Effect of gastric bypass on spontaneous growth hormone and ghrelin release profiles

Objective : The purpose of this study was to analyze growth hormone (GH) concentrations in obese women before and after Roux‐en‐Y gastric bypass (RYGBP) and how resulting changes in weight, fat mass, ghrelin levels, and insulin sensitivity affect GH secretion. Research Methods and Procedures : Blood was sampled at 20‐minute intervals for 24 hours in 10 non‐diabetic premenopausal severely obese women before and 6 months after RYGBP. GH concentrations were measured in all samples, and serum ghrelin was collected at five time‐points. Results : After a 27% BMI drop (55.9 ± 6.2 to 40.7 ± 5.8 kg/m²), blunted GH profiles underwent partial recovery. Basal, postprandial, and mean ghrelin concentrations were not changed. A negative correlation was found between mean GH levels and insulin and homeostasis model assessment (p < 0.01). BMI accounted for 54% of GH variation. Discussion : Partial recovery of GH secretion after RYGBP‐induced weight loss suggests that a blunted secretion is not a causal factor of obesity but a consequence of the obese state and does not seem to be ghrelin‐level dependent.     

Obese subjects respond to the stimulatory effect of the ghrelin agonist growth hormone-releasing peptide-2 on food intake

Objective: The administration of the growth hormone (GH) secretagogue GH‐releasing peptide (GHRP)‐2, like ghrelin, increases food intake (FI) in lean healthy men. The aim of this study was to investigate whether this effect occurs in obese subjects and whether it is dose‐dependent. Research Methods and Procedures: Nineteen subjects (10 lean and nine obese), all healthy and weight stable, received a double‐blind randomized subcutaneous infusion of GHRP‐2 at high dose (HD; 1 μg/kg per hour), low dose (0.1 μg/kg per hour), or placebo for 270 minutes over three study visits. Blood for hormone assays was collected through an intravenous forearm catheter. Hunger and fullness were rated on visual analog scales before and after a fixed breakfast (320 kcal at 120 minutes) and a buffet lunch at 240 minutes. Before lunch, subjects received taped instructions to eat as much as they wanted. Results: GHRP‐2 infusion significantly increased ad libitum FI in a dose‐dependent manner by 10.2 ± 3.9% at low dose (p = 0.011) and by 33.5 ± 5.8% at HD (p = 0.000) compared with placebo. Obesity status did not influence the effect of GHRP‐2 on FI. All subjects had greater ratings of appetite before but similar levels of fullness after the meal with the HD GHRP‐2. Serum GH levels increased dose dependently in all subjects. Discussion: The dual stimulatory effect of GHRP‐2 on FI and human GH is dose dependent. Obese individuals retain their ability to respond to GHRP‐2 both in terms of FI and human GH.     

Changes of Body Weight and Plasma Ghrelin Levels after Gastric Banding and Gastric Bypass

Objective: Ghrelin is an enteric peptide with strong orexigenic and adipogenic effects. Plasma ghrelin levels are decreased in obese subjects but increase after weight loss; this increase is not observed after Roux‐en‐Y gastric bypass (RYGB). Prospective and comparative data after adjustable silicone gastric banding (ASGB) have not been reported previously. Research Methods and Procedures: Overnight fasting plasma ghrelin concentration was measured in morbidly obese subjects at baseline and 3, 6, 12, and 24 months after ASGB (n = 8) or RYGB (n = 5) and in nonoperated controls (n = 7). Results: After RYGB, body weight (BW) decreased by 29.5 ± 5.5 kg (mean ± SE, p < 0.001), whereas plasma ghrelin failed to increase significantly (+167 ± 119 pg/mL, not significant). In contrast, after ASGB, BW decreased less (by 22.8 ± 5.9 kg; p < 0.001), and plasma ghrelin significantly increased by 377 ± 201 pg/mL (p = 0.025). Neither BW nor plasma ghrelin changed in nonoperated controls. Plasma leptin decreased in both operated groups (similarly p < 0.05) but not in nonoperated controls. Plasma growth hormone and insulin‐like growth factor 1 were not correlated with changes in plasma ghrelin concentrations. Discussion: Plasma ghrelin levels failed to increase during substantial weight loss after RYGB, but did increase in response to lesser weight loss after ASGB. These findings suggest that the plasma ghrelin response after weight loss is impaired after exclusion of major parts of the stomach and the duodenum (RYGB), and the smaller long‐term weight loss after ASGB compared with RYGB may be due, at least in part, to an absent increase in plasma ghrelin after RYGB.     

