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Insulin biosynthesis and secretion.

M A Permutt, D M Kipnis

    Federation Proceedings
    |June 1, 1975
    PubMed
    Summary
    This summary is machine-generated.

    A cell membrane glucoreceptor system regulates insulin secretion and synthesis. Glucose effects on insulin involve both transcriptional and posttranscriptional regulation, impacting proinsulin messenger RNA.

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    Area of Science:

    • Endocrinology
    • Molecular Biology
    • Cell Biology

    Background:

    • Insulin secretion and synthesis are critical for glucose homeostasis.
    • The role of cell membrane receptors in glucose sensing is under investigation.
    • Understanding glucose-induced insulin production mechanisms is vital for metabolic research.

    Purpose of the Study:

    • To investigate the involvement of a cell membrane glucoreceptor system in insulin secretion.
    • To elucidate the transcriptional and posttranscriptional regulation of insulin synthesis by glucose.
    • To characterize the effects of glucose on proinsulin messenger RNA (mRNA).

    Main Methods:

    • Studied insulin secretory response to glucose after fasting and refeeding.
    • Utilized RNA synthesis inhibitors to assess transcriptional control.

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  • Employed phloridzin and plant lectins to probe glucose receptor activity.
  • Analyzed glucose-stimulated insulin synthesis in isolated rat islets using actinomycin D.
  • Quantified proinsulin mRNA levels and polysome association.

    • Main Results:

    • A cell membrane glucoreceptor system appears inducible and involved in insulin secretion.
    • Refeeding with carbohydrates, but not protein or fat, restored reduced insulin secretion after fasting, blocked by RNA synthesis inhibition.
    • Phloridzin and mushroom lectin stimulated insulin secretion, suggesting receptor-mediated effects.
    • Glucose-stimulated insulin synthesis involves both transcriptional and posttranscriptional regulation.
    • Posttranscriptional effects include increased initiation of total islet and proinsulin mRNA, with proinsulin mRNA being unexpectedly large (10-11 S).

    Conclusions:

    • Evidence supports a cell membrane glucoreceptor system mediating glucose-induced insulin secretion.
    • Glucose specifically stimulates insulin synthesis via transcriptional and posttranscriptional mechanisms.
    • Proinsulin mRNA exhibits unique characteristics regarding size and polysome association, warranting further investigation.