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Insulin Secretory Vesicles01:05

Insulin Secretory Vesicles

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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: 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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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: 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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Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

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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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GH/IGF-I/insulin system in centenarians.

Giovanni Vitale1, Michelangela Barbieri2, Marina Kamenetskaya3

  • 1Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy; Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, Milan, Italy.

Mechanisms of Ageing and Development
|December 10, 2016
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Investigating the growth hormone/insulin-like growth factor-I (GH/IGF-I)/insulin pathway in centenarians reveals insights into successful aging. This pathway

Keywords:
AgeingCentenariansIGF-IInsulinLongevity

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Area of Science:

  • Endocrinology and aging research.

Background:

  • The endocrine system, particularly the GH/IGF-I/insulin pathway, is crucial for biological regulation and aging.
  • Evolutionary conservation and cross-species similarities suggest this pathway's role in lifespan.
  • Centenarians exemplify successful aging, delaying age-related diseases.

Purpose of the Study:

  • To review the endocrine profile of centenarians regarding the GH/IGF-I/insulin system.
  • To explore the pathway's relevance in modulating aging and longevity.

Main Methods:

  • Review of existing literature on centenarian endocrine profiles.
  • Focus on the GH/IGF-I/insulin signaling pathway.

Main Results:

  • Centenarians exhibit a distinct endocrine profile related to the GH/IGF-I/insulin system.
  • Downregulation of this pathway is hypothesized to contribute to extended lifespan and healthy aging.

Conclusions:

  • The GH/IGF-I/insulin pathway is a key modulator of aging and longevity.
  • Understanding centenarian endocrine profiles offers potential strategies for promoting healthy aging and extending human lifespan.