Effects of administration of somatostatin-14 and immunoneutralization of somatostatin on endocrine and growth responses in rainbow trout

Injection of somatostatin‐14 (SS‐14) at 5 ng g^?1 body mass (BM) into rainbow trout Oncorhynchus mykiss decreased (P < 0·05, cubic, r² = 0·54) levels of growth hormone (GH) (1·5 ± 0·9 ng ml^?1v. 6·6 ± 0·6 ng ml^?1) over time when compared to controls. Somatostatin‐14 at 50 ng g^?1 BM also decreased (P = 0·064, quadratic; r² = 0·30) levels of GH (3·6 ± 2·1 ng ml^?1v. 6·6 ± 0·6 ng ml^?1) over time compared to controls. In a second study, passive immunization against SS‐14 (1 : 25 dose) increased (P = 0·10, cubic, r² = 0·12) levels of GH (11·0 ± 4·8 ng ml^?1v. 5·2 ± 1·4 ng ml^?1) over time. Passively immunizing against SS‐14 (1 : 50 dose) increased (P < 0·05, cubic, r² = 0·10) levels of GH (8·2 ± 2·3 ng ml^?1v. 5·2 ± 1·4 ng ml^?1) over time compared to controls. Overall, in the active immunization study there was no difference (P > 0·10) in specific growth rate (G) or feed conversion ratio (FCR) between the three treatment groups during the 9 weeks of the study. Only four of the fish immunized against SS‐14, however, developed antibody titres against SS. Compared to controls, these fish exhibited a G of 0·89 ± 0·09 v. 0·56 ± 0·09% per 3 weeks and FCR of 0·80 ± 0·04 v. 1·20 ± 0·05 g g^?1. In SS‐14 immunized fish, levels of GH decreased (P < 0·05) by day 63 while levels of insulin like growth factor‐I (IGF‐I) increased (P < 0·05) by day 42 and 63. These results indicate the hypothalamic hormone SS‐14 regulates GH secretion similarly in rainbow trout as it does in mammals. Active immunization against SS‐14 could improve growth performance in rainbow trout but enhanced G and FCR is dependent upon generation of antibody titres.     

Does Ramadan fasting affect acylated ghrelin and growth hormone concentrations during short-term maximal exercise in the afternoon?

Ghrelin is an important stomach hormone that influences several metabolic activities and influences growth hormone (GH) release in response to change in energy homeostasis. The aim of this study was to investigate the effect of Ramadan fasting on acylated ghrelin and GH concentrations during a short-term maximal exercise. Eleven male soccer players (age, 22.11 ± 1.3 years; height, 1.76 ± 0.2 m; body mass, 75.3 ± 2.2; mean ± SD) were asked to perform a 30-s Wingate test, during which we recorded the peak (PP) and mean (MP) powers and fatigue index. Measurements were performed in the afternoon at 18:00 h, after three different occasions: (i) one week before Ramadan (BR), (ii) the first week of Ramadan (FWR), and (iii) the fourth week of Ramadan (ER). Blood samples were taken before, immediately and 60 min after the exercise. Our results show that PP and MP were affected by Ramadan fasting with a significant decrease during Ramadan (i.e. FWR and ER) in comparison with ER (p < 0.05). However, no significant difference was observed between BR and FWR (p > 0.05). Also, a significant decrease in body weight and body fat percentage was observed during Ramadan in comparison with ER. From diet record analysis, protein, fat, and carbohydrate decreased significantly during FWR (p < 0.01), often with further decreases by ER. A significant increase in plasma concentrations of ghrelin was observed during the ER (p < 0.001) compared with BR and FWR, and GH levels were significantly higher during ER (p < 0.01) in comparison with BR and FWR. However, the 30-s Wingate tests had no significant effect on plasma concentrations of ghrelin before or during Ramadan. Our study shows that the concentrations of ghrelin and GH change in the last week of Ramadan fasting, though it is unclear if these changes are related to the changes in body composition during Ramadan, or if they are responsible for the change in performance at the short-duration anaerobic test.     

