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Related Concept Videos

Insulin Formulations: Types and Delivery01:27

Insulin Formulations: Types and Delivery

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.
Short-acting insulins are divided into rapid-acting...
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.
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment primarily uses...
Insulin: Dosing Regimen and Adverse Effects01:16

Insulin: Dosing Regimen and Adverse Effects

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.
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...
Production of Pharmaceuticals01:30

Production of Pharmaceuticals

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 sterile, tightly...
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

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 this inhibition is released...
Insulin Secretory Vesicles01:05

Insulin Secretory Vesicles

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 Injection and Hemolymph Extraction to Measure Insulin Sensitivity in Adult Drosophila melanogaster
05:52

Insulin Injection and Hemolymph Extraction to Measure Insulin Sensitivity in Adult Drosophila melanogaster

Published on: June 30, 2011

Inhaled insulin--does it become reality?

R Siekmeier1, G Scheuch

  • 1Federal Institute for Drugs and Medical Devices (BfArM), Bonn, Germany. r.siekmeier@bfarm.de

Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society
|February 17, 2009
PubMed
Summary
This summary is machine-generated.

Inhaled insulin (Exubera) failed market acceptance due to safety concerns and dosing inaccuracies. Long-term lung health effects, particularly in smokers, raise significant questions about this pulmonary drug delivery method.

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Area of Science:

  • Pulmonary Drug Delivery
  • Diabetes Management
  • Pharmacology

Background:

  • The first pulmonary-delivered insulin, Exubera, was approved in 2006 but withdrawn in 2007 due to poor market acceptance.
  • Alternative insulin delivery methods beyond injection have been explored since 1924, with lung delivery considered promising due to its absorption characteristics.
  • Concerns regarding long-term lung health effects, including potential links to bronchial tumors in smokers, emerged despite initial assumptions of minimized risks.

Purpose of the Study:

  • To review the historical development and challenges of inhaled insulin therapy.
  • To analyze the reasons behind the market withdrawal of Exubera.
  • To discuss potential future directions for pulmonary insulin delivery.

Main Methods:

  • Review of historical data and market performance of Exubera.
  • Analysis of pharmacokinetic and pharmacodynamic data of inhaled insulin.
  • Examination of reported side effects and limitations of the Exubera device.

Main Results:

  • Exubera, the most advanced inhaled insulin system, was withdrawn due to market failure.
  • Pharmacokinetics and pharmacodynamics were similar to short-acting subcutaneous insulin, but side effects included cough and shortness of breath.
  • Significant limitations included imprecise dosing capabilities and a large inhaler device, hindering accurate glycemic control.

Conclusions:

  • Inhaled insulin delivery faces significant hurdles, including safety concerns and practical limitations.
  • The increased bronchial tumor rate observed in smokers using inhaled insulin warrants caution.
  • Further development of inhaled insulin is uncertain, with only one company (Mannkind) still in Phase III trials.