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Vipergic innervation in diabetic pancreas of rats
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Role of V a s o a c t i v e Intestinal P o l y p e p t i d e (VIP) in R e ~ u l a t i n ~ P i t u i t a r y Function; Y U Z U R U KATO, A K I R A SHIMATSU, NORIO MATSUSHITA, H I K A R U O H T A and H I R O 0 IMURA; (Second Medical Clinic, D e p a r t m e n t of Medicine, Kyoto U n i v e r s i t y F a c u l t y of Medicine, Kyoto, Japan) We have p r e v i o u s l y r e p o r t e d that VIP stimulates p r o l a c t i n (PRL) s e c r e t i o n in rats, acting at least in part d i r e c t l y on the pituitary. VIP was h i g h l y c o n c e n t r a t e d in the h y p o p h y s i a l portal blood and raised by s e r o t o n i n w h i c h is known to s t i m u l a t e PRL secretion, suggesting a p o s s i b l e role of rIP as PRF in PRL s e c r e t i o n in the rat. In the c l i n i c a l studies, i n t r a m u s c u l a r injection of synthetic VIP (200 ~g) r e s u l t e d in a 4- to 7-fold increase in plasma PRL levels in normal women, w h i c h was a c c o m p a n i e d by a 553±56% (mean±SE) increase in p e r i p h e r a l plasma VIP levels at 15 min after the injection. Plasma g r o w t h hormone (GH) and c o r t i s o l levels were not changed by VIP. The i n j e c t i o n of VIP raised plasma PRL in some p a t i e n t s w i t h h y p e r p r o l a c t i n e m i a and plasma GH in some p a t i e n t s with acromegaly. In an in vitro s u p e r f u s i o n system, VIP s t i m u l a t e d PRL release in a doser e l a t e d m a n n e r from d i s p e r s e d PRL p r o d u c i n g p i t u i t a r y tumor cells, and GH release from p i t u i t a r y adenoma cells o b t a i n e d from a c r o m e g a l i c patients. VIP c o n c e n t r a t i o n s in the c e r e b r o s p i n a l fluid were e l e v a t e d in some p a t i e n t s w i t h h y p e r p r o l a c t i n e m i a and acromegaly. These findings suggest that VIP plays some role in r e g u l a t i n g PRL s e c r e t i o n in man as well as in rats and may affect GH secretion from p i t u i t a r y adenoma in acromegaly.
V i p e r g i c i n n e r v a t i o n in d i a b e t i c p a n c r e a s of rats S. KISHIMOTO, G. KAJIYAMA, A. MIYOSHI, N. Y A N A I H A R A (Department of Medicine, H i r o s h i m a U n i v e r s i t y School of Medicine, 1-2-3 Kasumi, Minamiku, H i r o s h i m a 734 Japan
The changes of VIPergic innervations were studied ~Tmunocytoch~mically in diabetic pancreas of rats. (Method) Diabetes was produced in rats by injectionof streptozotocin (80mg/kg). The rats were sacrificed 6 months after the treatment. Insulin and blood sugar levels in blood taken were determined for the diagnosis of diabetes. Three micron-wax pancreas tissue fixed in Bouin's solution was stained with HE for histopat~logy. Ten.micron frozen tissue fi.~edin p-benz _oquinone was reacted withanti serum of VIP(I :100) for VIP nerves by indirect immunofluorescence. The absorption test was done for the specificity of VIP identified. Rats injected with saline were used as the control. (Results) The B-cells were atrophied and reduced in hyperglycemic (350+10,c:120+21mg/dl) and hypoinsulinemic(38+10,c:120+21)/U~ml) rats. Both e~Dcrine and endocrine pancreas were l ~ l y replaced by fibrous tissue and cell-infiltration, resulting in marked reduction of islets,parench3~nal cells and nerve gan~lions. Conozlmitently VIP nerves were also diminished to innervate e2~xzrine and endocrine pancreas. Decreased eMocrine function was confirmed by P-S test. At the levels of ~M, survived ganglionic cells were degenerated.
Reduced and diminished VIPergie innervation as well as reduction of nerve ganglions may play one of major roles in not only endocrine but e~crine dysfunction of diabetic pancreas in the rat induced by streptozotocin.