Twenty-four-hour ghrelin is elevated after calorie restriction and exercise training in non-obese women

Objective: The purpose of this study was to determine whether chronic energy deficiency achieved with caloric restriction combined with exercise is associated with changes in the 24‐hour profile of ghrelin in non‐obese, pre‐menopausal women. Research Methods and Procedures: Twelve non‐obese (BMI = 18 to 25 kg/m²), non‐exercising women (age, 18 to 24 years) were randomly assigned to a non‐exercising control group or a diet and exercise group. The 3‐month diet and exercise intervention yielded a daily energy deficit of ?45.7 ± 12.4%. Serial measurements were made of body composition, energy balance, and feelings of fullness. Repeated blood sampling over 24 hours to measure ghrelin occurred before and after the study. Results: Significant decreases in body weight, body fat, and feelings of fullness were observed in only the energy‐deficit group (p < 0.05); significant changes in the following ghrelin features were found in only the deficit group (p < 0.05): elevations in baseline (+353 ± 118 pg/mL), lunch peak (+370 ± 102 pg/mL), dinner peak (+438 ± 149 pg/mL), nocturnal rise (+269 ± 77 pg/mL), and nocturnal peak (+510 ± 143 pg/mL). In addition, we found a larger dinner decline (?197 ± 52 pg/mL) and negative correlations between changes in the ghrelin dinner profile and changes in body weight (R = 0.784), 24‐hour intake (R = 0.67), energy deficiency (R = 0.762), and feelings of fullness (R = 0.648; p < 0.05). Discussion: Changes in ghrelin concentrations across the day after weight loss are closely associated with other physiological adaptations to energy deficiency, further supporting the role of ghrelin as a countermeasure to restore energy balance.     

Ghrelin Does Not Influence Gastric Emptying in Obese Subjects

Objective: To evaluate the relationship between fasting plasma concentrations of ghrelin and gastric emptying in obese individuals compared with lean subjects. Research Methods and Procedures: We included 20 obese patients (9 men and 11 women, BMI > 30 kg/m²) and 16 nonobese control subjects (7 men and 9 women, BMI ≤ 25 kg/m²). Gastric emptying of solids (egg sandwich labeled with radionuclide) was measured at 120 minutes with (99m)Tc‐single photon emission computed tomography imaging. Ghrelin and leptin were analyzed by radioimmunoassay and ELISA methods, respectively. Results: The gastric half‐emptying time was similar in obese men and women (67.8 ± 14.79 vs. 66.6 ± 13.56 minutes) but significantly shorter (p < 0.001) than in the control population (men: 88.09 ± 11.72 minutes; women: 97.25 ± 10.31 minutes). Ghrelin levels were significantly lower in obese subjects (131.37 ± 47.67 vs. 306.3 ± 45.52 pg/mL; p < 0.0001 in men and 162.13 ± 32.95 vs. 272.8 ± 47.77 pg/mL; p < 0.0001 in women). A negative correlation between gastric emptying and fasting ghrelin levels was observed only in lean subjects (y = ?0.2391x + 157.9; R² = 0.95). Also, in the lean group, ghrelin was the only significant independent determinant of gastric emptying, explaining 98% of the variance (adjusted R²) in a multiple regression analysis. Discussion: This report shows that, in humans, gastric emptying is faster in obese subjects than in lean controls and that, whereas ghrelin is the best determinant of gastric kinetics in healthy controls, this action is lost in obesity.     

Fasting ghrelin does not predict food intake after short-term energy restriction

Objective: To study the role of ghrelin as a hunger signal during energy restriction and to test the hypothesis that changes in fasting leptin concentrations during energy restriction are associated with changes in fasting ghrelin concentrations. Research Methods and Procedures: Thirty‐five healthy, lean men (23 ± 3 years of age; BMI: 22.3 ± 1.6 kg/m²) participated in a controlled intervention study. Fasting ghrelin and leptin concentrations were measured before and after 2 days of 62% energy restriction and after a 2‐day period of ad libitum food intake. Energy intake during the latter period was assessed. Results: On average, ghrelin concentrations did not change (0.05 μg/liter; 95% confidence interval, ?0.03; 0.12) during energy restriction. Changes in ghrelin concentration during energy restriction were not associated with energy intake during the ad libitum period (r = 0.07; not significant). Ad libitum energy intake was, however, associated with the change in ghrelin concentrations during the same period (r = ?0.34; p = 0.05). Ghrelin and leptin concentrations were not associated. In addition, the ratio of percentage changes in ghrelin and leptin during energy restriction was not correlated with ad libitum food intake after energy restriction (r = ?0.26; p = 0.14). Discussion: Fasting ghrelin concentrations did not rise after a 2‐day energy restriction regimen. Moreover, changes in ghrelin concentrations during energy restriction were not associated with subsequent ad libitum food intake, suggesting that fasting ghrelin does not act as a hunger signal to the brain. The data did not support our hypothesis that leptin suppresses ghrelin levels.     

