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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.
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Hormones Regulating Blood Glucose01:16

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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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Sustained Administration of β-cell Mitogens to Intact Mouse Islets Ex Vivo Using Biodegradable Poly(lactic-co-glycolic acid) Microspheres
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Automatic bolus and adaptive basal algorithm for the artificial pancreatic β-cell.

Youqing Wang1, Eyal Dassau, Howard Zisser

  • 1Department of Chemical Engineering, University of California-Santa Barbara, Santa Barbara, CA 93106, USA.

Diabetes Technology & Therapeutics
|October 1, 2010
PubMed
Summary

Automatic bolus and adaptive basal (ABAB) therapy offers improved glucose regulation for type 1 diabetes by automating insulin delivery and basal adjustments. This advanced artificial pancreas system enhances safety and reduces user intervention for better diabetes management.

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Area of Science:

  • Biomedical Engineering
  • Endocrinology
  • Artificial Intelligence in Medicine

Background:

  • Current insulin pump therapy requires significant user intervention and struggles with insulin variability and unmeasured meal disturbances.
  • Open-loop systems do not fully address the dynamic nature of glucose regulation in type 1 diabetes mellitus.
  • The need for automated, adaptive insulin delivery systems is critical for improving glycemic control.

Purpose of the Study:

  • To propose and evaluate an automatic bolus and adaptive basal (ABAB) therapy for regulating glucose levels in individuals with type 1 diabetes.
  • To develop an algorithm that automatically adjusts basal insulin and administers boluses based on real-time glucose data and meal detection.
  • To assess the performance and robustness of the ABAB therapy compared to existing methods.

Main Methods:

  • An algorithm adjusts basal insulin every 30 minutes based on interstitial glucose levels and rate of change.
  • Automated boluses are suggested for detected meals or hyperglycemia, with conservative dosing based on glucose prediction and correction factors.
  • Insulin-on-board is utilized as a safety constraint to prevent overdelivery, with a follow-up check for additional bolus needs.

Main Results:

  • ABAB therapy demonstrated superior performance over optimal open-loop therapy and missed-bolus scenarios in simulations involving 100 adult subjects.
  • Control-variability grid analysis confirmed the enhanced efficacy of the ABAB therapy.
  • The system exhibited excellent robustness to a 20% increase in insulin sensitivity, with a hypoglycemia rate of only 3.3%.

Conclusions:

  • The automatic bolus and adaptive basal (ABAB) therapy is a strong candidate for the first generation of artificial pancreas systems.
  • The proposed therapy significantly reduces user dependency and improves glucose regulation.
  • ABAB therapy shows remarkable robustness against insulin sensitivity fluctuations and dosing errors, paving the way for more autonomous diabetes management.