Summary. Growth hormone injected intravenously in the rat elicited a 6-fold spike change in immunoreactive insulin with little variation in glucose. Subcutaneous administration of growth hormone for 4 days augmented by 56% the insulin-secretory response to glucose of isolated islets from hypophysectomised rats but not the response of control rat islets. When islets were cultured in the presence of growth hormone, the glucose-induced insulin release was increased by 35 % in batch incubations of islets from both normal and hypophysectomised rats and by 70-110% in perifused islets. Thus the capacity for stimulated release of insulin is limited by hypophysectomy, and growth hormone is capable of directly influencing the secretory function of the/3-cell.

Summary. The effects on islet function of addition to the culture medium of rat growth hormone was studied in 4-day cultured islets of Langerhans from normal and hypophysectomised rats. In islets from hypophysectomised rats, rates of insulin release were 34% lower than in control rat islets; rates of insulin plus proinsulin and total protein biosynthesis were also lower by 48% and 16% respectively. The rates of glucose oxidation and the islet content of cyclic AMP were unchanged in islets from hypophysectomised rats but the islet content of calmodulin was decreased by 68%. The presence of rat growth hormone during the culture period restored the secretory response of hypophysectomised rat islets to that seen in control islets cultured without growth hormone but had only a marginal effect on the rate of insulin plus proinsulin biosynthesis, and no significant effect on islet calmodulin content. Glucose oxidation was increased by the presence of growth hormone during the culture period in both control (73% increase) and hypophysectomised (38% increase) rat islets. Addition of growth hormone to the culture medium also enhanced rates of insulin release and biosynthesis in control islets by 116% and 20% respectively. It is suggested that these changes arise primarily from modification of the synthesis of specific islet proteins.Key words: Insulin release, insulin biosynthesis, growth hormone, calmodulin, cyclic AMP, islet glucose metabolism, hypophysectomy, cultured islets.Insulin secretion is subject to acute regulation by nutrients such as glucose and amino-acids and by hormones such as glucagon. In addition B-cell secretory * Present address: Department of Physiology, Vargas School of Medicine, Central University of Venezuela, Caracas, Venezuela function is influenced chronically by experimental manipulations such as starvation [1] or hypophysectomy [2][3][4][5], and in pregnancy [6]. We have shown that the impaired insulin secretory response of islets from hypophysectomised rats persists following 4-day culture of the islets and may be reversed by the addition of growth hormone to the culture medium [2]. To investigate the mechanisms involved, we have measured other parameters of islet function in normal and hypophysectomised rat islets cultured in the absence or presence of rat growth hormone. Materials and MethodsIslets were obtained by collagenase digestion [7] from the pancreases of male Wistar rats fed on regular rat diet (PRM, Dixon, Ware, Hefts, UK). Hypophysectomised rats were purchased from Charles River Laboratories and used after 4-5weeks from hypophysectomy. Islets were cultured for 4 days as described previously [2]. The culture medium was RPM1 1640 [8] containing glucose (6mmol/1), penicillin (0.1 mg/ml), streptomycin (0.1 mg/ml) and 10% (v/v) inactivated calf serum (Wellcome, Beckenham, Kent, UK) and was supplemented, where stated, with rat growth hormone 1 .ug/ml (National Institutes of Health, Bethesda, USA, lot GH-B-6); the pH was buffered at 7.4 with N-2-hydroxyethylpiperazine-N'-2-ethane sulph...

Rat islets of Langerhans were maintained for 2 days in tissue culture. Following the culture period, the insulin secretory responses of the islets on incubation in bicarbonate medium were measured. The enkephalin analogue D-ala2, MePhe4, Met(0)-ol (DAMME), 8.3 X 10(-8) mol/l, augmented insulin release stimulated by glucose (5 or 7 mmol/l) by 76% and 47% respectively; increased insulin release stimulated by alpha-ketoisocaproate (7.5 mmol/l) by 23%; and enhanced insulin release in the presence of glibenclamide (10 microgram/ml) plus glucose (3.3 mmol/l) by 38%. Insulin release in the presence of glucose at 2 or 12 mmol/l was not affected by DAMME (8.3 X 10(-8) mol/l). The potentiatory effect of DAMME on insulin release in the presence of glucose (5 mmol/l) was blocked by naloxone (11 mumol/l): naloxone alone did not affect glucose-stimulated insulin release. A high concentration (3.3 X 10(-6) mol/l) of DAMME did not modify glucose-stimulated insulin release. Inhibition of glucose-stimulated insulin release by trifluoperazine, an inhibitor of calmodulin, was not overcome by DAMME. Insulin secretory responses were not enhanced by exposure of the islets to DAMME (8.3 X 10(-8) mol/l) during the culture period. It is concluded that insulin release from isolated islets is capable of being influenced by an opioid peptide.

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