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A physiological solvent for crystalline insulin

W D Lougheed, U Fischer, K Perlman

    Diabetologia
    |January 1, 1981
    PubMed
    Summary
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    Physiological fluids dissolve insulin crystals rapidly due to bicarbonate content, unlike simple solutions. This finding may improve insulin delivery systems for diabetes management.

    Area of Science:

    • Biochemistry
    • Endocrinology
    • Materials Science

    Background:

    • Insulin is insoluble in water at physiological pH, posing challenges for its formulation and delivery.
    • Understanding insulin solubility is crucial for developing effective diabetes management tools.

    Purpose of the Study:

    • To quantify the dissolution rates of crystalline insulin in various physiological and non-physiological solutions.
    • To identify the key components in physiological fluids responsible for insulin dissolution.

    Main Methods:

    • Developed a dissolution assay to measure the time required for insulin crystals to dissolve in different solutions at pH 7.5 and room temperature.
    • Tested distilled water, saline, Ringer's lactate, albumin solutions, human plasma, and cell culture medium.
    • Investigated the role of pH, bicarbonate, and other components by acid titration, bicarbonate repletion, and back-titration.

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    Main Results:

    • Distilled water, saline, Ringer's lactate, and albumin solutions failed to dissolve insulin within 30 minutes.
    • Human plasma and cell culture medium dissolved insulin crystals rapidly (3-8 minutes).
    • Dissolution ability was lost upon acid titration to pH 6.30, linked to bicarbonate depletion, and restored by bicarbonate repletion.

    Conclusions:

    • Bicarbonate content is critical for the ability of physiological fluids to dissolve insulin crystals at physiological pH.
    • This understanding could lead to improved insulin formulations for portable pumping systems, preventing aggregation.