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Related Concept Videos

Insulin: Biosynthesis, Chemistry, and Preparation01:25

Insulin: Biosynthesis, Chemistry, and Preparation

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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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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 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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Insulin: Dosing Regimen and Adverse Effects01:16

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Insulin-replacement therapy usually includes both long-acting insulin (basal) and short-acting insulin (to cater to postprandial needs). In a diverse group of type 1 diabetes patients, the average daily insulin dose is typically 0.5-0.7 units/kg body weight. However, obese patients and pubertal adolescents may need more due to insulin resistance.
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Glucagon-like Receptor Agonists01:24

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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
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Development for Probiotics Based Insulin Delivery System.

Byung Chull An1, Jusung Lee1, Hye Yeon Won1

  • 1R&D Center, Cell Biotech, Co., Ltd., 50, Aegibong-ro 409 beon-gil, Gaegok-ri, Wolgot-myeon, Gimpo-si 10003, Gyeonggi-do, Republic of Korea.

Current Issues in Molecular Biology
|March 26, 2025
PubMed
Summary
This summary is machine-generated.

Researchers engineered a novel single-chain insulin (insulin-CBT1) for diabetes mellitus (DM) treatment. This probiotic-delivered insulin shows therapeutic potential with improved characteristics and a novel oral delivery system.

Keywords:
adipocytes differentiationdiabetes mellitus (DM)glucose uptakepancreatic beta-cell proliferationsingle-chain insulin (SCI)

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Area of Science:

  • Biotechnology
  • Endocrinology
  • Microbiology

Background:

  • Probiotics demonstrate therapeutic potential for diabetes mellitus (DM).
  • Developing recombinant insulins with enhanced properties and oral delivery methods is crucial for DM management.
  • Current insulin therapies face challenges including administration and potential side effects.

Purpose of the Study:

  • To evaluate the impact of a flexible linker peptide on the characteristics of single-chain insulin (insulin-CBT1).
  • To assess the biological anti-diabetic properties of insulin-CBT1 compared to commercial insulin.
  • To develop and validate a novel oral delivery system for insulin-CBT1 using Pediococcus pentosaceus (PP).

Main Methods:

  • Characterization of insulin-CBT1's physical and structural properties, focusing on the effect of a flexible linker peptide.
  • In vitro assessment of insulin-CBT1's effects on MIN6 cell proliferation and 3T3-L1 cell differentiation and glucose uptake.
  • Development of an oral delivery system by engineering Pediococcus pentosaceus (PP) to secrete insulin-CBT1.

Main Results:

  • The flexible linker peptide significantly increased the alpha-helix content of insulin-CBT1 (19.3% to 25.6%).
  • Insulin-CBT1 demonstrated superior MIN6 cell proliferation (1.75-fold increase) compared to commercial insulin, with lower 3T3-L1 differentiation and glucose uptake rates.
  • The Pediococcus pentosaceus-based delivery system successfully secreted insulin-CBT1 into the culture medium.

Conclusions:

  • The engineered insulin-CBT1 possesses favorable structural and biological properties for diabetes treatment.
  • A novel probiotic-based oral delivery system for insulin-CBT1 was successfully developed, offering a potential alternative to traditional insulin administration.
  • This research opens new therapeutic avenues for managing diabetes mellitus through advanced biotechnology and probiotics.