Biomedical subjects

B Otto

Publications and source records attributed to B Otto.

At least 19 recordsLinked to original sources

PubMed2007

[Neurosyphilis: important differential diagnosis of herpes simplex encephalitis].

Diagnosis of herpes simplex encephalitis in the acute stage is based on clinical symptoms (nonspecific prodromi, neuropsychological deficits, epileptic seizures) in combination with typical CSF abnormalities (lymphomonozytic pleocytosis) and MR imaging abnormalities assumed to be typical for herpes simplex encephalitis (increased fluid-attenuated inversion recovery and T2 hyperintensities in the mesiotemporal lobe region). Definite diagnosis of herpes simplex encephalitis is based on positive polymerase chain reaction in the CSF, usually available some days after hospital admission. Suspected herpes simplex encephalitis requires immediate treatment with acyclovir. Bacterial encephalitis caused by spirochetes may present with similar features but requires different treatment. This should therefore be considered in the differential diagnosis of herpes simplex encephalitis. We report a young patient with neurosyphilis whose correct diagnosis could be made only several days after beginning specific treatment.

Adult↗

PubMed2006

Peptide YY release in anorectic patients after liquid meal.

Fasting and postprandial levels of human peptide YY (PYY) were recently found to be lower in obesity. To investigate whether PYY levels are correspondingly high in patients with anorexia nervosa, PYY concentrations were analyzed under basal conditions and in response to a liquid meal. We investigated PYY plasma levels in 16 female anorectic (BMI 15.2+/-0.3 kg/m2) and seven lean subjects (BMI 21.3+/-0.6 kg/m2) before and after ingestion of a liquid meal (250 kcal; 15% protein, 55% carbohydrates, and 30% fat). PYY levels were analyzed using PYY ELISA (DSL, USA). Values are given as mean+/-SEM. Basal PYY levels in anorectic patients (89.0+/-14.4 pg/mL) were not significantly different from lean subjects (64.1+/-12.1 pg/mL). Postprandial PYY levels in healthy volunteers increased significantly after 20 and 60 min (80.4+/-12.7 and 96.0+/-19.9 pg/mL, respectively). In anorectic women PYY was increased at 20 min (137.9+/-19.5 pg/mL) and at 60 min (151.3+/-19.2 pg/mL). No difference was found between both groups. We conclude that basal and postprandial PYY levels in normal weight women are not different from anorectic patients. We could not confirm the recently published blunted postprandial PYY response in anorexia, a finding that merits further study.

Adult↗

PubMed2006

Effect of human body weight changes on circulating levels of peptide YY and peptide YY3-36.

BACKGROUND: Recent findings suggest that low plasma peptide YY (PYY) levels may contribute to diet-induced human obesity and justify PYY replacement therapy. Although the pharmacological value of PYY is controversial, further study of the secretion of the precursor PYY(1-36) and the pharmacologically active PYY(3-36) is indicated to determine the potential role in energy balance regulation. AIM: Our objective was to determine the effects of acute and chronic changes in human body weight on circulating levels of the putative satiety hormone peptide YY. DESIGN: Total plasma PYY levels (PYY(1-36) + PYY(3-36)) were measured in 66 lean, 18 anorectic, 63 obese, and 16 morbidly obese humans. In addition, total PYY was measured in 17 of the obese patients after weight loss and in the 18 anorectic patients after weight gain. Fasting PYY(3-36) levels were measured in 17 lean and 15 obese individuals. RESULTS: Fasting total plasma PYY levels were highest in patients with anorexia nervosa (80.9 +/- 12.9 pg/ml, P < 0.05) compared with lean (52.4 +/- 4.6 pg/ml), obese (43.9 +/- 3.8 pg/ml), or morbidly obese (45.6 +/- 11.2 pg/ml) subjects. In obese patients, weight loss of 5.4% was associated with a 30% decrease in fasting total PYY plasma levels. In anorectic patients, weight gain had no effect on fasting PYY. PYY(3-36) levels did not differ between lean (96.2 +/- 8.6 pg/ml) and obese (91.5 +/- 6.9 pg/ml) subjects. CONCLUSION: Our findings do not support a role for abnormal circulating PYY in human obesity. We conclude that circulating PYY levels in humans are significantly elevated in anorexia nervosa and, given the controversially discussed anorectic effect of PYY, could theoretically contribute to that syndrome.

