Deranged alpha-adrenergic regulation of growth hormone secretion in poorly controlled diabetes: reversal of the exaggerated response to clonidine after continuous subcutaneous insulin infusion.
Elevated plasma growth hormone (GH) and peripheral catecholamine levels are frequently observed in poorly controlled, insulin-dependent diabetes. Since the alpha adrenergic system plays an important role in hypothalamic regulation of GH secretion, we tested the hypothesis that altered central adrenergic activity contributes to the increased GH concentrations in diabetes. Clonidine, an alpha-adrenergic agonist, was administered to nine poorly controlled, young diabetic patients (age 12-19 yr) before and after 1 wk of continuous subcutaneous insulin infusion pump therapy. As expected, continuous subcutaneous insulin infusion lowered mean 24-h plasma glucose (from 203 +/- 21 to 112 +/- 7 mg/dl, p less than 0.01) and GH (from 17.7 +/- 2.1 to 9.2 +/- 1.2 ng/ml, p less than 0.01) to values observed in normal controls. In the diabetic patients during conventional treatment, both the peak plasma GH level postclonidine (48.3 +/- 8.7 ng/ml) and the incremental area under the GH response curve (3.23 +/- 0.58 mg X min/ml) were significantly increased above normal control values (25.2 +/- 2.1 ng/ml, p less than 0.05 and 1.63 +/- 0.11 mg X min/ml, p less than 0.0025, respectively). In contrast, the GH response to clonidine was indistinguishable from normal after only 1 wk of intensified insulin treatment. Our findings support the contention that metabolic control of diabetes influences hypothalamic regulation of GH secretion and suggests that such alterations are related, at least in part, to changes in central alpha-adrenergic activity.
Topper
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Gertner
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J
Amiel
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Press
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Genel
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Tamborlane
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WV
D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects* / Q000503:physiopathology; D007332:Insulin Infusion Systems; D008297:Male; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
D001786:Blood Glucose; D011942:Receptors, Adrenergic, alpha; D013006:Growth Hormone; D003000:Clonidine