Hyperglycaemia suppresses the secretion of ghrelin, a novel growth-hormone-releasing peptide: responses to the intravenous and oral administration of glucose

Nakagawa, Eiichiro; Nagaya, Noritoshi; Okumura, Hiroyuki; Enomoto, Mitsunobu; Oya, Hideo; Ono, Fumiaki; Hosoda, Hiroshi; Kojima, Masayasu; Kangawa, Kenji

doi:10.1042/cs1030325

Cited by 166 publications

(98 citation statements)

References 11 publications

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“…This is in agreement with a recent study with obese children. 23 However, there is ongoing debate whether glucose itself 13,24 or the accompanying rise in insulin levels decrease ghrelin as suggested by other authors. 12 A rise in ghrelin levels after weight loss has been demonstrated earlier in adults 8 and more recently in children, who were younger than in our study.…”

Section: Discussionmentioning

confidence: 99%

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

Krohn

Boczan

Otto³

et al. 2006

Int J Obes

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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 dietinduced 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% (Po0.001). The increase in ghrelin AUC correlated significantly with improved estimated insulin sensitivity (WBISI) (r ¼ 0.69, Po0.001). 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.

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Section: Discussionmentioning

confidence: 99%

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

Krohn

Boczan

Otto³

et al. 2006

Int J Obes

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show abstract

Section: Discussionmentioning

confidence: 99%

“…A number of studies have shown ghrelin to decrease in response to oral (Caixas et al, 2002;Nakagawa et al, 2002;Shiiya et al, 2002) or i.v. glucose (Nakagawa et al, 2002;Shiiya et al, 2002;Briatore et al, 2003), but others do not (Schaller et al, 2003). An inhibitory role of insulin on ghrelin has also been shown in some (Mohlig et al, 2002;Saad et al, 2002;Flanagan et al, 2003) but not all (Caixas et al, 2002;Schaller et al, 2003) studies.…”

Section: Discussionmentioning

confidence: 99%

Effect of high-fat meals and fatty acid saturation on postprandial levels of the hormones ghrelin and leptin in healthy men

et al. 2005

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Objective: Ghrelin and leptin play a role in control of food intake and adiposity but mechanisms regulating these hormones in man are poorly defined and evidence that dietary fats may have adverse effects is inconclusive. We investigated whether high-fat meals, which differed in saturated fatty acid (SFA) content acutely modified these hormones. Design: Randomised, double-blind, crossover trial. A high-fat (HF) test meal (5974 g fat; 71% of energy as fat) was given for breakfast on two occasions. Meals comprised either high (B70:30) or low (B55:45) saturated:unsaturated fatty acid (SFA:USFA) ratio. Fasting and postprandial measurements of serum total ghrelin (RIA), leptin (enzyme-linked immunosorbent assay (ELISA)) and insulin (RIA) were made over 6 h. Postprandial measurements were also made at 10 and 24 h following a fat-exclusion lunch, snack and dinner. Subjects: A total of 18 lean, healthy men. Results: There was no significant effect of the fatty meal (time, P40.05), nor a differential effect of SFA:USFA ratio (treatment * time, P40.05) on ghrelin over 6 h. Leptin decreased in response to both HF treatments (time, Po0.001) but increased SFA content did not further inhibit hormone secretion (treatment * time, P40.05). There was no significant correlation between ghrelin or leptin and circulating insulin (P40.05). Conclusion:We conclude that HF diets may adversely effect serum leptin, although the circadian decrease may account in part for this response. Increasing dietary SFAs had no deleterious effects on leptin or total ghrelin.

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“…In experimental settings, glucose administration or food intake have been shown to decrease plasma ghrelin concentrations (7)(8)(9). Studies of the effects of ghrelin on insulin secretion have shown both stimulatory (10 -12) and inhibitory effects (13,14).…”

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confidence: 99%

Low Plasma Ghrelin Is Associated With Insulin Resistance, Hypertension, and the Prevalence of Type 2 Diabetes

et al. 2003

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Experimental studies have suggested that ghrelin plays a role in glucose homeostasis and in the regulation of blood pressure (BP). We therefore assessed the hypothesis that a low ghrelin concentration may be a risk factor for type 2 diabetes and hypertension. We also characterized the effect of the ghrelin Arg51Gln and Leu72Met mutations on ghrelin concentrations in the population-based hypertensive (n ‫؍‬ 519) and control (n ‫؍‬ 526) cohorts of our OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study. The fasting plasma ghrelin concentrations of 1,040 subjects were analyzed using the radioimmunoassay method. Insulin sensitivity was assessed using the quantitative insulin sensitivity check index (QUICKI). Ghrelin concentrations were negatively associated with fasting insulin (P < 0.001), systolic (P ‫؍‬ 0.026) and diastolic BP (P ‫؍‬ 0.018), and the prevalence of type 2 diabetes (P ‫؍‬ 0.015) and insulin resistance (P < 0.001) in the multivariate models. In the control cohort, low ghrelin was associated with hypertension (BP >140/90 mmHg) (P ‫؍‬ 0.031). The subjects with the ghrelin 51Gln allele had lower ghrelin concentrations than the Arg51Arg homozygotes (P ‫؍‬ 0.001). We conclude that low ghrelin is independently associated with type 2 diabetes, insulin concentration, insulin resistance, and elevated BP. Therefore, it might have some role in the etiology of type 2 diabetes and the regulation of BP. The ghrelin Arg51Gln mutation is associated with low plasma ghrelin concentrations. Diabetes 52:2546 -2553, 2003 G hrelin is a recently discovered peptide hormone secreted mainly from the stomach (1). It has a very potent growth hormone (GH)-releasing effect both in animal models and humans (1-3). In addition, it probably has effects independent of GH secretion (4). It is a somatotrophic orexigenic adipogenic hormone that links the regulatory systems for growth and energy balance (5). The effects of ghrelin are mediated through the GH secretagogue receptor, which is widely distributed in the body (6).The role of ghrelin in glucose and insulin metabolism has been studied actively. In experimental settings, glucose administration or food intake have been shown to decrease plasma ghrelin concentrations (7-9). Studies of the effects of ghrelin on insulin secretion have shown both stimulatory (10 -12) and inhibitory effects (13,14). In human subjects, insulin infusion has been shown to decrease ghrelin concentrations (15,16), whereas parenteral administration of insulin had no effect on ghrelin concentrations (17). On contrary, administration of insulin and leptin induced the increase of ghrelin mRNA in rats (18).Ghrelin exerts beneficial hemodynamic effects in humans by reducing cardiac afterload and increasing cardiac output (19). The vasodilatory effect is possibly mediated through a GH/IGF-I/nitric oxide-independent mechanism (20).Based on these recent studies, it appears that ghrelin might have a role in glucose and insulin metabolism and it also may influence blood pressure (BP) levels. Therefore, chang...

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Hyperglycaemia suppresses the secretion of ghrelin, a novel growth-hormone-releasing peptide: responses to the intravenous and oral administration of glucose

Cited by 166 publications

References 11 publications

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

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

Effect of high-fat meals and fatty acid saturation on postprandial levels of the hormones ghrelin and leptin in healthy men

Low Plasma Ghrelin Is Associated With Insulin Resistance, Hypertension, and the Prevalence of Type 2 Diabetes

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