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Related Concept Videos

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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Glucose Homeostasis: Regulation of Blood Glucose01:02

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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

Glucose Transporters

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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.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
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Insulin Secretory Vesicles01:05

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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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Insulin: The Receptor and Signaling Pathways01:28

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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...
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Insulin Formulations: Types and Delivery01:27

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Insulin preparations are categorized by their duration of action into short-acting and long-acting types. Two strategies are used to modify insulin's absorption and pharmacokinetic profile: slowing the absorption post-subcutaneous injection, or altering human insulin's amino acid sequence or protein structure. These changes retain the insulin's ability to bind to the insulin receptor, but alter its behavior in solution or after injection.
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Glucose-Responsive Insulin Through Bioconjugation Approaches.

Maria M Disotuar1, Diao Chen1, Nai-Pin Lin1

  • 1Department of Biochemistry, University of Utah, Salt Lake City, UT, USA.

Journal of Diabetes Science and Technology
|June 21, 2019
PubMed
Summary

Researchers are developing glucose-responsive insulin (GRI) bioconjugates to improve diabetes management. This innovative approach aims for better glycemic control and reduced hypoglycemia risk without external devices.

Keywords:
bioconjugateglucose-responsive insulinglycemic controlhypoglycemia

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Area of Science:

  • Bioconjugation Chemistry
  • Diabetes Therapeutics
  • Biomedical Engineering

Background:

  • Current insulin analogs offer improved glycemic control but have a narrow therapeutic window, risking hypoglycemia.
  • Maintaining normoglycemia is challenging due to the limitations of existing insulin therapies.
  • No FDA-approved insulins currently exist that self-regulate their activity based on blood glucose levels.

Purpose of the Study:

  • To review recent advancements in glucose-responsive insulin (GRI) bioconjugates.
  • To explore GRI development that does not require exogenous matrices.
  • To highlight the potential of GRI for enhanced diabetes management.

Main Methods:

  • Review of scientific literature on glucose-responsive insulin bioconjugates.
  • Analysis of strategies for creating insulin therapeutics regulated by blood glucose.
  • Discussion of progress in developing matrix-free GRI systems.

Main Results:

  • Significant progress has been made in developing glucose-responsive insulin (GRI) bioconjugates.
  • These bioconjugates show promise for achieving better glycemic control.
  • The approach demonstrates a potential reduction in the risk of severe hypoglycemia.

Conclusions:

  • Glucose-responsive insulin (GRI) bioconjugates represent a promising therapeutic strategy for diabetes.
  • Further development is needed to maximize glucose responsiveness and clinical utility.
  • Future research should focus on optimizing GRI systems for safe and effective glucose regulation.