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Peptide YY concentrations increased in the dumping syndrome are suppressed by somatostatin
320 CHANGES
IN P L A S M A
PYY C O N C E N T R A T I O N S
IN G A S T R O I N T E S T I N A L
DISEASES
A D R I A N TE, S A V A G E AJ, B A C A R E S E - H A M I L T O N AJ, W O L F E K, B E S T E R M A N HS a n d BLOOM SR, D e p a r t m e n t of Medicine, Royal P o s t g r a d u a t e M e d i c a l School, Du C a n e Road, L o n d o n W12 OHS
P e p t i d e YY (PYY) is a n e w l y d i s c o v e r e d r e g u l a t o r y e n d o c r i n e cells of the ileal and colonic mucosa. e f f e c t s on gastric s e c r e t i o n and g a s t r o i n t e s t i n a l
p e p t i d e localised to PYY has potent inhibitory m o t o r activity.
P l a s m a c o n c e n t r a t i o n s of this new h o r m o n a l p e p t i d e were m e a s u r e d before d u r i n g a s t a n d a r d test b r e a k f a s t in several groups of p a t i e n t s with g a s t r o i n t e s t i n a l d i s e a s e s and in age m a t c h e d h e a l t h y controls.
and
Basal PYY levels were grossly e l e v a t e d (79 • 8 pmol/l) in p a t i e n t s w i t h s t e a t o r r h o e a due to small intestinal m u c o s a l a t r o p h y (tropical sprue) c o m p a r e d to c o n t r o l s 8.5 ± 0.8. P a t i e n t s with s t e a t o r r h o e a due to c h r o n i c d e s t r u c t i v e p a n c r e a t i t i s also had s u b s t a n t i a l l y i n c r e a s e d levels (49.5 ± 6.3); f u r t h e r their p o s t p r a n d i a l response was greater than that of normal subjects. M o d e r a t e e l e v a t i o n s of p l a s m a PYY w e r e also seen in patients with i n f l a m m a t o r y bowel disease and acute infective diarrhoea. In c o n t r a s t p a t i e n t s with d u o d e n a l ulcer, d i v e r t i c u l a r disease and functional bowel disease had normal PYY responses. These changes in PYY release, which appear to result from m a l a b s o r p t i o n , be involved in the bowel's a d a p t a t i o n to common d i g e s t i v e disorders.
P E P T I D E YY C O N C E N T R A T I O N S I N C R E A S E D ARE S U P P R E S S E D BY S O M A T O S T A T I N
IN THE D U M P I N G
A D R I A N TE, LONG RG, F U E S S L HS & BLOOM SR Dept. of M e d i c i n e & H i s t o c h e m i s t r y , Royal School, Du C a n e Road, London., W12 OHS
may
SYNDROME
Postgraduate
Medical
The d u m p i n g s y n d r o m e is a c o m p l i c a t i o n of gastric surgery c h a r a c t e r i s e d by sweating, faintness, a b d o m i n a l d i s t e n s i o n and d i a r r h o e a after food. The s y m p t o m s are p r o b a b l y caused by rapid transit of h y p e r o s m o l a r food w h i c h results in fluid loss into the intestinal lumen and h a e m o c o n c e n t r a t i o n . P e p t i d e YY (PYY) is a newly d i s c o v e r e d r e g u l a t o r y p e p t i d e l o c a l i s e d to e n d o r c i n e cells of the ileum and colon. In v i e w of the d i s t r i b u t i o n of PYY in the gut its response to a glucose load (50 or 100g), s u f f i c i e n t to p r o d u c e symptoms, was s t u d i e d in 6 patients. On a s e p a r a t e day the p a t i e n t s w e r e r e - s t u d i e d d u r i n g i n f u s i o n of s o m a t o s t a t i n (70 p m o l / k g / m i n ) . In h e a l t h y control subjects p l a s m a PYY levels showed little change after oral glucose. In c o n t r a s t P Y Y in dumpers rose from a basal of 12 • 3 p m o l / l to a peak of 77 ± 8 p m o l / l (p<0.001) at 60 mins. Somatostatin abolished this r e s p o n s e to glucose and s i g n i f i c a n t l y r e d u c e d basal PYY levels to 7 • 2 pmol/l. The PYY r e s p o n s e to glucose is g r e a t l y i n c r e a s e d in the d u m p i n g syndrome, p r e s u m a b l y r e f l e c t i n g the rapid p a s s a g e of h y p e r o s m o l a r fluid through the gut. PYY h a s been shown to have i n h i b i t o r y effects on gastric s e c r e t o r y and m o t o r f u n c t i o n s and m a y be i n v o l v e d in the p a t h o p h y s i o l o g i c a l c h a n g e s a s s o c i a t e d w i t h the syndrome. T h e findings also suggest that PYY release m a y be m o d u l a t e d by somatostatin.
