Imperial Cancer Research Fund, Histopathology Unit, 35-43 Lincoln's Inn Fields, London WC2A 3PN and. * Department of Medicine, Royal Postgraduate ...
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INSULIN AND INTESTINAL EPITHELIAL CELL PROLIFERATION. Goodlad RA, Lee CY, Gilbey S*, Ghatei MA*, Bloom SR* & Wright NA. Imperial Cancer Research Fund, Histopathology Unit, 35-43 Lincoln's Inn Fields, London WC2A 3PN & *Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, DuCane Road, London W12. The effects of modification of the levels of endogenous plasma insulin were investigated in rats fed orally and in rats fed by two types of parenteral diet. Rats were either fed a standard chow diet, or were fed by total parenteral nutrition (TPN). A high glucose 'standard' TPN diet was compared with a low glucose, reduced calorie TPN diet. In addition, a sham operated group was also studied, in which the rats were operated on, as for TPN, but then fed orally. The rats were kept on their respective treatments for seven days and were then injected with vincristine sulphate. Intestinal tissue was fixed for the determination of crypt cell production rate (CCPR) and blood was taken for hormone radioimmunoassay. Sham operation had no effect on plasma hormone levels or CCPR. The standard TPN diet was associated with significantly reduced levels of gastrin and PYY and enteroglucagon. Gastrin and PYY were further reduced by the hypocaloric diet. However, plasma insulin was very much increased in the TPN maintained group but not in the hypocaloric group. Small intestinal CCPR was reduced in the TPN groups, but no difference was observed between the standard and the low calorie TPN diets. The lack of difference in CCPR of the standard and the low-calorie TPN diets, despite the massive elevation of plasma insulin strongly suggest that insulin does not have a major role in the control of gastrointestinal epithelial cell renewal.
HUMAN PYY (3-36) INHIBITS GASTRIC ACID SECRETION (GAS) IN MAN. D . G r a n d t l , B . B u r c k h a r d t 2 , M . S c h i m i c z e k l , C . B e g l i n g e r 2 , j . R . R e e v e 3 and V . E y s s e l e i n 3 , U n i v e r s i t y H o s p i t a l s , D - 4 3 0 0 E s s e n , F R G 1 & CH-4031 B a s e l , S w i t z e r l a n d 2 and CURE & Harbor UCLA,Los A n g e l e s , U S A 3 . PYY r e c e p t o r subtypes (YI and Y2) have been described, but the i m p o r t a n c e of receptor h e t e r o g e n e i t y remains unclear. PYY(I-36) binds e q u a l l y to both subtypes.On the other hand both P Y Y ( l - 3 6 ) a n d a long C - t e r m i n a l fragment of P Y Y , P Y Y ( 3 - 3 6 ) , a r e p r e s e n t in the gut and the p e r i p h e r a l blood in man. PYY(3-36) binds to Y2 r e c e p t o r s on splenic m e m b r a n e preparations, but does not bind to Y1 r e c e p t o r s on S K - N - M or HEL cells (Grandt,unpublished).Thus,PYY(3-36) is an endogenous Y2 selective ligand. To evaluate the importance of Y2 receptors for i n h i b i t i o n of GAS in man,we examined the a c t i v i t y of synthetic PYY(3-36) on GAS in comparison to PYY(I-36) in 6 h e a l t h y human m e n . M e t h o d s . G A S was m e a s u r e d on 3 days u s i n g a s u b m a x i m a l dose (i00 ugr/kg-h) of p e n t a g a s t r i n (PG) as a stimulant. On days 1+2, PYY(I-36) or PYY(3-36),at 15 and 45 p m o l / k g . h each, were g i v e n seq u e n t i a l l y after a basal p e r i o d with PG alone. On day 3, a concomitant saline infusion was given together w i t h PG (control). GAS was q u a n t i f i e d w i t h an aspiration technique. Peptides d e l i v e r e d w e r e v e r i f i e d by R I A . R e s u l t s . G A S averaged(mean±SEM) 4.3±0.6 mmol/15' in the control experiment. Both peptides induced d o s e - d e p e n d e n t inhibitions of G A S . M a x i m a l inhibition of GAS was 28% for PYY(I-36) and 51% for PYY(3-36) ( p < 0 . 0 5 , e a c h ) . C o n c l u s i Q ~ . I n man, i n h i b i t i o n of GAS by PYY p e p t i d e s seems to be mediated by Y2 r e c e p t o r s . W e suggest that PYY(3-36) may be a p h y s i o l o g i c a l mediator of PYY function.
