Terbutaline decreases the blood flow of the pancreatic islets but does not reduce the diabetogenic action of streptozotocin in the rat

Male Sprague-Dawley rats were injected i.v. with either 0.5 ml saline or terbutaline (1 mg/kg body weight) and 5 min later the whole pancreatic blood flow (PBF) and the islet blood flow (IBF) were measured with a microsphere technique. Injection of terbutaline increased the serum insulin concentrations, but had no effect on the serum glucose concentration of the animals. The IBF was decreased by terbutaline by approximately 40%, while the PBF remained unchanged. Furthermore, the diabetogenic action of streptozotocin (SZ; 35 mg/kg bodyweight; i.v.) was not affected by the administration of terbutaline 5 min before the SZ injection. It is concluded that the beta 2-selective adrenoceptor agonist terbutaline selectively decreases the blood flow of the pancreatic islets in spite of its stimulatory effects on the release of insulin. This confirms our previous findings that the IBF and the release of insulin can be dissociated. Moreover, the hyperglycemic action of a single diabetogenic dose of SZ could not be reduced by terbutaline administration despite the reduction in the IBF. This suggests that a decrease in the islet blood flow is not sufficient to prevent the cytotoxicity of SZ.     

Carbachol has opposite effects to glucose in raising the sodium content of pancreatic islets.

Integrating flame photometry was used for measuring sodium in single pancreatic islets from ob/ob mice. Exposure to 100 microM carbachol resulted in a 25-40% increase in sodium without any effect on potassium during incubation with 0-5 mM glucose in media deficient or not in Ca2+. This action of carbachol was abolished by 10 microM atropine or by raising the glucose concentration to 20 mM. A minor increase of the steady state content of sodium occurred in the presence of 200 microM ATP or 10 nM tetradecanoylphorbol 13-acetate (TPA). Carbachol differed from TPA in markedly stimulating sodium accumulation after ouabain inhibition of the Na/K pump. The results indicate that muscarinic receptor activation has opposite effects to glucose in inducing a rise of the islet content of sodium. It is suggested that the cholinergic control of the endocrine pancreas involves entry of Na+ in addition to the Na+ entry mediated by protein kinase C activation of Na+/H+ countertransport.     

Early developmental 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure decreases chick embryo heart chronotropic response to isoproterenol but not to agents affecting signals downstream of the beta-adrenergic receptor.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes cardiovascular toxicity in laboratory animals, including alteration in several processes in which beta-adrenergic receptor (beta-AR) signaling plays important roles. Thus, our laboratory investigated the effects of TCDD on beta-AR expression and signal transduction. Fertile chicken eggs were injected with vehicle (corn oil), 0.24 or 0.3 pmol TCDD/g egg on incubation day 0 (D0) or D5. On D10, heart function was assessed by ECG in ovo. Exposure to TCDD increased the incidence of arrhythmias and decreased the positive chronotropic responsiveness of the heart to isoproterenol. The reduced beta-AR responsiveness was, in part, independent of any overt morphological changes in the heart as chick embryos exposed to TCDD on D5 displayed an intermediate responsiveness to beta-AR agonist in the absence of the dilated cardiomyopathy observed in chick embryos exposed to TCDD on D0. TCDD did not decrease the chronotropic response of the heart to agents that stimulate signals downstream of the beta-AR. In fact, TCDD-exposed embryos were more sensitive than controls to forskolin, increasing heart rates (HR) 21.8 +/- 3.5 beats per min (bpm) above baseline versus control values at 6.3 +/- 2.7 bpm above baseline. TCDD exposure also augmented the negative chronotropic response of the heart to verapamil, decreasing HR -23.2 +/- 7.4 bpm relative to baseline versus control embryos at -12.7 +/- 5.9 bpm below baseline. Finally, the mean cardiac beta1-AR mRNA expression in D10 embryos was not significantly altered by exposure to TCDD on D0. These findings establish that a functional end point of the developing chick heart is sensitive to TCDD exposure and that the TCDD-induced reduction in beta-AR responsiveness may result from alterations in signal transduction upstream of adenylyl cyclase.