Adult↗

PubMed2006

Arabinoxylan consumption decreases postprandial serum glucose, serum insulin and plasma total ghrelin response in subjects with impaired glucose tolerance.

OBJECTIVE: Arabinoxylan (AX) consumption is associated with metabolic improvement during diabetes and with modulation of ghrelin, an orexigenic gut hormone. The effect of AX consumption on ghrelin secretion in disturbed metabolic states is unknown. Therefore, we investigated the postprandial responses to AX consumption of serum glucose, insulin and triglycerides and plasma total and acylated ghrelin in subjects with impaired glucose tolerance (IGT). DESIGN: Randomized, single-blind, controlled, crossover intervention trial. SUBJECTS: Seven female and four male adults with IGT, aged 55.5 years, and body mass index (BMI) 30.1 kg/m(2). INTERVENTION: Subjects received either placebo or 15 g AX supplement for 6 weeks with a 6-week washout period in-between. MAIN OUTCOME MEASUREMENTS: Postprandial responses of serum glucose, insulin and triglycerides, and plasma total and acylated ghrelin after a liquid meal challenge test (LMCT) measured at the beginning and at the end of the dietary intervention at -20, -5, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210 and 240 min. RESULTS: After LMCT, AX consumption resulted in lower postprandial responses in serum glucose, insulin and triglycerides (P<0.05). Compared to placebo, total plasma ghrelin was also reduced by 42+/-8 pg/ml (P<0.001) after AX consumption with no difference in plasma acylated ghrelin. CONCLUSION: AX consumption improved postprandial metabolic responses after an LMCT in subjects with IGT and reduced total ghrelin response. However, acylated ghrelin responses were unchanged, suggesting that the acylated ghrelin-mediated orexigenic regulation is not improved as only total plasma ghrelin decreased.

Aged↗

PubMed2006

Regulation of ghrelin is related to estimated insulin sensitivity in obese children.

OBJECTIVE: To investigate whether ghrelin concentrations and their changes during weight loss in obese children are associated with parameters of glucose and insulin metabolism. DESIGN: Total plasma ghrelin, insulin and glucose were measured during oral glucose tolerance testing before and after diet-induced weight loss over 6 weeks. SETTING: In-patient rehabilitation program in a pediatric hospital. PARTICIPANTS: Twenty-three obese children (age 10-16 years) and 11 normal weight controls (age 10-15 years). OUTCOME MEASURES: Changes in ghrelin concentrations during weight loss and correlation analysis of changes in ghrelin and changes in parameters of glucose and insulin metabolism. After data collection, subgroup analysis of obese patients with high, medium and low estimated insulin sensitivity whole-body insulin sensitivity index (WBISI) was performed. RESULTS: Weight loss increased the area under the curve (AUC) of ghrelin by 26% (P<0.001). The increase in ghrelin AUC correlated significantly with improved estimated insulin sensitivity (WBISI) (r=0.69, P<0.001). The independent predicting effect of WBISI was confirmed in multivariate analysis. In children with low WBISI, ghrelin reached the level of control values after weight loss. In children with high WBISI, ghrelin increased markedly above control levels. CONCLUSIONS: Changes in ghrelin are independently associated with changes in glucose and insulin metabolism. The increase in plasma ghrelin above control levels was limited to obese children with high WBISI.

Adolescent↗

PubMed2006

Glucagon suppression of ghrelin secretion is exerted at hypothalamus-pituitary level.

