Accuracy of resting energy expenditure calculations in unselected overweight and obese patients.

AIMS: Measurements of resting energy expenditure (REE) were compared with the data of 14 equations to determine their accuracy. METHODS: REE measurements by indirect calorimetry in 1,032 unselected overweight and obese men (n = 306) and women (n = 726) were compared with calculations by 14 different formulas. RESULTS: The mean (± SD) values calculated with the Owen, Robertson and Reid and WHO-I equations were not significantly different from our measurement of 1,682 ± 441.9 kcal/24 h. The values obtained with the Livingston, Mifflin, Müller and Bernstein equations were significantly different but still within a range of ±100 kcal/24 h. For females, the best comparison was observed with the Müller equation which, however, differed substantially in males. For men, the Cunningham equation was best, but it gave the worst comparison in women. A good individual match was only obtained with the equation of Robertson and Reid in 34% of the men and with the Owen equation in 38% of the women. All other formulas were less accurate. Drug treatment for 55% of the subjects had no effect on the mismatch between calculated and measured data. CONCLUSION: Calculations of REE with most equations seem to be valid in a group analysis but they are not helpful for the estimation of an obese patient's individual energy expenditure.

Relationship of fetuin-A levels to weight-dependent insulin resistance and type 2 diabetes mellitus.

OBJECTIVE: Weight gain and obesity are of substantial importance for the development of insulin-resistance and type-2 diabetes mellitus. Fetuin-A, a liver-derived glycoprotein, may also play a role in these alterations. Several studies have demonstrated an association between fetuin-A and body weight which, however, was within a fairly small range at the border of overweight to obesity. The present study examines the relationship between fetuin-A and a wide range of BMI, together with basal insulin, and HOMA-IR. In addition, matched groups of non-diabetic patients and those with type-2 diabetes mellitus were compared. METHODS: We examined the relationship between fetuin-A and BMI, insulin, HOMA-IR, glucose and HbA1c in a cohort of 445 non-diabetic obese subjects and 150 obese patients with type-2-diabetes mellitus (DM2). RESULTS: In relation to quintiles of fetuin-A a significant increase of BMI, basal insulin and HOMA-IR was observed between the 1st and 2nd quintile with no further change thereafter. Correspondingly, fetuin-A levels increased significantly only between the 1st and 2nd quintile of BMI, insulin or HOMA-IR, respectively. When patients with type 2 diabetes were compared with non-diabetic subjects matched for BMI, insulin, and age median fetuin-A levels were not significantly different. CONCLUSION: At the early stage of weight gain fetuin-A could be of relevance for the development of insulin resistance. For the further progressive resistance with increasing weight in the obesity range the present data do not support a role of fetuin-A. Similarly its contribution to the resistance of type-2 diabetes seems to be of minor importance.

Low-dose ghrelin infusion--evidence against a hormonal role in food intake.

Ghrelin is the only peripheral orexigenic peptide of gastrointestinal origin. Its preprandial increase is supposed to initiate food intake. This assumption is based on studies with intravenously infused ghrelin in rather high doses and the correlation between ghrelin levels and hunger sensations. As yet it is unclear whether or not low dose ghrelin resulting in physiological and moderately supraphysiological plasma levels has an effect on hunger sensations, the wish for food intake and / or the quantity of the meal consumed. We examined 20 normal-weight males (age 25±1.7 years, BMI 24±0.5 kg/m(2)) in a prospective double-blind randomized fashion. On two different days they obtained a ghrelin infusion 1 ng/kg/min or intravenous saline starting one hour after a standardized meal. Hunger and satiety ratings were documented by visual analogue scales. A second meal was served on demand and consumed until feeling satiated. Time point of the second meal as well as ingested calories were registered. Prior to the start of i.v. ghrelin the postprandial decrease of active plasma ghrelin by 30 pg/ml was comparable. In the controls the postprandial reduction was significant until 210 min compared to basal. With i.v. ghrelin basal levels were reached within 10 min. The maximal rise was twice basal. No effect was observed on hunger and satiety ratings. The time period between the meals and the food quantity of the second meal were similar. During ghrelin infusion glucose and growth hormone but not insulin and cortisol levels were significantly higher after the second meal compared to saline. The present data demonstrate for the first time the effect of a low dose ghrelin infusion on food intake. Neither physiological nor moderably supraphysiological ghrelin levels were associated with any change of the various food intake parameters determined. These data do not favour a hormonal role of peripheral ghrelin in the regulation of food intake.