Role of V a s o a c t i v e Intestinal P o l y p e p t i d e (VIP) in R e ~ u l a t i n ~ P i t u i t a r y Function; Y U Z U R U KATO, A K I R A SHIMATSU, NORIO MATSUSHITA, H I K A R U O H T A and H I R O 0 IMURA; (Second Medical Clinic, D e p a r t m e n t of Medicine, Kyoto U n i v e r s i t y F a c u l t y of Medicine, Kyoto, Japan) We have p r e v i o u s l y r e p o r t e d that VIP stimulates p r o l a c t i n (PRL) s e c r e t i o n in rats, acting at least in part d i r e c t l y on the pituitary. VIP was h i g h l y c o n c e n t r a t e d in the h y p o p h y s i a l portal blood and raised by s e r o t o n i n w h i c h is known to s t i m u l a t e PRL secretion, suggesting a p o s s i b l e role of rIP as PRF in PRL s e c r e t i o n in the rat. In the c l i n i c a l studies, i n t r a m u s c u l a r injection of synthetic VIP (200 ~g) r e s u l t e d in a 4- to 7-fold increase in plasma PRL levels in normal women, w h i c h was a c c o m p a n i e d by a 553±56% (mean±SE) increase in p e r i p h e r a l plasma VIP levels at 15 min after the injection. Plasma g r o w t h hormone (GH) and c o r t i s o l levels were not changed by VIP. The i n j e c t i o n of VIP raised plasma PRL in some p a t i e n t s w i t h h y p e r p r o l a c t i n e m i a and plasma GH in some p a t i e n t s with acromegaly. In an in vitro s u p e r f u s i o n system, VIP s t i m u l a t e d PRL release in a doser e l a t e d m a n n e r from d i s p e r s e d PRL p r o d u c i n g p i t u i t a r y tumor cells, and GH release from p i t u i t a r y adenoma cells o b t a i n e d from a c r o m e g a l i c patients. VIP c o n c e n t r a t i o n s in the c e r e b r o s p i n a l fluid were e l e v a t e d in some p a t i e n t s w i t h h y p e r p r o l a c t i n e m i a and acromegaly. These findings suggest that VIP plays some role in r e g u l a t i n g PRL s e c r e t i o n in man as well as in rats and may affect GH secretion from p i t u i t a r y adenoma in acromegaly.
V i p e r g i c i n n e r v a t i o n in d i a b e t i c p a n c r e a s of rats S. KISHIMOTO, G. KAJIYAMA, A. MIYOSHI, N. Y A N A I H A R A (Department of Medicine, H i r o s h i m a U n i v e r s i t y School of Medicine, 1-2-3 Kasumi, Minamiku, H i r o s h i m a 734 Japan
The changes of VIPergic innervations were studied ~Tmunocytoch~mically in diabetic pancreas of rats. (Method) Diabetes was produced in rats by injectionof streptozotocin (80mg/kg). The rats were sacrificed 6 months after the treatment. Insulin and blood sugar levels in blood taken were determined for the diagnosis of diabetes. Three micron-wax pancreas tissue fixed in Bouin's solution was stained with HE for histopat~logy. Ten.micron frozen tissue fi.~edin p-benz _oquinone was reacted withanti serum of VIP(I :100) for VIP nerves by indirect immunofluorescence. The absorption test was done for the specificity of VIP identified. Rats injected with saline were used as the control. (Results) The B-cells were atrophied and reduced in hyperglycemic (350+10,c:120+21mg/dl) and hypoinsulinemic(38+10,c:120+21)/U~ml) rats. Both e~Dcrine and endocrine pancreas were l ~ l y replaced by fibrous tissue and cell-infiltration, resulting in marked reduction of islets,parench3~nal cells and nerve gan~lions. Conozlmitently VIP nerves were also diminished to innervate e2~xzrine and endocrine pancreas. Decreased eMocrine function was confirmed by P-S test. At the levels of ~M, survived ganglionic cells were degenerated.
Reduced and diminished VIPergie innervation as well as reduction of nerve ganglions may play one of major roles in not only endocrine but e~crine dysfunction of diabetic pancreas in the rat induced by streptozotocin.