CONTEXT: The mechanisms underlying the well-known glucagon-induced satiety effect are unclear. Recently, we showed that glucagon induces a remarkable decrease in the orexigenic hormone ghrelin that might be responsible for this effect. OBJECTIVE: The objective of this study was to evaluate the putative role of the hypothalamic pituitary axis in glucagon's suppressive effect on ghrelin secretion. DESIGN, SUBJECTS, AND METHODS: Prospectively, we studied the endocrine and metabolic responses to im glucagon administration in 22 patients (16 males; age, 21-68 yr; body mass index, 28.1 +/- 1.1 kg/m(2)) with a known hypothalamic-pituitary lesion and at least one pituitary hormone deficiency. Control experiments were performed in 27 healthy subjects (15 males; age, 19-65 yr; body mass index, 25.5 +/- 0.9 kg/m(2)). RESULTS: The suppression of ghrelin by glucagon measured as area under the curve(240 min) was significantly greater in controls when compared with patients (P < 0.01). Although there was a significant decrease in ghrelin in controls (P < 0.001), ghrelin was almost unchanged in patients (P = 0.359). Changes in glucagon, glucose, and insulin levels were comparable between both groups. CONCLUSIONS: We show that the hypothalamic-pituitary axis plays an essential role in the suppression of ghrelin induced by im glucagon administration. Glucagon significantly decreases ghrelin levels in healthy subjects. However, in the absence of an intact hypothalamic-pituitary axis, this effect was abolished. The mechanisms responsible for our observation are unlikely to include changes in glucose or insulin levels.

Adult↗

PubMed2006

Increase in adiponectin levels during pioglitazone therapy in relation to glucose control, insulin resistance as well as ghrelin and resistin levels.

Glitazones increase the secretion of the adipocyte-derived hormone adiponectin. Furthermore, the gastric signal peptide ghrelin is known to suppress adiponectin expression in adipocyte cell culture models. It is not known whether the increase in adiponectin during glitazone therapy is due to a suppression of ghrelin levels, a decrease of resistin concentrations or an amelioration of glucose control. In 10 patients (age 71+/-9 yr, body mass index 29.9+/-3.6 kg/m(2), HbA1c 6.9+/-0.5%) with Type 2 diabetes, who had already been treated with sulfonylureas, we additionally initiated a pioglitazone therapy (30 mg/day) for 12 weeks. To investigate the pioglitazone effect independently of blood glucose, glycosylated hemoglobin (HbA1c) was kept unchanged by reducing the daily dose of sulfonylurea if necessary. Ghrelin concentration [radioimmunoassay (RIA), Phoenix Pharmaceuticals, Mountain View, CA, USA], adiponectin levels [enzyme-linked immunosorbent assay (ELISA), Biovendor, Heidelberg, Germany] as well as resistin concentrations (ELISA, Linco Research, St. Charles, MO, USA) were measured before and after pioglitazone. Glucose control remained unchanged within the 12-week pioglitazone therapy (HbA1c 6.9+/-0.5% before vs 6.8+/-0.6% after pioglitazone) while body weight increased from 86.6+/-9.2 to 88.0+/-9.4 kg (p<0.05), and insulin concentration decreased from 19.6+/-5.7 to 10.1+/-1.6 microU/ml (p<0.05). Adiponectin concentration increased in all patients from 7.70+/-2.47 to 23.33+/-8.28 microg/ml (p<0.01), while resistin concentrations tended to decrease (by 15%; p=0.059). However, ghrelin remained unchanged during therapy. No correlations were observed either between ghrelin, resistin, insulin and adiponectin, or between body weight and hormone plasma levels. The increase in adiponectin levels during pioglitazone therapy seems to be at least partly independent of blood glucose and insulin concentration as well as of ghrelin levels, and it was not associated with a decrease in resistin concentrations.

Adiponectin↗

PubMed2005

A prospective study of serum ghrelin levels in patients treated with clozapine.

We investigated serum ghrelin levels (SGL) in 12 patients with schizophrenia over a 10-week period after initiation of clozapine treatment. In contrast to increments of body mass indices (BMI, kg/m2) and serum leptin levels (SLL), no significant change in SGL was detected. Inverse correlations between delta SGL and delta SLL did not reach statistical significance. Linear mixed model analysis could not detect effects of age, sex, BMI, SLL and serum clozapine levels on SGL. Our results do not support a causal involvement of ghrelin in clozapine-related weight gain.