Nocturnal ghrelin pulsatility and response to growth hormone secretagogues in healthy men

The physiological importance of endogenous ghrelin in the regulation of growth hormone (GH) secretion is still unknown. To investigate the regulation of ghrelin secretion and pulsatility, we performed overnight ghrelin and GH sampling every 20 min for 12 h in eight healthy male subjects [age 37 +/- 5 (SD) years old, body mass index 27.2 +/- 2.9 kg/m2]. Simultaneous GH and ghrelin levels were assessed to determine the relatedness and synchronicity between these two hormones in the fasted state during the overnight period of maximal endogenous GH secretion. Pulsatility analyses were performed to determine simultaneous hormonal dynamics and investigate the relationship between GH and ghrelin by use of cross-approximate entropy (X-ApEn) analyses. Subjects demonstrated 3.0 +/- 2.1 ghrelin pulses/12 h and 3.3 +/- 0.9 GH pulses/12 h. The mean normalized ghrelin entropy (ApEn) was 0.93 +/- 0.09, indicating regularity in ghrelin hormone secretion. The mean normalized X-ApEn was significant between ghrelin and GH (0.89 +/- 0.12), demonstrating regularity in cosecretion. In addition, we investigated the ghrelin response to standard GH secretagogues [GH-releasing hormone (GHRH) alone and combined GHRH-arginine] in separate testing sequences separated by 1 wk. Our data demonstrate that, in contrast to GHRH alone, which had little effect on ghrelin, combined GHRH and arginine significantly stimulated ghrelin with a maximal peak at 120 min, representing a change of 66 +/- 14 pg/ml (P = 0.001 by repeated-measures ANOVA and P = 0.02 for GHRH vs. combined GHRH-arginine by MANOVA). We demonstrate relatedness between ghrelin and GH pulsatility, suggesting either that ghrelin participates in the pulsatile regulation of GH or that the two hormones are simultaneously coregulated, e.g., by somatostatin or other stimuli. Furthermore, the differential effects of GHRH alone vs. GHRH-arginine suggest that inhibition of somatostatin tone may increase ghrelin. These data provide further evidence of the physiological regulation of ghrelin in relationship to GH.     

Ghrelin and the Hyposomatotropism of Obesity

Objective: Human obesity is characterized by growth hormone (GH) deficiency, which appears primarily related to a central pattern of obesity and is reverted on weight loss. As yet, the metabolic basis of the GH deficiency remains to be elucidated. The recently discovered endogenous ligand for the GH secretagogue receptor, ghrelin, stimulates GH secretion when administered to rodents or healthy humans. It may thus be hypothesized that low ghrelin levels underlie the hyposomatropism in obesity. Research Methods and Procedures: We have tested this hypothesis in individuals with widely varying body mass and fat distribution and evaluated whether the improved GH concentrations on weight loss are associated with enhanced ghrelin levels. Results: Both plasma GH and ghrelin levels were reciprocally related with body mass index (r = −0.67, p < 0.001). However, whereas 24-hour GH secretion was negatively related to the visceral fat area (r = −0.72, p < 0.01), ghrelin levels showed a positive relationship with the visceral fat area (r = 0.49, p < 0.02). Weight loss resulted in increased GH secretion (median 24-hour GH area under the curve: 1983 vs. 4024 mU/day before and after weight loss, respectively; p < 0.01) but did not affect ghrelin levels. No relationship could be found between GH and ghrelin plasma levels in obese subjects when comparing diurnal concentration profiles. Discussion: We showed that plasma ghrelin and GH levels are both reciprocally related with body mass index, but no causative relationship could be demonstrated between low ghrelin levels and the hyposomatropism in human obesity.     

