$188

CIRCADIAN RHYTHM OF GASTRIC INHIBITORY POLYPEPTIDE (GIP) IN MAN. M.Salera, P.Giacomoni,L.Pironi,C.Ustra,M. Capel l i ,M.Migl io l i and L.Barbara. Clinica Medica I I I , University of Bologna; Laboratorio Central izzato, Pol i- c l in ico S.Orsola, Bologna, I ta ly .

I t has been suggested that GIP may have effects other than the insulinogenic one, par t i cu la r ly metabolic effects (1,2). In order to c l a r i f y the dai ly rela- t ionships among serum GIP levels, pancreatic i s l e t hormones levels and metabo- l i c parameters, the diurnal variat ions of blood glucose, t r ig lycer ides, insu- l i n , GIP and glucagon were studied for 24 h in 6 healthy subjects, consuming three meals (at 8:00 am, I:00 pm and 8:00 pm) and performing the i r usual phy- sical ac t i v i t i es . The hormones concentrations were estimated by speci f ic RIAs. Glucose and insul in showed early and short- last ing postprandial peaks, decl i - ning thereaf ter to basal levels within two hours. IRGIP rose from 246±38 to 861±92 pg/ml (mean±SEM) at 60 min a f ter breakfast (P<O.O05) and then progres- s ively declined to basal values. Thereafter, IRGIP levels remained s igni f ican- t l y elevated star t ing from lunch consumption unt i l night time: a f ter a f i r s t peak of 1517±147 pg/ml at 4:00 pm (P<O.O01), they were s t i l l increased at 8:00 pm (800±155 pg/ml, P<0.025), reached a second peak of 1240±145 pg/ml a f ter dinner (P<O.OI) and remained s ign i f i can t l y elevated t i l l 3:00 during the night (P<O.OI). Plasma glucagon (basal: 98±15 pg/ml) was inhib i ted by the meal inge- stion (67512 pg/ml two hours af ter each meal, P<O.05) and s l i gh t l y increased during the in terd igest ive period of the late afternoon and during the night. On the other hand, serum t r ig lycer ides tended to paral lel the GIP changes f o r ' most of the day, being s ign i f i can t l y elevated star t ing from lunch consumption (peak of 179±29 mg/dl, P<O.OI) t i l l late night (99±8 mg/dl at 5:00 am, P~O.OI). Conclusion: since i t is known that GIP fa i l s to exert any insul in releasing e f fec t in man at blood glucose levels below 100 mg/dl (3), our f indings of pers is t ing ly elevated IRGIP levels for most of the day suggest that GIP may have ef fects other than the insulinogenic one, being probably involved in the control of l i p i d metabolism. I) Wasada T., Mc Corkle K. et a l . : J Clin Invest 68: 1106-1107, 1981. 2) Eckel R.H.,-Fujimoto W.Y., Brunzell S.D.: Diabetes 28: 1141-1142, 1979. 3) Dupr~ J. , Ross S.A. et a l . : J Clin Metab Endocrinol--S~7: 826-828, 1973.

MECHANISMS OF RELEASE OF CHOLECYSTOKININ IN MAN, PIG, AND DOG. Per Lilja, George Greeley, James C. Thompson. Department of Surgery, The University of Texas Medical Branch, Galveston, TX 77550 USA.

Most data regarding release of cholecystokinin (CCK) have been obtained after bioassay studies. We have a radioimmunoassay that employs antibodies directed against CCK-33 and CCK-39 and has little or no cross-reactivity with gastrin. We measured basal and stimulated concentrations of plasma CCK in response to various agents in different species and we have studied the modu- lation of CCK release by various compounds. Results. Basal values of CCK were 80-140 pg/ml in the species studied. Food intake significantly stimu- lated CCK release to peak values that were 317% of basal in man, 161% in pigs, and 164% in dogs. Significant release of CCK occurred 5 min after food in man, 20 min in pigs, and 120 min after food in dogs. Intraduodenal (ID) infusion of triglycerides (corn oil, 1 g/kg-hr) stimulated CCK release within 20 min in all species to levels similar to those after food. ID infusion (15 mmol/hr) of buturic, heptanoic, caprylic, or nonanoic acid was without effect, while oleic acid induced significant release of CCK in dogs. Bombesin (I ~g/kg-hr, iv) released CCK in pigs. Pentobarbital anesthesia inhibited CCK release in response to fat, and halothane abolished it. Chloralose anes- thesia did not alter CCK release in response to fat. Conclusion. The temporal pattern of food-stimulated release of CCK varies among species, due in large

S189

part to differences in gastric emptying. IV bombesin, ID corn oil, and ID oleic acid stimulate CCK release, while ID fatty acids with chain length of less than 9 carbon atoms are without effect. Different general anesthetic agents have profoundly different effects on CCK release. Type of anesthesia must be considered in acute experiments on CCK release.