Adult↗

PubMed2005

Ghrelin is not suppressed in hyperglycemic clamps by gastric inhibitory polypeptide and arginine.

UNLABELLED: Systemic ghrelin concentration falls rapidly after nutrient ingestion in vivo. The effect incretins on ghrelin secretion in humans remains unclear. We quantified circulating ghrelin concentrations under hyperglycemic conditions combined with infusion of gastric inhibitory polypeptide (GIP) and arginine. METHODS: Eight healthy volunteers were studied with a hyperglycemic clamp followed by addition of GIP (2 pmol.kg(-1).min(-1), 60-115 min) and an arginine-bolus and -infusion (10 mg.kg(-1).min(-1), 90-115 min). RESULTS: Hyperglycemia alone increased circulating insulin concentrations (p<0.01), and decreased ghrelin concentrations to 89.8% of basal (p=0.208). GIP-infusion resulted in circulating insulin concentration of 1109+/-942 pmol/l (p<0.02) and no further decrease of ghrelin (86.2% of baseline, p=0.050). Under arginine- and GIP-infusion together, insulin concentrations increased progressively to 3005+/-1604 pmol/l (p<0.01) without further decreasing in ghrelin concentrations (98.9% of baseline, p=0.575). CONCLUSIONS: Hyperglycemic hyperinsulinemia and further increases of hyperinsulinemia to supraphysiological and high supraphysiological concentrations under GIP- and arginine-infusion do not significantly decrease ghrelin concentrations in healthy subjects. Moreover, there is no dose-dependent suppression of ghrelin by insulin in the hyperglycemic condition. Neither GIP nor arginine affected ghrelin release.

Adult↗

PubMed2005

Postprandial ghrelin release in anorectic patients before and after weight gain.

The appetite-modulating hormone ghrelin transmits changes in food intake to the central nervous system. In patients with anorexia nervosa, weight gain reduces elevated fasting ghrelin levels to normal, however, less is known about the effects on postprandial ghrelin levels. In 20 female anorectic in-patients (25.6 +/- 1.0 years; body mass index (BMI) 15.1 +/- 0.3 kg/m2) a standardized test with 250 ml fluid meal (250 kcal: 9.4 g protein, 34.4 g carbohydrates, and 8.3 g fat) was performed at three different times (at admission, after partial weight gain of at least 2 kg, and at discharge) and compared to healthy controls (n = 6; BMI 21.1 +/- 0.7 kg/m2). Plasma ghrelin levels were measured preprandially as well as 20 and 60 min postprandially by a commercially available radioimmunoassay (Phoenix Pharmaceuticals, USA). At admission plasma ghrelin levels significantly decreased postprandially (from 871.9 +/- 124 to 620.3 +/- 80 pg/ml 60 min after meal; P < 0.005). After partial weight gain (2.8 +/- 0.1 kg; BMI 16.1 +/- 0.3 kg/m2) postprandial ghrelin concentrations decreased from 597.0 +/- 79 to 414.7 +/- 39 pg/ml (P < 0.0001), at discharge (weight gain: 7.6 +/- 0.5 kg; BMI 17.9 +/- 0.4 kg/m2) from 570.4 +/- 78 to 395.4 +/- 44 pg/ml (P < 0.0001). Mean postprandial ghrelin decrease was not significantly different between the three tests (29, 25, and 26%, respectively) or to controls (20%). In anorectic patients mean postprandial ghrelin decrease did not change during weight gain. These findings indicate that in anorexia nervosa the suppression of ghrelin release by acute changes of energy balance (feeding) is not disturbed and that it is independent from chronic changes in energy balance (weight gain).

Adult↗

PubMed2005

Arabinoxylan-enriched meal increases serum ghrelin levels in healthy humans.