Impact of breakfast on daily energy intake--an analysis of absolute versus relative breakfast calories.

OBJECTIVE: The role of breakfast energy in total daily energy intake is a matter of debate. Acute feeding experiments demonstrated that high breakfast energy leads to greater overall intake supported by cross-sectional data of a free-living population. On the other hand, a large intraindividual analysis has indicated that a high proportion of breakfast to overall intake is associated with lower daily energy intake. To evaluate these apparently contradictory results in greater detail both ways of analysis were applied to the same data set of dietary records. METHODS: On an intraindividual basis total daily energy intake was related to the absolute values of breakfast energy intake or to the ratio of breakfast to overall intake, respectively. Food intake of 280 obese and 100 normal weight subjects was analyzed who recorded over 10 (obese) or 14 (normal weight) consecutive days, respectively. RESULTS: Increasing breakfast energy was associated with greater overall intake in normal weight and obese subjects. The increasing ratio of breakfast to total daily energy intake was associated with a significant reduction of overall intake on days where post-breakfast energy was significantly reduced. Correlational and multiple regression analysis support the concept that absolute breakfast calories have the strongest influence on daily energy intake. CONCLUSION: Reduced breakfast energy intake is associated with lower total daily intake. The influence of the ratio of breakfast to overall energy intake largely depends on the post-breakfast rather than breakfast intake pattern. Therefore, overweight and obese subjects should consider the reduction of breakfast calories as a simple option to improve their daily energy balance.

Successful weight loss and maintenance in everyday clinical practice with an individually tailored change of eating habits on the basis of food energy density.

BACKGROUND: Weight change was analyzed in a cohort of obese patients whose eating habits were changed individually mainly on the basis of food energy density (ED) to evaluate the feasibility of this concept for a larger controlled trial. METHOD: Five hundred and thirteen outpatients were treated between January 2003 and December 2006. Dietary counseling was based on a pretreatment food diary. In January 2008, a follow-up (FU) was made. For pre- and post-change eating habits, 5184 dietary protocols of 189 patients were analyzed. RESULTS: During 10.5 months of treatment, patients lost weight from an initial BMI of 38.8 ± 8.5 by -0.195 kg/m(2) per month; 36% had weight loss >5%, 44% lost 0-4.9% and 20% had weight gain. At follow-up, 413 patients (80.5%) were reached of whom 80 were still in treatment while 333 were considered as self-treatment (ST) group. The ST group had further weight loss by -0.053 kg/m(2) per month over 16.8 months (40% weight loss, 46% maintenance and 14% weight gain), and 164 patients with type-2-diabetes had greater weight loss compared to those without diabetes during ST (Δ-BMI-0.166 vs. -0.028 points/month; p < 0.0001). Energy intake (EI) was reduced by lower ED, beverages and number of meals. Average carbohydrate, fat and protein intake was reduced by 28, 42, and 7%, respectively. CONCLUSION: In a unselected cohort of substantially obese patients, the individual change of eating habits based primarily on food ED in conjunction with beverage intake and meal frequency weight loss continued beyond the supported treatment phase indicating a good patient adherence. We consider these data as an encouraging pilot study that certainly requires confirmation under controlled conditions.

Contribution of energy density and food quantity to short-term fluctuations of energy intake in normal weight and obese subjects.

BACKGROUND: In normal weight subjects it is known that day-to-day energy intake (EI) can vary substantially while this question has not been examined in obese subjects. From acute feeding experiments one would assume that these perturbations are mainly due to differences in food energy density (ED). However, food quantity (FQ) during single meals, number of meals, cognitive and sensory mechanisms may also contribute to the modification of EI. OBJECTIVE AND DESIGN: To obtain more detailed information about day-to-day variations of food intake food diaries recorded during 10 consecutive days of 280 obese and 100 normal weight subjects were examined. RESULTS: The chronological analysis shows a fairly constant pattern for EI, FQ and ED in both groups. The group analysis, however, masks individual fluctuations since the coefficients of variation were between 20 and 24% for the three parameters, respectively. This corresponds to a range of 1,200 kcal. Sixty-five percent can be accounted for changes in FQ and 35% as the result of variations in ED. Snacks between main meals account for 20% of daily EI but only 10% of FQ. Furthermore, snack EI is not compensated during main meals. CONCLUSION: Small day-to-day changes of EI are due to increased meal quantities while greater fluctuations are also due to higher food ED. The present data suggest that modification of FQ by cognitive and sensory factors plays an important role in the variation of daily EI under real life conditions with no major difference between normal weight and obese subjects.

