sincalide and Nausea

Healthy aging is associated with reductions in appetite and food intake--the so-called anorexia of aging, which may predispose to protein-energy malnutrition. One possible cause of the anorexia of aging is an increased satiating effect of cholecystokinin (CCK). To investigate the impact of aging on the satiating effects of CCK, 12 young and 12 older healthy subjects received 25-min iv infusions of saline (control) and CCK-8, 1 ng/kg per min or 3 ng/k per min, on 3 separate days before a test meal. Older subjects ate less than young subjects, and food intake was suppressed 21.6% by CCK-8, compared with the control day (P < 0.05). The suppression of energy intake by CCK-8 in older subjects was twice that in young subjects (32 +/- 6% vs. 16 +/- 6% SEM, P < 0.05) and was related to plasma CCK-8 concentrations, which were higher at baseline (P < 0.05) and increased more during CCK-8 infusions in older than young subjects (P < 0.01). The extent of suppression of food intake per given rise in plasma CCK-8 concentrations did not differ between the two age groups (P = 0.35). Endogenous CCK concentrations were higher at baseline in older subjects (P < 0.001) and decreased during the CCK-8 but not control infusions (P < 0.01), suggesting that CCK suppresses its own release. Plasma leptin concentrations were not affected by CCK infusion, whereas postprandial insulin concentrations were lowered and the peak postprandial glucose concentration was delayed but not affected by CCK-8 infusion. Because older people retain their sensitivity to the satiating effects of exogenous CCK and plasma endogenous CCK concentrations are higher in older people, increased CCK activity may contribute to the anorexia of aging.

Topics: Adult; Aged; Aged, 80 and over; Aging; Anorexia; Blood Glucose; Cholecystokinin; Eating; Fasting; Female; Humans; Hunger; Injections, Intravenous; Insulin; Leptin; Male; Nausea; Osmolar Concentration; Satiety Response; Sincalide

Recent studies suggest that the interaction between small intestinal nutrient stimulation and the blood glucose concentration is important in the regulation of gastric motility and appetite. The purpose of this study was to determine whether the effects of cholecystokinin octapeptide (CCK-8) on antropyloric motility and appetite are influenced by changes in the blood glucose concentration within the normal postprandial range. Seven healthy volunteers were studied on 4 separate days. A catheter incorporating a sleeve sensor was positioned across the pylorus, and the blood glucose was stabilized at either 4 mmol/l (2 days) or 8 mmol/l (2 days). After the desired blood glucose had been maintained for 90 min, an intravenous infusion of either CCK-8 (2 ng. kg(-1). min(-1)) or saline (control) was given for 60 min. Thirty minutes after the infusion began, the catheter was removed and subjects drank 400 ml of water with guar gum before being offered a buffet meal. The amount of food consumed (kcal) was quantified. The order of the studies was randomized and single-blinded. There were fewer antral waves at a blood glucose of 8 than at 4 mmol/l during the 90-min period before the infusions (P<0.05) and during the first 30 min of CCK-8 or saline infusion (P = 0.07). CCK-8 suppressed antral waves (P<0.05), stimulated isolated pyloric pressure waves (IPPWs) (P<0.01), and increased basal pyloric pressure (P<0.005) compared with control. During administration of CCK-8, basal pyloric pressure (P<0.01), but not the number of IPPWs, was greater at a blood glucose of 8 mmol/l than at 4 mmol/l. CCK-8 suppressed the energy intake at the buffet meal (P<0.01), with no significant difference between the two blood glucose concentrations. We conclude that the acute effect of exogenous CCK-8 on basal pyloric pressure, but not appetite, is modulated by physiological changes in the blood glucose concentration.

Topics: Adult; Appetite; Blood Glucose; Eating; Female; Gastrointestinal Motility; Humans; Hunger; Hyperglycemia; Male; Nausea; Pressure; Pyloric Antrum; Pylorus; Satiety Response; Sincalide; Single-Blind Method

Infusions of cholecystokinin (CCK) may exert their effects on appetite by inducing feelings of nausea or anxiety. In this double blind, placebo controlled crossover study, the impact of these effects on appetite were examined. Fifteen male subjects received a 20 min i.v. infusion of cholecystokinin octapeptide (CCK-8) (4 ng/kg/min) or saline. The infusion commenced 20 min after a soup preload and 10 min before an ad libitum test meal. Visual analogue scales of appetite and mood were measured over 3 h, and subjects were instructed to report any other sensations they experienced over this time. CCK-8 significantly reduced premeal hunger, elevated premeal anxiety, and reduced energy intake at the ad libitum test meal. Meal duration and rate of eating (kcal/min) were also significantly reduced after CCK-8. After the smaller meal with CCK-8, hunger rose quickly to a higher level than with placebo. The return of hunger was commensurate with the smaller amount of energy consumed and indicated that CCK did not exert an enduring effect on hunger suppression. A significant correlation was found between the reduction in energy intake and hunger (r = 0.75 p < 0.01), but not with anxiety (r = 0.15 not significant). Analyses were performed separately on subjects who did (n = 8), or did not (n = 7) report gastrointestinal disturbance. Energy intake was reduced by 56.6% and 44.6%, respectively. These results indicate that, although feelings of anxiety and nausea may accompany CCK infusions, they are not necessary for the effects of CCK on appetite. These data provide support for a role of CCK in satiety.

Topics: Adolescent; Adult; Anxiety; Appetite; Double-Blind Method; Eating; Energy Metabolism; Humans; Hunger; Infusions, Intravenous; Male; Middle Aged; Nausea; Sincalide; Time Factors

Total parenteral nutrition (TPN) induces biliary dilatation, sludge and formation of gallstones. Cholecystokinin (CCK) induces gallbladder (GB) contraction. During thyrotropin-releasing hormone (TRH) testing for thyroid function, we observed that patients felt a strong micturition reflex attributable to smooth muscle contraction of the bladder. The possibility of GB contraction after TRH administration was studied compared to cholecystokinin-octapeptide (CCK-OP) and/or fatty meal administration. The effect of intravenous (IV) CCK-OP, TRH and a combination of the two on GB volume was studied in normal volunteers without GB or liver disease and in patients receiving TPN for greater than 2 weeks. Subjects included six normal volunteers who received an oral fatty meal only, 18 other normal volunteers (Group A) and 18 TPN patients (Group B). Gallbladder contraction was estimated by ultrasound prior to and after administration of the fatty meal; in the other 36 subjects, GB contraction was calculated prior to and after administration of CCK-OP, TRH, or both. Results are expressed as a percentage of the GB basal volume using each subject as his or her own control. Group A and Group B were each divided into three equal subgroups receiving IV CCK-OP (A1, B1), TRH (A2, B2), or both (A3, B3).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Colic; Dietary Fats; Female; Gallbladder; Heartburn; Humans; Male; Middle Aged; Muscle Contraction; Muscle, Smooth; Nausea; Parenteral Nutrition, Total; Sincalide; Sodium Chloride; Thyrotropin-Releasing Hormone; Urination; Vomiting