Metabolic regulation of growth hormone by free fatty acids, somatostatin, and ghrelin in HIV-lipodystrophy

Human immunodeficiency virus (HIV)-lipodystrophy is a syndrome characterized by changes in fat distribution and insulin resistance. Prior studies suggest markedly reduced growth hormone (GH) levels in association with excess visceral adiposity among patients with HIV-lipodystrophy. We investigated mechanisms of altered GH secretion in a population of 13 male HIV-infected patients with evidence of fat redistribution, compared with 10 HIV-nonlipodystrophic patients and 11 male healthy controls similar in age and body mass index (BMI). Although similar in BMI, the lipodystrophic group was characterized by increased visceral adiposity, free fatty acids (FFA), and insulin and reduced extremity fat. We investigated ghrelin and the effects of acute lowering of FFA by acipimox on GH responses to growth hormone-releasing hormone (GHRH). We also investigated somatostatin tone, comparing GH response to combined GHRH and arginine vs. GHRH alone with a subtraction algorithm. Our data demonstrate an equivalent number of GH pulses (4.1 +/- 0.6, 4.7 +/- 0.8, and 4.5 +/- 0.3 pulses/12 h in the HIV-lipodystrophic, HIV-nonlipodystrophic, and healthy control groups, respectively, P > 0.05) but markedly reduced GH secretion pulse area (1.14 +/- 0.27 vs. 4.67 +/- 1.24 ng.ml(-1).min, P < 0.05, HIV-lipodystrophic vs. HIV-nonlipodystrophic; 1.14 +/- 0.27 vs. 3.18 +/- 0.92 ng.ml(-1).min, P < 0.05 HIV-lipodystrophic vs. control), GH pulse area, and GH pulse width in the HIV-lipodystrophy patients compared with the control groups. Reduced ghrelin (418 +/- 46 vs. 514 +/- 37 pg/ml, P < 0.05, HIV-lipodystrophic vs. HIV-nonlipodystrophic; 418 +/- 46 vs. 546 +/- 45 pg/ml, P < 0.05, HIV-lipodystrophic vs. control), impaired GH response to GHRH by excess FFA, and increased somatostatin tone contribute to reduced GH secretion in patients with HIV-lipodystrophy. These data provide novel insight into the metabolic regulation of GH secretion in subjects with HIV-lipodystrophy.     

Plasma lactate, GH and GH-binding protein levels in exercise following BCAA supplementation in athletes

Summary. Branched chain amino acids (BCAA) stimulate protein synthesis, and growth hormone (GH) is a mediator in this process. A pre-exercise BCAA ingestion increases muscle BCAA uptake and use. Therefore after one month of chronic BCAA treatment (0.2 g kg⁻¹ of body weight), the effects of a pre-exercise oral supplementation of BCAA (9.64 g) on the plasma lactate (La) were examined in triathletes, before and after 60 min of physical exercise (75% of VO₂max). The plasma levels of GH (pGH) and of growth hormone binding protein (pGHBP) were also studied. The end-exercise La of each athlete was higher than basal. Furthermore, after the chronic BCAA treatment, these end-exercise levels were lower than before this treatment (8.6 ± 0.8 mmol L⁻¹ after vs 12.8 ± 1.0 mmol L⁻¹ before treatment; p < 0.05 [mean ± std. err.]). The end-exercise pGH of each athlete was higher than basal (p < 0.05). Furthermore, after the chronic treatment, this end-exercise pGH was higher (but not significantly, p = 0.08) than before this treatment (12.2 ± 2.0 ng mL⁻¹ before vs 33.8 ± 13.6 ng mL⁻¹ after treatment). The end-exercise pGHBP was higher than basal (p < 0.05); and after the BCAA chronic treatment, this end-exercise pGHBP was 738 ± 85 pmol L⁻¹ before vs 1691 ± 555 pmol L⁻¹ after. pGH/pGHBP ratio was unchanged in each athlete and between the groups, but a tendency to increase was observed at end-exercise. The lower La at the end of an intense muscular exercise may reflect an improvement of BCAA use, due to the BCAA chronic treatment. The chronic BCAA effects on pGH and pGHBP might suggest an improvement of muscle activity through protein synthesis. Received January 5, 1999 / Accepted June 17, 1999     

Effect of weight loss on free insulin-like growth factor-I in obese women with hyposomatotropism

