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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: Biosynthesis, Chemistry, and Preparation01:25

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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 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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Production of Pharmaceuticals01:30

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Industrial insulin production uses genetically engineered E. coli expressing a proinsulin gene controlled by a tryptophan promoter and containing a methionine linker for later cleavage. The cells also carry ampicillin resistance for selective growth. Seed cultures are stored at −80 °C and production begins by thawing a small amount to inoculate starter cultures, which are progressively scaled to a 50,000-L bioreactor. In the bioreactor, E. coli grow in nutrient-rich media under...
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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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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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Coculture Analysis of Extracellular Protein Interactions Affecting Insulin Secretion by Pancreatic Beta Cells
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CPP mediated insulin delivery: current status and promising future.

Ergang Liu, Jianyong Sheng, Junxiao Ye

  • 1Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Rd, Shanghai 201203, P.R. China. jxwang@shmu.edu.cn.

Current Pharmaceutical Biotechnology
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Summary
This summary is machine-generated.

Cell penetrating peptides (CPPs) offer a promising strategy to enhance insulin bioavailability via non-invasive routes. This review explores CPP-based delivery systems for improved insulin transport and potential clinical applications.

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Area of Science:

  • Biomedical Engineering
  • Drug Delivery Systems
  • Pharmacology

Background:

  • Parenteral insulin administration faces challenges with intolerance and limited success of current delivery enhancement methods.
  • Cell penetrating peptides (CPPs) show potential for improving the transport efficiency of large molecules like insulin.
  • Previous studies indicate CPPs can significantly increase insulin bioavailability, particularly via nasal delivery.

Purpose of the Study:

  • To review recent advancements in cell penetrating peptide (CPP)-mediated insulin transport.
  • To outline various CPP-based strategies for insulin delivery.
  • To assess the potential for clinical translation of these CPP-mediated delivery systems.

Main Methods:

  • Review of existing literature on CPPs and insulin delivery.
  • Analysis of different CPP formulation and conjugation strategies with insulin.
  • Evaluation of reported bioavailability data for CPP-enhanced insulin delivery.

Main Results:

  • CPPs have demonstrated the ability to enhance insulin transport and bioavailability.
  • Nasal administration of insulin with CPPs achieved up to 50.7% bioavailability compared to subcutaneous injection.
  • CPPs can be formulated directly with insulin or attached to drug carriers for delivery.

Conclusions:

  • CPP-mediated insulin transport presents a viable strategy to overcome limitations of current insulin delivery methods.
  • Various CPP-based delivery approaches show promise for future clinical applications.
  • Further research into CPP-based systems could lead to improved insulin therapy.