ALTERED CAMP RESPONSE AFTER ISOPRENALINE STIMULATION OF MONONUCLEAR LEUKOCYTES FROM INSULIN-DEPENDENT DIABETIC-PATIENTS WITH HYPOGLYCEMIA UNAWARENESS

Loss of adrenergic hypoglycaemic symptoms is the most distinctive feat ure in insulin-dependent diabetes mellitus (IDDM) patients with hypogl ycaemia unawareness. Previous reports from in vivo studies show reduce d heart rate responsiveness both to adrenergic agonists and antagonist s in these patients. This study was carried out to investigate whether the reduced adrenergic sensitivity in IDDM patients with hypoglycaemi a unawareness (IDDM-unaware) also could be demonstrated as reduced inc rease in cAMP production in mononuclear leucocytes induced by isoprena line stimulation, or reduced inhibition by ICI-118551 (a selective bet a(2)-adrenergic receptor blocker) of isoprenaline induced cAMP product ion. We found that the slope of the concentration-response curves of i soprenaline/cAMP and the maximal cAMP concentrations obtained after is oprenaline stimulation were reduced in IDDM-unaware compared to contro l and IDDM patients with normal hypoglycaemia awareness (IDDM-aware). We did not and any significant differences in the response to ICI-1185 51 between control, IDDM-aware and IDDM-unaware. This study supports t he reports of reduced sensitivity of adrenergic agonists as a part of the pathophysiological changes in hypoglycaemia unawareness, but we ha ve not been able to confirm the reports of an association between hypo glycaemia unawareness and reduced effect of adrenergic antagonists.