Insulin and glucagon release in the isolated perfused rat pancreas was measured after stimulation with tolbutamide. The perfusion medium contained either 5.5 mM of glucose or was glucose free. During the first ten min of perfusion with tolbutamide, insulin output rose rapidly while glucagon release was signiticantly depressed After aperiod of prolonged stimulation glucagon began rising again but did not return to initial levels. Following destruction of insulin-producing Bcells by streptozotocin, tolbutamide still caused identical inhibition of glucagon secretion, as in the presence of intact islets. A signiflcant inverse relationship between insulin and glucagon output seemed to be established Yet, despite the fact that considerably higher insulin levels were kept in the presence of S.S mM glucose in the perfusate, tolbutamide effected about the same depression of glucagon quantitatively

Experimental diabetes was produced in rats by i.v. streptozotocin injection (65 mg/kg). There was a significant increase in blood glucose and serum glucagon, while there was a significant d~crease in serum insulin in diabetic animals as compared with controls. It is oe interest that the glucagon elevation in the streptozotocin-induced diabetes in animals is of comparable magnitude to that seen in the ketoacidotic state of human diabetes.

In order to evaluate the protective efficacy of an agonist of luteinizing hormone releasing hormone (LHRHA) on spermatogenic stem cells, we undertook a prospective study in patients with germ cell tumors. Following orchiectomy and unilateral lymph node dissection all patients received adjuvant chemotherapy consisting of 2 courses of PVB regimen (cisplatin, vinblastine and bleomycin). Six men were treated with LHRHA (d-Ser-(TBU)6 LHRH ethylamide) before, during and after PVB chemotherapy. Eight patients without LHRHA protection served as controls, receiving the identical chemotherapy. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were within normal limits before therapy in all patients. In 6/6 protected patients, serum levels of FSH, LH and testosterone were effectively suppressed during pre-chemotherapeutic LHRHA administration. All protected patients showed elevated serum FSH levels and azoospermia after cessation of chemotherapy and LHRHA treatment due to germ and stem cell loss. Median FSH level and sperm density of the protected group normalized within 24 months after chemotherapy. In all unprotected patients elevated FSH values and azoospermia also occurred after chemotherapy. Likewise, median FSH level and sperm density normalized spontaneously in this group within 24 months after chemotherapy. Our results suggest completely reversible reproductive toxicity two years after 2 courses of adjuvant chemotherapy in all patients. Administration of LHRHA during chemotherapy seems to have no protective effects on germ cells since both groups developed reproductive toxicity. Furthermore, recovery time was identical in the protected and unprotected patients. FSH and LH could be used as diagnostic markers to assess the degree and duration of reproductive and endocrine gonadal toxicity after chemotherapy.

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Competitive "binding" of endogenous and exogenous ACTH (the latter in both labelIed and unlabelled states) to silicates (QUSO G-32 and taleum) and to a varyingly active "binding factor" present in plasma was studied under several conditions. Whereas concentrations of ACTH were irrelevant, and no "binding" was observed to 5% bovine serum albumin in 0.9% saline, quantitative relations between the amounts of sillca tes and plasma volumes, respectively, and the percentage of ACTH adsorbed to the other competitor were established. The "binding" phenomenon was also studied by means of gel flitration. Radiochromatography of ACTH_I 12S incubated in plasma on Sephadex G-200 revealed a major pealc of radioactivity located in a region with large molecular WeWtl "Binding" of ACTH was prevented by an excess of Caions and by low pH-values. Whereas the physiological significance of the "binding" phenomenon remains obscure, it may weil explain the difficulties of radioimmunological measurement of ACTH in untreated plasma.

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Pancreozymin stimulates glucagon and insulin release independently of the autonomous nervous system in the isolated perfused rat pancreas in vitro. Dynamics of secretion show primary release of insulin and secondary secretion of glucagon. Presence or absence of glucose in the perfusion medium influences this pattern inversely: ~uc~se concentrations of about 100 mg % potentiate msulin release and decrease glucagon secretion, whereas absence of glucose is accompanied by augmentation of glucagon, and depression of insulin secretion.Honn. Metab. Res. 1: 224-227 (1969) K e y -W 0 r d s: Pancreozymin -Insulin Secretion in vitro -Glucagon Secretion in vitro -Isolated Perfused Rat Pancreas Stimulation of insulin release by pancreozymin (CCK-PZ) has been repeatedly observed in vivo as weIl as in vitro (cf. Pfeif/er and Raptis, 1968). Augmentation of plasma glucagon levels following pancreozymin was found in men and dogs by Unger, Ketterer, Dupre and Eisentraut (1967); Bucha'}On, Vance, Morgan and Williams (I 968); Dupre, Olms, Unger, Waddell and Beck (I 969). On the other hand, Buchanan, Vance and Williams (1969) were unable to demonstrate any effect of pancreozymin on glucagon secretion of isolated islets of rats in vitro. Moreover, Lazarus, Voyles, Devrim, Tanese and Recant (1968) as weIl as Malaisse and Malaisse-Lagae (1968) and Turner (1969) failed to confirm in vitro effectiveness of pancreozymin on incubated pieces and islets of rat and rabbit pancreas as regards stimulation of insulin secretion. Conceming the action of pancreozymin on the exocrine pancreas, Foreli, Stahlheber, Otte and Görlich (I969) suggested a linkage with a vagus reflex mechanism initiated by the contact of bile with duodenal mucosa, resulting from cholecystokinin activity. On account of this, one might • Supported by Deutsche Forschungsgemeinschaft, Bad Godesberg.assurne effectiveness of pancreozymin on islets of Langerhans in vivo only. Experiments in dogs showed an instantaneous secretion of glucagon accompanied simultaneously by an increase of insulin. In view of the known insulinogenic action of glucagon (Samols, Marri and Marks, 1965; Turner and McIntyre, 1966; Grodsky, Bennett, Smith and Schmid, 1967, a chain reaction resulting in the successive secretion of pancreozymin -glucagon -insulin was considered by Unger, Ohneda, Valverde, Eisentraut and Exton (1968) and Marks and Samols (1968). At variance to the fmdings given above, our studies report insulinogenic and glucagonogenic activities of pancreozymin on the isolated perfused rat pancreas in vitro, too. However, an inverse sequence of secretory reactions was observed. Materials and MethodsMale 250 g Wistar-albino-rats (Fa. Thomae, Biberach) were fasted 15 hours before operation, which was carried out under anesthesia with Nembutal ®. Preparation ot the isolated pancreas was performed according to Sussman, Vaughan and Timmer (I966) Le. the pancreas was separated from all surrounding tissue. The gland was perfused with an 02/C02 saturated, blood-free 1 % albumin (bovine serum albu...

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