Decreased beta 2-adrenoceptor density and decreased isoproterenol induced c-AMP increase in juvenile type I diabetes mellitus: an additional cause of severe hypoglycaemia in childhood diabetes?
Little is known about the receptor and post receptor mechanisms of sympathoadrenal signal transmission in type I diabetes mellitus. Therefore, we examined the maximum binding of granulocyte beta 2-adrenoceptors and the in vitro c-AMP accumulation in lymphocytes of 24 children and adolescents with diabetes mellitus and 14 similarly aged healthy subjects. The number of high affinity beta 2-adrenoceptors on granulocytes correlated significantly with unstimulated (r = 0.6, P < 0.004) and with isoproterenol stimulated c-AMP values in lymphocytes (r = 0.68, P < 0.0007) showing the proportional changes of beta 2-adrenoceptors and c-AMP in two different cells. The number of beta 2-adrenoceptors on granulocytes was significantly reduced in diabetic as compared to healthy children (median 1397, range 599-3405 vs. 2205, 825-3200 beta 2-adrenoceptors per granulocyte, P = 0.014). Moreover, the percentage in vitro stimulation of c-AMP by isoproterenol in lymphocytes was significantly reduced in diabetic children as compared to healthy individuals (120%, 39%-278% vs. 225%, 66%-500%, P = 0.012). These results indicate a decreased sympathoadrenergic signal transmission in peripheral blood cells as a model for the liver probably contributing to severe hypoglycaemia in diabetic children.
Schwab
K O
KO
Department of Paediatrics, University of Würzburg, Germany.
Bartels
H
H
Martin
C
C
Leichtenschlag
E M
EM
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D000242:Cyclic AMP / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000145:classification / Q000150:complications / Q000378:metabolism*; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000150:complications / Q000503:physiopathology*; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology*; D008214:Lymphocytes / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000032:analysis*
D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; D000242:Cyclic AMP; D007545:Isoproterenol