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Related Experiment Videos

Tolbutamide increases hypothalamic serotonin activity in the rat.

H S Grunstein, G A Smythe, J E Bradshaw

    Diabetes
    |April 1, 1986
    PubMed
    Summary

    Sulfonylurea drug tolbutamide lowers blood glucose by increasing hypothalamic serotonin (5-HT) neuronal activity, not norepinephrine (NE) activity. This study clarifies a key mechanism for this hypoglycemic agent.

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    Area of Science:

    • Neuroendocrinology
    • Pharmacology

    Background:

    • Sulfonylureas are effective hypoglycemic agents, but their precise mechanism of action is not fully understood.
    • Hypothalamic norepinephrine (NE) is known to be involved in the central neural regulation of blood glucose levels.

    Purpose of the Study:

    • To investigate whether the sulfonylurea tolbutamide lowers serum glucose by affecting hypothalamic NE neuronal activity.
    • To compare tolbutamide's effects with those of 2-deoxyglucose-induced neuroglycopenia and chronic insulin administration.

    Main Methods:

    • Acute and chronic administration of tolbutamide.
    • Measurement of serum glucose and insulin levels.
    • Assessment of hypothalamic NE and serotonin (5-HT) neuronal activity via 5-hydroxyindoleacetic acid (5-HIAA) levels.
    • Induction of neuroglycopenia using 2-deoxyglucose.
    • Chronic insulin administration for comparison.

    Main Results:

    • Tolbutamide acutely lowered serum glucose and increased serum insulin. Chronic tolbutamide lowered glucose without affecting insulin.
    • Acute tolbutamide transiently increased hypothalamic NE activity, but chronic administration did not.
    • Tolbutamide increased hypothalamic 5-HT activity, evidenced by rising 5-HIAA levels, which was not due to neuroglycopenia.
    • 2-deoxyglucose increased NE activity but decreased 5-HT activity.
    • Chronic insulin increased NE activity but did not affect 5-HT activity.

    Conclusions:

    • Tolbutamide does not lower serum glucose through a direct effect on hypothalamic NE neuronal activity.
    • Tolbutamide specifically enhances hypothalamic 5-HT neuronal activity, suggesting a role for serotonin in its hypoglycemic effects.

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