NEURAL MODULATION OF TRIGLYCERIDE-STIMULATED CHOLECYSTOKININ RELEASE IN DOGS. Per Lilja, Isidoro Wiener, George Greeley, James C. Thompson. Department of Surgery, The University of Texas Medical Branch, Galveston, Texas 77550 USA.

The role of the autonomic nervous system in the release of cholecystokinin (CCK) is not completely understood, in part due to lack of reliable assay techniques. We utilized a radioimmunoassay that employs an antibody directed against CCK-33 and CCK-39 to study cholinergic and adrenergic modulation of fat-stimulated release of CCK in dogs. Corn oil (i g/kg-hr) was infused intraduodenally (ID) and various compounds given intravenously (IV). Results. Results are given as integrated CCK release (ng-[O-60]min/ml) and expressed as mean ± SEM. ID corn oil significantly stimulated release of CCK. Insulin (0.25 U/kg-hr) enhanced corn oil-stimulated CCK release from 5.7±1.0 to 13.5±2.2 (~ <0.05). Atropine (50 pg/kg-hr) depressed CCK release from 5.7±1.0 to 0.7±1.1 (~ <0.05). Epinephrine (0.6 pg/kg-hr) and pro- pranolol (0.5 mg/kg-hr), when given in combination, abolished corn oil- stimulated CCK release, while each compound, when given alone, was without effect. Neither phentolamine (I0 pg/kg-min) nor isoproterenol (15 ~g/kg-hr) affected release of CCK. Conclusion. Indirect vagal stimulation enhanced, and cholinergic blockage depressed the stimulated release of CCK, which indicates that cholinergic mechanisms may be involved in the release of CCK. Alpha-receptor stimulation abolished the release of CCK, while alpha-receptor blockage was without effect. Stimulation or blockage of beta receptors did not affect CCK release. CCK release was not affected by simultaneous alpha- and beta-stimulation, indicating that beta-receptor stimulation interferes with the inhibitory effects of alpha-receptor stimulation.

DIURNAL VARIATION OF SERUM MOTILIN IN MAN. M.Salera,P.Giacomoni,L.Pironi,C.Ustra,M.Migliol i and L.Barbara. Clinica Medica I I I , Universi ty of Bologna, Bologna, I ta ly .

The physiologic role of mot i l in in humans is uncertain: i t is to be determi- ned whether the role of mot i l in in the alimentary t rac t is l imited to i ts mo- tor ac t i v i t y and whether mot i l in acts in the in terd igest ive state only or in the postprandial state as wel l . In order to c l a r i f y the possible relat ionships between c i rcu la t ing mot i l in and the physiologic events marking the day ( fast , meals, sleep), the diurnal var iat ion of serum moti l in (estimated by speci f ic RIA; Ab purchased by JC Brown, Vancouver, Canada) was studied in 6 healthy young men, consuming three meals (at 8:00 am, I:00 pm and 8:00 pm) and per- forming the i r usual physical ac t i v i t i es . Fasting levels of serum moti l in (mean±SEM: 101'15 pg/ml) were not influenced by the prevalently g lyc id ic breakfast and s l i gh t l y increased in the late morning (124±9 pg/ml). The lunch consumption decreased serum moti l in levels, which fe l l to 63±5 pg/ml at the second hour (P<O.02) and to 73±5 pg/ml at the th i rd hour a f ter the meal (P<O.05), returning thereaf ter to basal values jus t before dinner (99±13 pg/ ml). The ingestion of the evening meal e l i c i t ed a prolonged inh ib i t ion of se- rum moti l in which fe l l to 51±3 pg/ml (P<O.O01) and 53±7 pg/ml (P~O.O01) two and three hours af ter dinner respect ively. During the night, mot i l in f luctua- ted around basal levels, i ns ign i f i can t l y increasing up to 124±14 pg/ml at