Interaction of amines and aminergic blocking agents with blood glucose regulation. II. α-adrenergic blockade

Abstract

The influence of α-adrenergic blockade on blood glucose homeostasis in vivo and glucose utilization in vitro was investigated in mice. The hypothesis of a dual effect of the adrenergic system on insulin-secreting mechanisms was tested. α-Adrenergic blockade by phentolamine in freely fed mice increased insulin secretion, induced hypoglycaemia and increased levels of glycogen in muscle and liver. Pretreatment with phentolamine abolished catecholamine-induced hyperglycaemia and prevented catecholamine-induced glycogenolysis in muscle and liver. Phentolamine potentiated insulin-induced hypoglycaemia in normal and alloxan-diabetic animals. Administration of catecholamines during α-blockade markedly increased plasma insulin levels. L-Noradrenaline was more potent than L-adrenaline in this respect. Pretreatment with L-propranolol abolished phentolamine-induced augmentation of insulin secretion and reduced the plasma insulin below normal levels. Adrenalectomy reduced basal plasma insulin levels. Phentolamine-induced insulin secretion was abolished in adrenalectomized and glucocorticosteroid-substituted adrenalectomized animals. α-Adrenergic blockade in vitro gave the following results on glucose utilization by muscle, liver, and adipose tissue: No effect, regarded as specific, was recorded with muscle. Total liver glycogen and 14C-incorporation into liver glycogen from labelled glucose was increased during α-adrenergic blockade in the presence of L-adrenaline and L-adrenaline+insulin. Total liver glycogen content was also augmented in the presence of phentolamine alone. Glucose utilization by adipose tissue as measured by 14CO 2-production and incorporation into 14C-lipid was increased by phentolamine alone and phentolamine in the presence of L-adrenaline+insulin; 14C-glycogen was either not affected or decreased. It is suggested that adrenaline may have a dual action on insulin secreting mechanisms analogous to its effects on the vascular system. α-Adrenergic blockade may induce a hypoglycaemic condition by (1) increased insulin secretion (2) increased glucose utilization by adipose tissue, and decreased hepatic glucose output (decreased glycogenolysis) independent of the action of insulin.