Soluble fibre like arabinoxylan (AX) is thought to have beneficial effects on metabolism. In this study, we investigated the effect of a breakfast enriched in AX fibre on glucose, insulin and ghrelin values. AX-enriched and control breakfasts were served to fifteen young volunteers (nine female, six male). Glucose, insulin and ghrelin responses were measured after the meal. To avoid effects from differences in glucose metabolism, further analysis was restricted to those subjects with known normal glucose regulation (seven female, four male). The AX fibre-enriched breakfast did not significantly change glucose levels for two hours after breakfast, but decreased insulin levels in the entire cohort (p = 0.035). Glucose response was also not significantly different in subjects with normal glucose regulation (p = 0.367), and the insulin responses after an AX-enriched breakfast showed only a tendency towards lower values (p = 0.065). Nevertheless, plasma ghrelin two hours after AX-enriched breakfast was higher than after the control meal (396.1 +/- 36.4 pg/ml vs. 328.3 +/- 32.6 pg/ml, p < 0.001). In subjects with normal glucose regulation, the AX-enriched breakfast increased ghrelin levels without any significant difference in glucose or insulin response. This effect is therefore unlikely to be mediated by insulin, but the underlying mechanism remains to be elucidated.

Adult↗

PubMed2005

Adaptation of the hypothalamic-pituitary hormones during intensive endurance training.

OBJECTIVE: Physical activity leads to changes in the hypothalamic-pituitary hormonal system. However, acute and long-term adaptations have not yet been precisely characterized. In this study, the changes of the hormonal system as a result of marathon training and running a marathon were examined. In particular, we focused on adaptations of the hypothalamic-pituitary-adrenocortical (HPA) axis, regarding the activation or inactivation of cortisol to cortisone by the 11beta-hydroxysteroid-dehydrogenase system (11beta-HSD). DESIGN: Patient measurements: 8 healthy women and 11 healthy men volunteered for this study. Blood samples, 24-h urine and a dexamethasone suppression test were analysed for metabolic and hormonal parameters at five different dates 12 weeks around a marathon. RESULTS: Cortisol and ACTH values decreased significantly 2 days after the marathon, whereas the activity of the whole body 11beta-HSD-1 was up-regulated. An increased suppression of cortisol levels was observed in the dexamethasone suppression test after 6 weeks of reduced training levels. Ghrelin was elevated 2 days after the marathon. Only minor changes in the other hypothalamic-pituitary-hormonal axes could be observed. However, the free androgen index increased significantly after 6 weeks of reduced training. CONCLUSIONS: The HPA system appeared to become chronically activated by continuous physical training and therefore less sensitive to the dexamethasone suppression test. The acute stress of the marathon led to a central exhaustion of the HPA system with a paracrine counteraction by the activation of the 11beta-HSD system. Changes in the other hypothalamic-pituitary hormonal axes were the result of long-term differences in training levels and were not altered by the marathon.

Adaptation, Physiological↗

PubMed2005

mu-Opiate receptor agonist loperamide blocks bethanechol-induced gallbladder contraction, despite higher cholecystokinin plasma levels in man.

UNLABELLED: mu-Opiate receptor agonists, such as loperamide, influence biliary excretion and suppress cholecystokinin (CCK)-induced gallbladder contraction. Loperamide decreases cholinergic mechanisms, like pancreatic polypeptide (PP) release, while muscarinic agonist (bethanechol)-induced PP release remains unaffected. The effects of loperamide on gallbladder contraction and peptide release were performed to resolve this discrepancy. METHODS: Six subjects (27.6 +/- 2.0 years) received bethanechol (12.5, 25 and 50 microg kg(-1) h(-1) continuously over 40 min) after oral 16 mg loperamide (vs placebo) in a crossover design. Gallbladder volume and plasma levels of CCK, PP, motilin, gastrin, neurotensin, cholylglycine were measured regularly. RESULTS: Bethanechol significantly reduced gallbladder volume (26.7 +/- 1.9 to a nadir of 15.3 +/- 2.2 mL, P < or = 0.05), and this action was inhibited by loperamide. Basal CCK levels increased significantly after loperamide. Incremental integrated CCK release after bethanechol was higher under loperamide (P < or = 0.05), as placebo CCK release was significantly decreased under bethanechol (2.0 +/- 0.4-0.8 +/- 0.3 pmol L(-1)). In both settings, PP levels were significantly increased after bethanechol, while release of neurotensin, motilin, gastrin and cholylglycine was unaffected. CONCLUSION: The mu-opiate receptor agonist loperamide inhibits bethanechol-induced gallbladder contraction. This effect is not mediated by inhibition of CCK release, as loperamide even enhances basal CCK plasma levels. As cholinergic mechanisms, like bethanechol-induced incremental PP release, were unaffected, mu-opiate agonists might influence gallbladder contraction via vagal-cholinergic pathways.