Weight-dependent differential contribution of insulin secretion and clearance to hyperinsulinemia of obesity.

Obesity is associated with insulin resistance and the resulting hyperinsulinemia has been attributed to an increase of insulin secretion and a reduction of insulin clearance. The present study was intended to further characterize the relative contribution of secretion and clearance especially in the postprandial state. In relation to WHO body weight classes 291 subjects were divided in 5 subgroups Basal insulin concentrations rose stepwise and significantly with increasing BMI. This was paralleled by C-peptide concentrations and insulin secretion, while the reduction of insulin clearance was less stringent in relation to BMI. Basal glucose was unchanged in the BMI25 group and 8% higher in the obese groups (BMI 30, 35, 40) compared to normal weight (NW). Although postprandial insulin concentrations were significantly higher in the overweight and obese groups compared to NW the correlation was not as tight as in the basal state. Furthermore, the present data demonstrate for the first time that insulin secretion only increased in the overweight group without further augmentation in the obese groups. Further hyperinsulinemia of the latter was due to weight-dependent reduction of insulin clearance. The postprandial glucose response was 38-82% higher with increasing weight compared to NW. In summary basal hyperinsulinemia is mainly due to weight related increase of insulin secretion with moderate contribution of reduced insulin clearance. Postprandially, hyperinsulinemia of overweight is predominantly due to secretion while further postprandial hyperinsulinemia of obese subjects is mainly due to reduced clearance. Thus, postprandial insulin secretion cannot respond adequately to the challenge of weight-dependent insulin resistance already in non-diabetic obese subjects.

Differential inhibition of galanin- and ghrelin-induced food intake by i.c.v. GLP-1(7-36)-amide.

Feeding regulation involves both anorectic and orexigenic neuropeptides mainly located in the hypothalamus. To gain further insight into the interaction between these two groups of regulators inhibition of feeding induced by glucagon-like peptide-1 (GLP-1) was examined during stimulation of food intake by equimolar doses of ghrelin and galanin. The experiments were carried out in freely feeding rats. Intracerebroventricular (i.c.v.) injections were accomplished through stereotaxically implanted cannulae aimed at the lateral cerebral ventricle. Food intake of standard rat chow pellets was subsequently recorded for 2 h. Ghrelin and galanin stimulated food intake significantly with no difference between these two peptides. During ghrelin stimulation GLP-1 inhibited feeding in doses between 0.015 and 1.5 nmol. During galanin stimulation of food intake a ten fold higher dose (0.15 nmol) was required to inhibit food intake. In conclusion equimolar doses of i.c.v. ghrelin and galanin are similarly effective stimuli of food intake when given alone. However in combination with an anorectic neuropeptide such as GLP-1 they have substantially different potencies of feeding stimulation. Such interaction could also be of interest for therapeutic strategies involving both regulating groups of neuropeptides.

Development of hyperinsulinemia and insulin resistance during the early stage of weight gain.

Obesity is associated with insulin resistance and hyperinsulinemia, which is considered to be a core component in the pathophysiology of obesity-related comorbidities. As yet it is unknown whether insulin resistance and hyperinsulinemia already develop during weight gain within the normal range. In 10 healthy male subjects the effect of intentional weight gain by 2 BMI points was examined on insulin. C-peptide and glucose levels following a meal, 75 g of glucose, and a two-step hyperglycemic clamp increased plasma glucose by 1.38 and 2.75 mmol/l, respectively. Baseline insulin, C-peptide, and glucose concentrations were significantly higher after weight gain from 21.8 to 23.8 kg/m(2) BMI within 4(1/2) mo. Calculations of insulin secretion and clearance indicate that reduced insulin clearance contributes more to post-weight gain basal hyperinsulinemia than insulin secretion. Following oral or intravenous stimulation insulin concentrations were significantly higher post-weight gain during all three test conditions, whereas C-peptide and glucose levels did not differ. Calculations of insulin secretion and clearance demonstrated that higher stimulated insulin concentrations are entirely due to clearance but not secretion. Despite significantly higher insulin levels, the rate of intravenous glucose required to maintain the defined elevation of glucose levels was either identical (1.38 mmol/l) or even significantly lower (2.75 mmol/l) following weight gain. The present study demonstrates for the first time that insulin resistance already develops during weight gain within the normal range of body weight. The associated basal and stimulated hyperinsulinemia is the result of differentiated changes of insulin secretion and clearance, respectively.