Objective: It has been hypothesized that increased free insulin‐like growth factor (IGF)‐I levels generated from an increase in IGF‐binding protein (IGFBP) protease activity could be the inhibitory mechanism for the decreased growth hormone (GH) secretion observed in obese subjects. Research Methods and Procedures: In this study, we determined basal and 24‐hour levels of free IGF‐I and ‐II, total IGF‐I and ‐II, IGFBP‐1, as well as basal IGFBP‐2, ?3, and ?4, acid‐labile subunit (ALS), IGFBP‐1, ?2, and ?3 protease activity, and 24‐hour GH release in obese women before and after a diet‐induced weight loss. Sixteen obese women (age, 29.5 ± 1.4 years) participated in a weight loss program and 16 age‐matched non‐obese women served as controls. Results: Circulating free IGF‐I and 24‐hour GH release were significantly decreased in obese women at before weight loss compared with non‐obese women (1.29 ± 0.12 vs. 0.60 ± 0.09 μg/L; p < 0.001 and 862 ± 90 vs. 404 ± 77 mU/24 hours; p < 0.001, respectively). Free IGF‐I and 24‐hour GH release were not inversely correlated to each other. IGFBP‐1 and ?2 levels were decreased, whereas ALS, IGFBP‐3 and ?4, and IGFBP‐1, ?2, and ?3 protease activity were similar in obese and non‐obese women. Eight of the 16 obese women achieved an average weight loss of 30 ± 5 kg during 26 to 60 weeks of dieting. After the considerable weight loss, significant differences in free IGF‐I, GH release, and IGFBP‐1 and ?2 levels were no longer present between previously obese and non‐obese women. Discussion: We showed that circulating free IGF‐I is markedly decreased in severely obese women and does not per se mediate the concomitant hyposomatotropism. The decreased levels of free IGF‐I seem to be transient and restored to normal levels after weight loss.     

Short‐Term Effects of Gastric Bypass Surgery on Circulating Ghrelin Levels

Objective: To prospectively evaluate the short‐term effects of Roux‐en‐Y gastric bypass (RYGBP) on ghrelin secretion and its relevance on food intake and body weight changes. Research Methods and Procedures: Ghrelin response to a standardized test meal was evaluated in eight obese patients (BMI, 43.5 to 59.1 kg/m²) before and 6 weeks after RYGBP. Ghrelin response was compared with that of an age‐matched group of six normal weight individuals (BMI, 19.6 to 24.9 kg/m²). Results: Fasting serum ghrelin levels were lower in obese subjects compared with controls (p < 0.05). Meal ingestion significantly suppressed ghrelin concentration in controls (p < 0.05) and obese subjects (p < 0.05), albeit to a lesser degree in the latter group (p < 0.05). Despite a 10.3 ± 1.5% weight loss, fasting serum ghrelin levels were paradoxically further decreased in obese subjects 6 weeks after RYGBP (p < 0.05). Moreover, at this time‐point, food intake did not elicit a significant ghrelin suppression. The changes in ghrelin secretion after RYGBP correlated with changes in insulin sensitivity (p < 0.05) and caloric intake (p < 0.05). Discussion: This study showed that the adaptive response of ghrelin to body weight loss was already impaired 6 weeks after RYGBP. Our study provides circumstantial evidence for the potential role of ghrelin in the negative energy balance in RYGBP‐operated patients.     

β‐Cell Function Improvement After Biliopancreatic Diversion in Subjects With Type 2 Diabetes and Morbid Obesity

In subjects with obesity and type 2 diabetes mellitus (T2DM), biliopancreatic diversion (BPD) improves glucose stimulated insulin secretion, whereas the effects on other secretion mechanisms are still unknown. Our objective was to evaluate the early effects of BPD on nonglucose‐stimulated insulin secretion. In 16 morbid obese subjects (9 with T2DM and 7 with normal fasting glucose (NFG)), we measured insulin secretion after glucose‐dependent arginine stimulation test and after intravenous glucose tolerance test (IVGTT) before and 1 month after BPD. After surgery the mean weight lost was 13% in both groups. The acute insulin response during IVGTT was improved in T2DM after BDP (from 55 ± 10 to 277 ± 91 pmol/l, P = 0.03). A reduction of insulin response to arginine was observed in NFG, whereas opposite was found in T2DM. In particular, acute insulin response to arginine at basal glucose concentrations (AIR_basal) was reduced but insulin response at 14 mmol/l of plasma glucose (AIR₁₄) was increased. Therefore, after BPD any statistical difference in AIR₁₄ between NFG and T2DM disappeared (1,032 ± 123 for NFG and 665 ± 236 pmol/l for T2DM, P = ns). The same was observed for Slope_AIR, a measure of glucose potentiation, reduced in T2DM before BPD but increased after surgery, when no statistically significant difference resulted compared with NFG (Slope_AIR after BPD: 78 ± 11 in NFG and 56 ± 18 pmol/l in T2DM, P = ns). In conclusion, in obese T2DM subjects 1 month after BPD we observed a great improvement of both glucose‐ and nonglucose‐stimulated insulin secretions. The mechanisms by which BDP improve insulin secretion are still unknown.     

