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Related Concept Videos

Insulin Formulations: Types and Delivery01:27

Insulin Formulations: Types and Delivery

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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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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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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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Related Experiment Video

Updated: May 24, 2025

A Multi-Parametric Islet Perifusion System within a Microfluidic Perifusion Device
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Intermittent Low-Magnitude Pressure Applied Across Macroencapsulation Devices Enables Physiological Insulin Delivery

Ella A Thomson1, Sooyeon Lee2, Haixia Xu2

  • 1Department of Electrical Engineering, Stanford University, Stanford, CA.

Diabetes
|March 3, 2025
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Summary

Applying physiological pressure to macroencapsulated islets significantly enhances insulin delivery, overcoming diffusion limitations for type 1 diabetes treatment. This pressure-driven method enables precise glucose regulation and a potential path to insulin independence.

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Area of Science:

  • Biomedical Engineering
  • Endocrinology
  • Regenerative Medicine

Background:

  • Cellular macroencapsulation shows promise for type 1 diabetes treatment by isolating transplanted islets.
  • Current diffusion-based methods struggle with on-demand insulin delivery and physiological glucose control.
  • Existing macroencapsulation devices have not achieved insulin independence in clinical trials.

Purpose of the Study:

  • To investigate the potential of applying physiological pressure to enhance insulin transport across immunoisolation membranes.
  • To determine if pressure can overcome diffusion limitations for on-demand insulin delivery from macroencapsulated islets.
  • To validate a pressure-enhanced system for achieving physiological glucose regulation in diabetic models.

Main Methods:

  • Developed theoretical models and conducted experimental validation of pressure-driven insulin transport.
  • Applied physiological diastolic pressure levels to macroencapsulation membranes.
  • Integrated the pressure-enhanced system with a pump-based extravascular delivery system.
  • Tested the system's efficacy in reducing glucose levels in diabetic rodent models.

Main Results:

  • Physiological pressure increased insulin flux across membranes by nearly three orders of magnitude.
  • Pressure-driven transport enabled precise, subminute regulation of both bolus and basal insulin delivery.
  • The system rapidly reduced glucose levels in diabetic rodent models, mimicking therapeutic insulin effects.

Conclusions:

  • Applying physiological pressure is a viable strategy to enhance insulin transport in macroencapsulation systems.
  • This pressure-enhanced approach overcomes diffusion limitations, enabling on-demand insulin delivery and glucose regulation.
  • The findings suggest a promising new direction for achieving insulin independence with islet macroencapsulation for type 1 diabetes.