title: Altered cAMP response after isoprenaline stimulation of mononuclear leucocytes from insulin-dependent diabetic patients with hypoglycaemia unawareness.
abstract: Loss of adrenergic hypoglycaemic symptoms is the most distinctive feature in insulin-dependent diabetes mellitus (IDDM) patients with hypoglycaemia unawareness. Previous reports from in vivo studies show reduced heart rate responsiveness both to adrenergic agonists and antagonists in these patients. This study was carried out to investigate whether the reduced adrenergic sensitivity in IDDM patients with hypoglycaemia unawareness (IDDM-unaware) also could be demonstrated as reduced increase in cAMP production in mononuclear leucocytes induced by isoprenaline stimulation, or reduced inhibition by ICI-118551 (a selective beta 2-adrenergic receptor blocker) of isoprenaline induced cAMP production. We found that the slope of the concentration-response curves of isoprenaline/cAMP and the maximal cAMP concentrations obtained after isoprenaline stimulation were reduced in IDDM-unaware compared to control and IDDM patients with normal hypoglycaemia awareness (IDDM-aware). We did not find any significant differences in the response to ICI-118551 between control, IDDM-aware and IDDM-unaware. This study supports the reports of reduced sensitivity of adrenergic agonists as a part of the pathophysiological changes in hypoglycaemia unawareness, but we have not been able to confirm the reports of an association between hypoglycaemia unawareness and reduced effect of adrenergic antagonists.
authors.affiliation: Department of Pharmacology, University of Tromsø, Norway.
authors.forename: T S
authors.initials: TS
authors.lastname: Trovik
authors.forename: A
authors.initials: A
authors.lastname: Vaartun
authors.forename: G
authors.initials: G
authors.lastname: Sager
mesh_terms: D000318:Adrenergic beta-Agonists / Q000378:metabolism / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000494:pharmacology; D000704:Analysis of Variance; D001667:Binding, Competitive; D000242:Cyclic AMP / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000097:blood*; D007545:Isoproterenol / Q000378:metabolism / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011412:Propanolamines / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D012044:Regression Analysis; D011795:Surveys and Questionnaires
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; C026777:ICI 118551; D000242:Cyclic AMP; D007545:Isoproterenol