Defects in insulin secretion in NIDDM: B-cell glucose insensitivity or glucose toxicity?

T. W. van Haeften*

*Corresponding author for this work

    Research output: Contribution to journalReview articleAcademicpeer-review

    5 Citations (Scopus)

    Abstract

    In NIDDM, first-phase insulin release to glucose is (almost) absent. However, in contrast to older studies which suggested that in NIDDM the B-cell is ''blind'' for glucose, recent evidence indicates that the B-cell is not insensitive for glucose as far as second phase release is concerned. This suggests that the metabolism of glucose is probably not deranged in NIDDM, since glucose leads to insulin release after it has been metabolized. Hyperglycaemia itself has a deleterious effect on insulin release, so-called glucose toxicity. Various mechanisms have been proposed, whereby hyperglycaemia may diminish insulin release: inhibition of Ca2+ mobilization from the endoplasmic reticulum by glucose-6-phosphate, Ca2+ uptake in the ER by glucose and inhibitory effects of protein kinase C. Whatever may prove to be the underlying mechanism(s), glucose toxicity is unlikely to be the only cause of insulin secretory disturbances in NIDDM, since the glucose level would have to be elevated before it could be toxic. Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by both defects in insulin action and insulin secretion. With regard to the defects in insulin release, much research has originated from two (partly) opposing hypotheses, namely the presence of pancreatic B-cell glucose blindness and the hypothesis of pancreatic B-cell glucose toxicity in NIDDM.

    Original languageEnglish
    Pages (from-to)30-35
    Number of pages6
    JournalNetherlands Journal of Medicine
    Volume42
    Issue number1-2
    Publication statusPublished - Feb-1993

    Keywords

    • NON-INSULIN-DEPENDENT DIABETES-MELLITUS
    • BETA-CELL
    • INSULIN
    • GLUCOSE TOXICITY
    • PANCREATIC BETA-CELLS
    • DOSE-RESPONSE CHARACTERISTICS
    • ISOLATED RAT ISLETS
    • PROTEIN KINASE-C
    • DIABETES-MELLITUS
    • CHRONIC HYPERGLYCEMIA
    • INTRACELLULAR CA-2+
    • GLUCAGON-SECRETION
    • ARACHIDONIC-ACID
    • RELEASE

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