IN P L A S M A
PYY C O N C E N T R A T I O N S
IN G A S T R O I N T E S T I N A L
DISEASES
A D R I A N TE, S A V A G E AJ, B A C A R E S E - H A M I L T O N AJ, W O L F E K, B E S T E R M A N HS a n d BLOOM SR, D e p a r t m e n t of Medicine, Royal P o s t g r a d u a t e M e d i c a l School, Du C a n e Road, L o n d o n W12 OHS
P e p t i d e YY (PYY) is a n e w l y d i s c o v e r e d r e g u l a t o r y e n d o c r i n e cells of the ileal and colonic mucosa. e f f e c t s on gastric s e c r e t i o n and g a s t r o i n t e s t i n a l
p e p t i d e localised to PYY has potent inhibitory m o t o r activity.
P l a s m a c o n c e n t r a t i o n s of this new h o r m o n a l p e p t i d e were m e a s u r e d before d u r i n g a s t a n d a r d test b r e a k f a s t in several groups of p a t i e n t s with g a s t r o i n t e s t i n a l d i s e a s e s and in age m a t c h e d h e a l t h y controls.
and
Basal PYY levels were grossly e l e v a t e d (79 • 8 pmol/l) in p a t i e n t s w i t h s t e a t o r r h o e a due to small intestinal m u c o s a l a t r o p h y (tropical sprue) c o m p a r e d to c o n t r o l s 8.5 ± 0.8. P a t i e n t s with s t e a t o r r h o e a due to c h r o n i c d e s t r u c t i v e p a n c r e a t i t i s also had s u b s t a n t i a l l y i n c r e a s e d levels (49.5 ± 6.3); f u r t h e r their p o s t p r a n d i a l response was greater than that of normal subjects. M o d e r a t e e l e v a t i o n s of p l a s m a PYY w e r e also seen in patients with i n f l a m m a t o r y bowel disease and acute infective diarrhoea. In c o n t r a s t p a t i e n t s with d u o d e n a l ulcer, d i v e r t i c u l a r disease and functional bowel disease had normal PYY responses. These changes in PYY release, which appear to result from m a l a b s o r p t i o n , be involved in the bowel's a d a p t a t i o n to common d i g e s t i v e disorders.
P E P T I D E YY C O N C E N T R A T I O N S I N C R E A S E D ARE S U P P R E S S E D BY S O M A T O S T A T I N
IN THE D U M P I N G
A D R I A N TE, LONG RG, F U E S S L HS & BLOOM SR Dept. of M e d i c i n e & H i s t o c h e m i s t r y , Royal School, Du C a n e Road, London., W12 OHS
may
SYNDROME
Postgraduate
Medical
The d u m p i n g s y n d r o m e is a c o m p l i c a t i o n of gastric surgery c h a r a c t e r i s e d by sweating, faintness, a b d o m i n a l d i s t e n s i o n and d i a r r h o e a after food. The s y m p t o m s are p r o b a b l y caused by rapid transit of h y p e r o s m o l a r food w h i c h results in fluid loss into the intestinal lumen and h a e m o c o n c e n t r a t i o n . P e p t i d e YY (PYY) is a newly d i s c o v e r e d r e g u l a t o r y p e p t i d e l o c a l i s e d to e n d o r c i n e cells of the ileum and colon. In v i e w of the d i s t r i b u t i o n of PYY in the gut its response to a glucose load (50 or 100g), s u f f i c i e n t to p r o d u c e symptoms, was s t u d i e d in 6 patients. On a s e p a r a t e day the p a t i e n t s w e r e r e - s t u d i e d d u r i n g i n f u s i o n of s o m a t o s t a t i n (70 p m o l / k g / m i n ) . In h e a l t h y control subjects p l a s m a PYY levels showed little change after oral glucose. In c o n t r a s t P Y Y in dumpers rose from a basal of 12 • 3 p m o l / l to a peak of 77 ± 8 p m o l / l (p<0.001) at 60 mins. Somatostatin abolished this r e s p o n s e to glucose and s i g n i f i c a n t l y r e d u c e d basal PYY levels to 7 • 2 pmol/l. The PYY r e s p o n s e to glucose is g r e a t l y i n c r e a s e d in the d u m p i n g syndrome, p r e s u m a b l y r e f l e c t i n g the rapid p a s s a g e of h y p e r o s m o l a r fluid through the gut. PYY h a s been shown to have i n h i b i t o r y effects on gastric s e c r e t o r y and m o t o r f u n c t i o n s and m a y be i n v o l v e d in the p a t h o p h y s i o l o g i c a l c h a n g e s a s s o c i a t e d w i t h the syndrome. T h e findings also suggest that PYY release m a y be m o d u l a t e d by somatostatin.