The effect of streptozotocin on the pancreatic a cell function.

Abstract

SynopsisThe effect of a single i.v. injection of30, 50, and65mg of streptozotocin (Sz) per kg of body weight on blood glucose, plasma insulin and glucagon levels was studied in rats. Responses to glucose of these three parameters were also examined in rats one week after the administration of various doses of Sz alone, Sz with nicotinamide or with picolinamide.Nicotinamide, 500mg/kg, and picolinamide, 250 mg/kg, were given i.p. 15m in before the injection of 65mg/kg of Sz.The triphasic pattern was observed after the injection of 65mg/kg of Sz not only in blood glucose and plasma insulin but also in plasma glucagon level fluctuations, the last of which showed a similar pattern to that of blood glucose responses.Further, the initial hyperglucagonemia had a delay of2hr in onset, when treated with30 and50mg/kg of Sz, respectively. Oral glucose loading resulted in a significant increase of plasma glucagon levels in rats injected with 30 and 50mg/kg of Sz, respectively.The paradoxical rise of plasma glucagon and glucose intolerance was observed in rats given Sz with nicotinamide, and Sz with picolinamide, as well as in those given Sz alone, 65mg/kg, while there was no significant difference in insulin responses between the pretreated groups of rats and controls.These results suggest that streptozotocin, even in a nondiabetogenic dose, has effect(s) on the A cell function, and that nicotinamide and picolinamide are active in protecting B cells against the cytotoxic effect, but they do not modify the effect of Sz on the A cell function.

Protection by nicotinamide against streptozotocin-induced reduction in pancreatic TRH

“…Thyrotrophin-releasing hormone (TRH) immuno¬ reactivity and biological activity has been shown to be present throughout the gastrointestinal tract and pancreas in rats (Morley et al 1977), with the largest amount occurring in the islets of Langer¬ hans (Martino et al 1978). On the other hand, streptozotocin exerts a diabetogenic action through the selective destruction of B cells of pancreatic islets (Junod et al 1967;Kazumi et al 1979Kazumi et al , 1980b, which is prevented by combined treatment with nicotinamide (Junod et al 1969;Kazumi et al 1979;Stauffacher et al 1970). Recently, Martino et al.…”

“…On the other hand, streptozotocin exerts a diabetogenic action through the selective destruction of B cells of pancreatic islets (Junod et al 1967;Kazumi et al 1979Kazumi et al , 1980b, which is prevented by combined treatment with nicotinamide (Junod et al 1969;Kazumi et al 1979;Stauffacher et al 1970). Recently, Martino et al (1978) reported that marked decreases in TRH in whole pancreas and in isolated islets were found in rats 7-10 days after induction of streptozotocin diabetes.…”

Portal somatostatin reponds to intragastric glucose: Effects of streptozotocin diabetes.

“…Statistical comparisons between groups were made using non-paired Student's t test. (Kazumi et al, 1979) of our laboratory damonstrated that a paradoxical rise of glucagon in response to intragastric glucose administration wasfound not only in streptozotocin-diabetic rats but also in non-diabetic animals treated with nicotinamide and a diabetogenic dose of streptozotocin, suggesting that the nitrosourea compound may act directly on the A cells. The present results cannot therefore rule out the possibility of a direct effect of streptozotocin on D cells.…”

Η Επίδραση Της Άσκησης Στο Καρδιαγγειακό Σύστημα Διαβητικών Επιμύων

“…Έτσι, κατά τις πρώτες δύο ώρες έπειτα από τη χορήγηση της STZ, η ινσουλίνη πλάσματος εμφανίζεται μετρίως μειωμένη ενώ το γλυκογόνο είναι αυξημένο. Ο Junod και οι στο διαβήτη που προκαλείται από STZ 869. Τέλος, όσον αναφορά στην σωματοστατίνη, τις πρώτες ημέρες έπειτα από τη χορήγηση της STZ, τα δ κύτταρα εμφανίζονται ανεπηρέαστα και τα παγκρεατικά επίπεδα της σωματοστατίνης είναι φυσιολογικά 870.…”