Kenneth Siddle

Dissociation of the effect of adrenalin on glucose uptake from that on adenosine cyclic 3',5'-monophosphate levels and on lipolysis in rat-isolated fat cells.

Abstract The effects of the adrenergic blocking agents phenoxybenzamine, phentolamine, indoramin and propranol on adrenalin-stimulated glucose uptake, lipolysis and cyclic AMP formation have been studied in rat-isolated fat cells. The β-adrenergic blocking agent propranolol was found to inhibit adrenaline-stimulated lipolysis and cyclic AMP formation at concentrations which did not inhibit adrenalin-stimulated glucose uptake. Conversely, the α-adrenergic blocking agent phenoxybenzamine inhibited adrenalin-stimulated glucose uptake at concentrations which did not inhibit lipolysis and cyclic AMP formation. The α-adrenergic blocking agents phentolamine and indoramin did not show differential effects on adrenalin-stimulated lipolysis and glucose uptake. Phenoxybenzamine had no effect on glucose uptake stimulated by insulin, adrenocorticotropic hormone and dibutyryl cyclic AMP. It is suggested that a substantial proportion of adrenalin-stimulated glucose uptake in rat-isolated fat cells is mediated by a mechanism not involving cyclic AMP. The adrenalin receptor was apparently α in type although the lack of effects of phentolamine and indoramin were not typical of those described on other α-systems.

Possible mechanisms for the increased sensitivity to glucagon and catecholamines of chicken adipose tissue during hatching.

Abstract The lipolytic sensitivity of chicken adipocytes to glucagon increases about 10-fold over the hatching period. Experiments were conducted to determine whether this change in sensitivity was related to changes in cyclic AMP metabolism within adipocytes. The capacity of glucagon to increase adipocyte cyclic AMP content was increased in 2-day-old chicks compared to 19-day embryos. This effect was seen at all glucagon concentrations, without any marked shift in the glucagon concentration for half-maximal effect. Cyclic AMP responses to catecholamines and theophylline were also greater in chick adipocytes than in cells from embryos. Lipolysis was maximally activated when cyclic AMP was increased to only a small fraction of maximum. There was some indication that a given increase in cyclic AMP content was associated with higher rates of lipolysis in chick than in embryo adipocytes. Phosphodiesterase activity was at a minimum on the day of hatching, but levels in 2-day-old chicks were similar to those in 19-day embryos. It is concluded that the increase in lipolytic sensitivity to hormones over the hatching period is associated with an increased capacity for cyclic AMP accumulation, probably due to increased adenylate cyclase activity. There may also be an increase in the sensitivity of the lipase activation system to cyclic AMP.

The action of pancreatic hormones on the cyclic AMP content of isolated chicken hepatocytes

Abstract The hormonal control of cyclic AMP content was investigated in hepatocytes isolated by collagenase digestion from chicken liver. Glucagon (2.9 × 10 −7 M ) increased cyclic AMP content within 1 min, and the concentration continued to increase for at least 30 min. More than 90% of the total cyclic AMP measured remained within the cells during this time. Significant stimulation of glycogenolysis was obtained with a glucagon concentration (2.9 × 10 −11 M ) which had no detectable effect on cyclic AMP content. Half-maximal increases in cyclic AMP content and glucose production were produced by glucagon concentrations of approximately 10 −8 and 10 −10 M , respectively. Insulin (0.17–17 × 10 −9 M ) and avian pancreatic polypeptide (0.24–240 × 10 −9 M ) had no effect on cyclic AMP content either in the presence or absence of glucagon. Adrenaline increased cyclic AMP content, the minimum effective concentration being 5 × 10 −8 M . The cyclic AMP response to adrenaline reached a peak within 2.5 min, and the maximum increase was much less than that produced by glucagon.