Interacción entre leptina y grelina como parte del control tónico de la ingesta de alimentos / Interaction between leptin and ghrelin as part of tonic control of food intake

Food intake is regulated by an acute control system that conveys information between the stomach and hypothalamic centres of feeding regulation mainly via neural vagal afferent fibers for satiety and via hormonal signal transmission by ghrelin for recurrence of appetite and hunger. This acute system is under tonic control by adipocyte-derived leptin as an indicator of the nutritional status of the organism. In obese subjects plasma leptin is higher compared to normal weight subjects (NW). This is associated with lower ghrelin levels suggesting that the negative feedback loop to reduce food intake in the case of sufficient energy reserves is intact. A differential analysis of the inverse relationship between leptin and ghrelin, however, suggests an inhibitory effect of leptin is restricted to male normal and overweight subjects. In females and obese subjects of both genders this inverse relationship does exist. These findings indicate that the position of ghrelin within the control system of food intake is somewhat more sophisticated than previously thought and it requires more detailed analysis

La ingesta de alimentos está regulada por un sistema de control inmediato que transmite información entre el estómago y los centros hipotalámicos de regulación de la alimentación, principalmente a través de fibras aferentes vagales nerviosas para la saciedad y mediante la transmisión de señales hormonales de la grelina para la recurrencia del apetito y el hambre. Este sistema inmediato se encuentra bajo control tónico de la leptina derivada de los adipocitos como indicador del estado nutricional del organismo. En los individuos obesos la leptina plasmática es más alta en comparación con los individuos de peso normal. Esto se asocia con concentraciones más bajas de grelina, lo que sugiere que el asa de retroalimentación negativa para reducir la ingesta de alimento en el caso de reservas suficientes de energía está intacta. Sin embargo, el diagnóstico diferencial de la relación inversa entre leptina y grelina sugiere que el efecto inhibidor de la leptina está restringido a hombres normales y con sobrepeso. En las mujeres y en los individuos obesos de ambos sexos existe esta relación inversa. Estos hallazgos indican que la posición de la grelina dentro del sistema de control de la ingesta de alimentos es algo más sofisticada de lo que antes se creía y requiere un análisis más detallado

Plasma ghrelin levels during exercise - effects of intensity and duration.

Ghrelin, a recently discovered hormone of gastric origin has been shown to stimulate appetite and food intake. In man it is considered to play a role in energy homeostasis and regulation of somatropic function. As exercise affects hunger/satiety sensations and food intake, at least under some experimental conditions, we investigated the effect of exercise intensity and duration on ghrelin release and subsequent ad libitum food intake in normal weight subjects. Bicycle exercise on an ergometer for 30 min at 50 W which was below the aerob-anaerobic threshold led to an increase of ghrelin which remained unchanged during the higher intensity at 100 W. Respective hunger/satiety ratings and subsequent food intake and postprandial ghrelin suppression were identical and not different from controls. In a second group 7 subjects cycled at 50 W for 30, 60 and 120 min, respectively. Ghrelin concentrations rose significantly by 50-70 pg/ml above baseline for the respective period of exercise. While postexercise premeal ghrelin levels were not significantly different subsequent food intake after 120 min of cycling was significantly greater compared to control, 30 min and 60 min exercise, respectively. The present data suggest that low rather than high-intensity exercise stimulates ghrelin levels independent of exercise duration. Stimulation of food intake during prolonged exercise is most likely not due to changes of ghrelin.

Food intake and plasma ghrelin response during potato-, rice- and pasta-rich test meals.