Adult↗

PubMed2005

Glucagon inhibits ghrelin secretion in humans.

OBJECTIVE: It is well known that i.m. glucagon administration stimulates GH and cortisol release in humans, although the mechanisms are unclear. These effects are similar to those described for ghrelin on somatotroph and corticotroph function. The aim of the present study was to investigate the role of ghrelin in mediating the stimulatory effects of glucagon and to evaluate the effect of glucagon on ghrelin secretion. DESIGN AND METHODS: We studied the endocrine and metabolic response to i.m. glucagon administration in 24 subjects (14 men, 10 women; age 19-65 years; body mass index, 25.3 +/- 1 kg/m(2)), who were shown to have an intact anterior pituitary function as evaluated before enclosure. RESULTS: Serum ghrelin concentrations fell significantly at 30, 60, 120 and 180 min after glucagon administration (means +/- s.e.m.; baseline, 377.9 +/- 34.5 pg/ml; nadir, 294.6 +/- 28.3 pg/ml (60 min); P < 0.01). Conversely, i.m. glucagon elicited an increase in GH (baseline, 1.5 +/- 0.4 microg/l; peak, 14.2 +/- 2.7 microg/l (180 min); P < 0.01) and cortisol concentrations (baseline, 452.6 +/- 35.2 nmol/l; peak, 622.1 +/- 44 nmol/l (180 min); P < 0.01). The changes in ghrelin concentration at both 120 and 180 min were still significant after correction for glucose and insulin (P < 0.05). CONCLUSIONS: We show that i.m. glucagon decreases ghrelin significantly. Therefore, the already known stimulatory effects of i.m. glucagon on cortisol and GH are not mediated by a change in ghrelin concentrations. The mechanisms underlying the ghrelin suppression after i.m. glucagon are unlikely to include glucose or insulin variations and need to be further elucidated.

Adult↗

PubMed2005

Membrane proteinase 3 and Wegener's granulomatosis.

Proteinase 3 (PR3) is found in neutrophil and monocyte lysosomal granules. Anti-neutrophil cytoplasmatic antibodies (ANCA) with specificity for PR3 are characteristic for patients with Wegener's granulomatosis. The interaction of ANCA with neutrophilic ANCA antigens is necessary for the development of ANCA-associated diseases. ANCA bind to membrane-expressed PR3 and induce full-blown activation in primed neutrophils. We discuss two different aspects of membrane PR3 (mPR3). The first aspect is the amount of PR3 and mechanisms controlling this issue. The second aspect is the presence of two neutrophil subsets that differ in the mPR3 expression phenotype.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed2004

Effects of xenon anaesthesia on intestinal oxygenation in acutely instrumented pigs.

BACKGROUND: Xenon is a narcotic gas that might be able to replace volatile anaesthetics or nitrous oxide due to its favourable pharmacological properties, such as providing haemodynamic stability. Intestinal oxygenation is affected by most volatile anaesthetics as a result of cardiodepressive effects. Reducing oxygenation of the gut might be a factor leading to perioperative organ dysfunction. This animal study was designed to assess the effects of xenon on intestinal oxygenation. METHODS: After ethical approval, 24 anaesthetized, acutely instrumented pigs were randomly assigned to three groups: nine animals received xenon anaesthesia with inspiratory concentrations of 0, 20, 50 and 65% in addition to their basic i.v. anaesthesia, nine animals served as a study control group, and five animals were used to assess model stability. Measurement of systemic and regional haemodynamic and oxygenation parameters was made 30 min after changing the xenon concentration. RESULTS: Xenon elicited dose-dependent systemic haemodynamic changes: heart rate and cardiac output decreased by 30%, while mean arterial pressure was stable. Superior mesenteric artery blood flow was lower in the xenon group. Vascular resistance of the superior mesenteric artery increased. The small intestinal oxygen supply decreased with increasing xenon concentration; the mucosal tissue oxygen partial pressure decreased but did not reach hypoxic (<5 mm Hg) values. Serosal tissue oxygen partial pressure was maintained. CONCLUSIONS: Xenon, in addition to basic i.v. anaesthesia, elicited a decrease in cardiac output and maintained mean arterial pressure. Intestinal oxygenation was maintained, although regional macrohaemodynamic perfusion decreased. Xenon does not impair intestinal oxygenation under physiological conditions.

