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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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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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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 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-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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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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Epigenetic Conversion as a Safe and Simple Method to Obtain Insulin-secreting Cells from Adult Skin Fibroblasts
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Human serum proinsulin.

F Melani, A H Rubenstein, D F Steiner

    The Journal of Clinical Investigation
    |March 1, 1970
    PubMed
    Summary
    This summary is machine-generated.

    Human serum contains proinsulin, a precursor to insulin. This study identifies and quantifies proinsulin in normal and obese individuals, finding it increases with glucose load but its proportion relative to insulin doesn't significantly change in obesity.

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    Area of Science:

    • Endocrinology
    • Metabolic Research
    • Biochemistry

    Background:

    • Insulin is a key hormone regulating blood glucose.
    • Proinsulin is the biosynthetic precursor to insulin.
    • Understanding proinsulin levels is crucial for metabolic health assessment.

    Purpose of the Study:

    • To identify and characterize proinsulin in human serum.
    • To quantify serum proinsulin levels in normal and obese individuals.
    • To investigate the relationship between proinsulin and insulin during glucose tolerance tests.

    Main Methods:

    • Gel filtration chromatography (Bio-Gel P-30) to separate serum components.
    • Immunoassays using insulin antisera to detect and quantify proinsulin.
    • Partial tryptic digestion to assess the structure and reactivity of serum proinsulin.

    Main Results:

    • Two fractions reactive with insulin antisera were identified: proinsulin and insulin.
    • Serum proinsulin (proinsulin-like component, PLC) showed immunological identity with human proinsulin.
    • Tryptic digestion of serum PLC yielded insulin-like products.
    • Fasting proinsulin levels in normal subjects ranged from 0.05-0.4 ng/ml (5-48% of insulin).
    • Obese patients with hyperinsulinemia had elevated fasting proinsulin and increased levels post-glucose, but the proinsulin-to-insulin ratio remained similar to normal subjects.

    Conclusions:

    • The earlier eluting fraction in human serum extracts is proinsulin.
    • Serum proinsulin levels vary in normal individuals and are elevated in obese subjects with hyperinsulinemia.
    • Hyperinsulinemia in obese subjects is not associated with an increased fraction of serum proinsulin.