OBJECTIVE: Complex carbohydrates such as potato, rice and pasta are frequently consumed accompaniments of meat meals and have different effects on satiety, food intake, glucose, and insulin concentrations. The orexigenic gastric hormone ghrelin contributes to feeding regulation and as yet it is unknown whether there is any differential ghrelin response to these starchy food items corresponding to their effects on food intake. METHODS: In 11 subjects the effect of satiating amounts of potatoes, rice or pasta consumed together with 150 g pork steak was examined on hunger/satiety ratings, food intake, plasma insulin, glucose and ghrelin concentrations. RESULTS: All meals led to comparable quantities of food intake while energy intake was significantly lower after potatoes. Satiety/hunger ratings were significantly different from basal for the entire 4 h period after rice and pasta meals, while they had returned to basal during the 4th hour after potatoes. After rice and pasta insulin rose significantly for 4 h. Ghrelin decreased during the 2nd and 3rd hour. In contrast potatoes stimulated insulin for the initial 2 h only while ghrelin rose significantly by 120 pg/ml over the 4 h period. A significant correlation was observed between ghrelin and hunger ratings while subsequent second meal food and energy intake did not differ irrespective of the preceding ghrelin concentration. CONCLUSION: Compared to rice and pasta satiating amounts of potatoes coingested with meat result in lower energy intake and postprandial insulin concentrations, which is not counterbalanced during subsequent food intake despite higher ghrelin concentrations. The present data support the concept that ghrelin can affect hunger sensations but not necessarily food and energy intake.

Carbamazepine for prevention of oxaliplatin-related neurotoxicity in patients with advanced colorectal cancer: final results of a randomised, controlled, multicenter phase II study.

BACKGROUND: Oxaliplatin-induced neurotoxicity is a growing, relevant clinical problem. In this study we evaluated the efficacy and safety of carbamazepine for prevention of oxaliplatin-associated neuropathy in patients with advanced colorectal cancer. METHODS: Chemotherapeutic treatment consisted of oxaliplatin 85 mg/m(2) given biweekly and weekly folinic acid 500 mg/m(2) followed by a 24-h infusion of 5-FU 2000 mg/m(2) (FUFOX). One cycle consisted of six consecutive weeks of treatment followed by two weeks of rest (=Treatment B). For Treatment A carbamazepine was added in a dosage for targeted plasma levels of 4-6 mg/L. Neurotoxicity was regularly assessed using a specific scale. Moreover, an evaluation of chronic sensory symptoms and a neurologic examination including tests for vibrational sense, strength and deep tendon reflexes were added creating a peripheral neuropathy (PNP) score. RESULTS: The prospectively defined adequate number of patients needed to provide power for the primary outcome could not be achieved. 19 patients were assigned to Treatment A and 17 to Treatment B. At baseline, the distribution of all clinicopathologic variables was comparable between the two groups. Overall response rates were 16% and 24% and overall survival 15.1 months and 17.4 months for Treatment A and Treatment B, respectively. Between Treatment A and Treatment B there were no major differences when considering worst neurotoxicity during the study period (p=0.46). Grade 3/4 neurotoxicity occured in 4 patients with Treatment A vs. 6 patients with Treatment B. There were no major differences between both groups in each category of the PNP score. CONCLUSIONS: Based on the small number of patients and low statistical power of our study definite conclusions regarding efficacy and safety of carbamazepine for prevention of oxaliplatin-associated neuropathy in patients with advanced colorectal cancer cannot be drawn.

Ghrelin response to protein and carbohydrate meals in relation to food intake and glycerol levels in obese subjects.

Obese subjects have lower basal and an attenuated decrease of postprandial plasma ghrelin following carbohydrate-rich meals, while the response to protein is unknown. Therefore, plasma ghrelin levels were examined after ingestion of satiating amounts of a protein- or carbohydrate-rich meal in relation to food and energy intake and hunger/satiety ratings in 30 obese subjects followed 240 min later by ad lib sandwiches. Food intake and hunger/satiety ratings were identical while energy intake was significantly greater after bread (861 +/- 62.7 vs. 441 +/- 50.4 kcal, p < 0.001). Second meal food and energy intake were not different. Ghrelin decreased after bread, but increased by 50 pg/ml (p < 0.001) after meat. The corresponding increase of insulin was 55 vs. 9 microU/ml (p < 0.001). Glycerol levels decreased significantly less after the protein meal compared to carbohydrates. After protein glycerol was significantly correlated to the rise of ghrelin but not insulin. These data demonstrate that, in obese subjects, protein has no different satiating effect than carbohydrate despite divergent ghrelin levels. Energy intake corresponds to energy density of the respective food items. Ghrelin response to both meals is qualitatively similar but quantitatively attenuated compared to normal weight subjects. The relationship between ghrelin and glycerol would support recent observations of a possible role of ghrelin in fat metabolism.

Differential association of basal and postprandial plasma ghrelin with leptin, insulin, and type 2 diabetes.