Anesthetics, Combined↗

PubMed2004

Endogenous and exogenous glucocorticoids decrease plasma ghrelin in humans.

OBJECTIVE: The orexigenic and adipogenic peptide hormone ghrelin is predominantly produced and secreted by the stomach and seems to transduce changes in food intake to specific neuronal circuits in the brain. The activity of ghrelin also includes stimulatory effects on the corticotropic system. However, little is known about the influence of glucocorticoids on ghrelin levels. We therefore studied human plasma ghrelin levels in the presence and absence of elevated glucocorticoid levels of either endogenous or exogenous origin. METHODS: Plasma ghrelin levels were measured in five patients with chronic hypercortisolism (aged 29-58, median 46 years) due to Cushing's syndrome before and after successful surgery for the adenoma, and in eight healthy controls (aged 24-39, median 27.5 years) before and after 30 mg prednisolone (for 5 days) once a day in the morning (median body mass index (BMI) 22.7 kg/m(2)). Plasma ghrelin levels were measured with a commercially available radioimmunoassay. RESULTS: In patients with Cushing's syndrome, plasma ghrelin levels were low (median 363.2 pg/ml, range 161.9-525.7 pg/ml) and significantly increased by 26.6% (P=0.04) after successful surgery, while BMI decreased (median 26.2-24.0 kg/m(2), P=0.04). A strong negative correlation (r=-0.9, P=0.04) between changes in BMI and plasma ghrelin was observed. In healthy controls, plasma ghrelin levels (median 288.7 pg/ml, range 119.6-827.8 pg/ml) were significantly suppressed by 18.3% (P=0.04) after prednisolone treatment. CONCLUSIONS: We have shown for the first time that plasma ghrelin levels are decreased under endogenously or exogenously induced hypercortisolism, making ghrelin an unlikely candidate for causing the changes in energy balance or body composition characteristic of Cushing's disease. However, the reduced ghrelin secretion could reflect a compensation mechanism in reaction to the metabolic consequences of chronic hypercortisolism.

Adult↗

PubMed2003

Post-prandial decrease of human plasma ghrelin in the absence of insulin.

Ghrelin is the most powerful orexigenic hormone in mammalian physiology. Ghrelin plasma concentrations increase prior to meal onset, but decrease post-prandially. We and others reported previously that insulin reduces circulating ghrelin levels and might therefore be a driving force for post-prandial suppression of ghrelin. To test the influence of insulin on post-prandial ghrelin regulation, a patient with Type I diabetes with complete insulin deficiency received a low glycemic index meal and subsequently an additional high glycemic index meal in the absence of insulin substitution. Subsequently, a sc injection of 0.08 IU Lispro insulin per kg body weight was given. Results were compared to those of a healthy control subject matched for sex, age and body mass index, which was undergoing the same test series (without Lispro bolus) in the presence of endogenous post-prandial insulin secretion. A substantial decrease of plasma ghrelin levels was observed in the insulin-deficient patient following low glycemic index carbohydrate load (27% plasma ghrelin decrease). The subsequent exposure to a high glycemic index meal resulted in a slight additional reduction of ghrelin levels (32% from baseline), while Lispro bolus did not induce further changes in circulating ghrelin (27% of baseline at termination). This post-prandial response was comparable to that of the healthy control subject (33% reduction after the first meal, 40% after the second meal). These data tentatively suggest that post-prandial secretion of ghrelin is not exclusively regulated by plasma insulin or plasma glucose but may depend on other metabolic factors yet to be identified.

Adult↗