can be costly, requiring specific inducers.

Purpose of the Study:

  • To develop a novel toggle switch for decoupling cell growth and product biosynthesis phases.
  • To enable autonomous, inducer-free activation of production pathways using a glucose-sensing mechanism.

Main Methods:

  • Engineered a glucose-sensing genetic toggle switch responsive to temporary glucose starvation.
  • Demonstrated autonomous activation of product pathway expression in both rich and minimal media.
  • Validated the system's stability, showing sustained expression after glucose reintroduction.

Main Results:

  • The glucose toggle switch successfully decoupled growth and production phases.
  • Temporary glucose starvation precisely triggered product pathway expression without external inducers.
  • The system maintained stability, with sustained expression even after glucose was reintroduced.
  • In polyhydroxybutyrate (PHB) biosynthesis, the strategy led to shorter growth phases and comparable product titers to constitutive expression systems.

Conclusions:

  • The developed glucose toggle switch provides a robust and cost-effective method for implementing two-phase production strategies in metabolic engineering.
  • This inducer-free, autonomous system offers broad applicability for controlling genetic programs in various biotechnological applications.