The effect of caloric restriction interventions on growth hormone secretion in nonobese men and women

Lifespan in rodents is prolonged by caloric restriction (CR) and by mutations affecting the somatotropic axis. It is not known if CR can alter the age‐associated decline in growth hormone (GH), insulin‐like growth factor (IGF)‐1 and GH secretion. To evaluate the effect of CR on GH secretory dynamics; forty‐three young (36.8 ± 1.0 years), overweight (BMI 27.8 ± 0.7) men (n = 20) and women (n = 23) were randomized into four groups; control = 100% of energy requirements; CR = 25% caloric restriction; CR + EX = 12.5% CR + 12.5% increase in energy expenditure by structured exercise; LCD = low calorie diet until 15% weight reduction followed by weight maintenance. At baseline and after 6 months, body composition (DXA), abdominal visceral fat (CT) 11 h GH secretion (blood sampling every 10 min for 11 h; 21:00–08:00 hours) and deconvolution analysis were measured. After 6 months, weight (control: ?1 ± 1%, CR: ?10 ± 1%, CR + EX: ?10 ± 1%, LCD: ?14 ± 1%), fat mass (control: ?2 ± 3%, CR: ?24 ± 3%, CR + EX: ?25 ± 3%, LCD: ?31 ± 2%) and visceral fat (control: ?2 ± 4%, CR: ?28 ± 4%, CR + EX: ?27 ± 3%, LCD: ?36 ± 2%) were significantly (P < 0.001) reduced in the three intervention groups compared to control. Mean 11 h GH concentrations were not changed in CR or control but increased in CR + EX (P < 0.0001) and LCD (P < 0.0001) because of increased secretory burst mass (CR + EX: 34 ± 13%, LCD: 27 ± 22%, P < 0.05) and amplitude (CR + EX: 34 ± 14%, LCD: 30 ± 20%, P < 0.05) but not to changes in secretory burst frequency or GH half‐life. Fasting ghrelin was significantly increased from baseline in all three intervention groups; however, total IGF‐1 concentrations were increased only in CR + EX (10 ± 7%, P < 0.05) and LCD (19 ± 4%, P < 0.001). A 25% CR diet for 6 months does not change GH, GH secretion or IGF‐1 in nonobese men and women.     

Acute exercise has no effect on ghrelin plasma concentrations.

Exercise is a potent, dose-dependent stimulus of growth hormone (GH) secretion. The hypothalamic peptides, GH-releasing hormone (GHRH) and somatostatin are regarded as major regulators of this stimulation. The role of the stomach-derived peptide ghrelin, which has been shown to exert strong GH releasing effects, has not been fully characterized yet. We therefore studied GH and ghrelin plasma concentrations in response to graded levels of exercise in eight healthy young volunteers. After determination of their individual maximal exercise capacity, all individuals underwent a treadmill exercise at 50 %, 70 %, and 90 % of maximum oxygen consumption (VO (2)max) on different days. Maximal GH response to exercise was observed after 40 minutes at 50 % VO (2)max and after 20 minutes at 70 and 90 % VO (2max). GH serum concentrations increased significantly at all three exercise intensities (GH peak concentrations were 5.8 +/- 2.3 ng/ml, 12.0 +/- 3.2 ng/ml, and 9.8 +/- 4.7 ng/ml, respectively). In contrast, ghrelin plasma concentrations remained unchanged at all three workloads. Assuming that the sensitivity of the GH neuroendocrine/metabolic regulation of GH is unaltered, ghrelin does not participate in the regulation of the GH response to exercise in healthy males.     