To gain further insight into the regulatory role of insulin and leptin on plasma ghrelin, 56 normal weight, 128 normoinsulinemic obese, 121 hyperinsulinemic obese, and 30 type 2 diabetic normoinsulinemic and 75 type 2 diabetic hyperinsulinemic obese patients were examined. In the obese subjects, basal hyperinsulinemia was associated with significantly lower ghrelin independent of BMI, age, and leptin. In normoinsulinemic (normal weight and normoinsulinemic obese) subjects, ghrelin was inversely related to stepwise increasing leptin. Multiple regression analysis and matching for insulin revealed a significant negative interaction of ghrelin with leptin but not insulin. In type 2 diabetic normoinsulinemic subjects, ghrelin was significantly lower compared with that in normoinsulinemic obese subjects. In type 2 diabetic hyperinsulinemic subjects, ghrelin was significantly lower than in normoinsulinemic subjects, whereas no further reduction was observed compared with hyperinsulinemic obese subjects. The postprandial decrease was significantly attenuated in normoinsulinemic obese and hyperinsulinemic obese subjects (-214.8 +/- 247 pg/ml [normal weight], -137.6 +/- 107 pg/ml [normoinsulinemic obese], -85.5 +/- 69 pg/ml [hyperinsulinemic obese], P < 0.001; mean +/- SD), whereas type 2 diabetes had no independent postprandial effect. In conclusion, the present data support the concept that leptin could be of importance for suppression of basal ghrelin during moderate weight gain in normoinsulinemic subjects, whereas hyperinsulinemia but not leptin is responsible in more severe obesity. Postprandial suppression of ghrelin is attenuated by as yet unknown mechanisms that are related to body weight but not to insulin or type 2 diabetes.

Postprandial response of plasma ghrelin levels to various test meals in relation to food intake, plasma insulin, and glucose.

Ghrelin is an orexigenic gastric hormone that decreases in peripheral blood after carbohydrate-rich meals but increases after protein ingestion. In the present study plasma ghrelin was determined together with hunger and satiety ratings and with insulin and glucose concentrations after the ingestion of satiating quantities of carbohydrate-, fat-, protein-, fruit-, and vegetable-rich meals in 14 healthy subjects. Four hours later, standardized sandwiches were consumed. After carbohydrate, ghrelin decreased, whereas fat, protein, fruit, and vegetable ingestion significantly increased ghrelin levels. Considering all test meals, no significant correlation existed between changes of ghrelin levels and satiety ratings (r = 0.05; not significant), whereas a significant inverse relationship was observed between plasma ghrelin and insulin levels (r = -0.44; P < 0.001). During the second meal, sandwich consumption was significantly greater after the preceding fruit and vegetable meals, which was significantly correlated with the fourth-hour increase of ghrelin (r = 0.44; P < 0.001). In conclusion, after an overnight fast, ghrelin release depends on the ingested macronutrients and is most likely not a major regulator of acute food intake, although it is of greater importance for the recurrence of hunger and subsequent meal size.

Effect of GIP, GLP-1, insulin and gastrin on ghrelin release in the isolated rat stomach.

Ghrelin release in man depends on the macronutrient composition of the test meal. The mechanisms contributing to the differential regulation are largely unknown. To elucidate their potential role, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), insulin, gastrin and somatostatin were examined on isolated rat stomach ghrelin secretion, which offers the advantage of avoiding systemic interactions. Basal ghrelin secretion was in a range that did not permit to consistently evaluate inhibiting effects. Therefore, the effect of gastrointestinal hormones and insulin was analyzed during vagal prestimulation. GLP-1(7-36)amide 10(-8) and 10(-7) M decreased ghrelin secretion significantly. In contrast, GIP 10(-8) and 10(-7) M augmented not only prestimulated, but also basal ghrelin secretion (p<0.05). Insulin reduced ghrelin at 10(-10), 10(-8) and 10(-6) M (p<0.05). Both gastrin 10(-8) M and somatostatin 10(-6) M also significantly inhibited ghrelin secretion. These data demonstrate that GLP-1(7-36)amide, insulin, gastrin and somatostatin are potential candidates to contribute to the postprandially observed inhibition of ghrelin secretion with insulin being the most effective inhibitor in this isolated stomach model. GIP, on the other hand, could attenuate the postprandial decrease. Because protein-rich meals do not effectively stimulate GIP release, other as yet unknown intestinal factors must be responsible for protein-induced stimulation of ghrelin release.