Infradian rhythmicity in lactogenic hormone (prolactin,growth hormone,cortisol and thyroid hormone) secretion throughout the lactation cycle in mithun cows (Bos frontalis): variation among strains

The role of lactogenic hormones (prolactin, growth hormone, cortisol and thyroid hormone) on lactation yield in Mithun cows as well as their rhythmicity throughout the lactation cycle were studied in Mizoram (n = 4) and Nagaland (n = 7) strain of mithun (Bos frontalis). Blood samples were collected from all the animals from the day of calving to the complete dry off at an interval of 15 days. All the hormones were estimated in the serum by commercially available ELISA kits. Plasma level of cortisol (μg/dl), growth hormone (GH, in ng/ml), prolactin (PRL, in μIU/ml), triiodothyronine (T₃, in nmol/μl) and thyroxin (T₄, in ng/ml) were 20.84 ± 0.29, 28.08 ± 0.56, 9.87 ± 0.20, 27.82 ± 0.56 and 51.33 ± 0.48, respectively, in mithun irrespective of strains during the lactation period. Levels of all the hormones varied significantly (p ≤ 0.01) during different days of lactation cycle but, there was no significant difference among strain. Levels of PRL, GH, cortisol and T₃ were significantly (p < 0.01) higher around calving and declined sharply. The hormones remained in almost steady state during mid-lactation and declined during late lactation. All the hormones stated above were positively correlated with lactational yield thus their role on lactogenesis and galactopoiesis was established.     

Low-dose pramlintide reduced food intake and meal duration in healthy, normal-weight subjects

Objective: We previously reported that a single preprandial injection (120 μg) of pramlintide, an analog of the β‐cell hormone amylin, reduced ad libitum food intake in obese subjects. To further characterize the meal‐related effects of amylin signaling in humans, we studied a lower pramlintide dose (30 μg) in normal‐weight subjects. Research Methods and Procedures: In a randomized, double‐blind, placebo‐controlled, cross‐over study, 15 healthy men (age, 24 ± 7 years; BMI, 22.2 ± 1.8 kg/m²) underwent a standardized buffet meal test on two occasions. After an overnight fast, subjects received a single subcutaneous injection of pramlintide (30 μg) or placebo, followed immediately by a standardized pre‐load meal. After 1 hour, subjects were offered an ad libitum buffet meal, and total caloric intake and meal duration were measured. Results: Compared with placebo, pramlintide reduced total caloric intake (1411 ± 94 vs. 1190 ± 117 kcal; Δ, ?221 ± 101 kcal; ?14 ± 9%; p = 0.05) and meal duration (36 ± 2 vs. 31 ± 3 minutes; Δ, ?5.1 ± 1.4 minutes; p < 0.005). Visual analog scale profiles of hunger trended lower and fullness higher during the first hour after pramlintide administration. In response to the buffet, hunger and fullness changed to a similar degree after pramlintide and placebo, despite subjects on pramlintide consuming 14% fewer kilocalories. Visual analog scale nausea ratings remained near baseline, without differences between treatments. Plasma peptide YY, cholecystokinin, and ghrelin concentrations did not differ with treatment, whereas glucagon‐like peptide‐1 concentrations after meals were lower in response to pramlintide than to placebo. Discussion: These observations add support to the concept that amylin agonism may have a role in human appetite control.     

Chemiluminescent immunoassay (CLIA) for salmon growth hormone (GH)

A highly sensitive and specific chemiluminescent immunoassay (CLIA) was developed for quantification of growth hormone (GH) in salmonid species. The CLIA for salmon GH was performed using the sandwich method with anti-GH IgG as the first antibody and chemiluminescent acridinium ester-labelled specific anti-GH F(ab′)₂ as the second antibody. The measurable range of salmon GH in the CLIA was 39–1250 pg/mL using a short assay (1 day) protocol and 3.9–125 pg/mL in a longer (2-day) assay. The dilution curve in the CLIA of serum from masu salmon (Oncorhynchus masou) was parallel to the standard curve of recombinant chum salmon (Oncorhynchus keta) GH. Seasonal changes of serum GH levels were measured in 1 year-old masu salmon cultivated in a pond from March to November. Their serum GH levels increased during smoltification from March to April, achieved a maximum level of 21 ng/mL in August, and then declined gradually to 11 ng/mL in October. © 1997 John Wiley & Sons, Ltd.