Twenty-Four-Hour Profiles of Acylated and Total Ghrelin: Relationship with Glucose Levels and Impact of Time of Day and Sleep

Spiegel, Karine; Tasali, Esra; Leproult, Rachel; Scherberg, Neal H.; Cauter, Eve Van

doi:10.1210/jc.2010-1978

Cited by 92 publications

(83 citation statements)

References 23 publications

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“…AG levels may be an important predictor of the glucose control under physiological conditions [101]. Ghrelin clearly stimulated insulin-mediated glucose disposal, an observation that was consistent with enhanced 2-deoxy-d-[3H]glucose (2DG) uptake in muscle and adipose tissue during hyperinsulinemia in ghrelin-treated animals [102].…”

Section: Effects Of Ghrelin and Hexarelin On Insulin Secretion And Glmentioning

confidence: 57%

Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases

et al. 2015

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Ghrelin and its synthetic analog hexarelin are specific ligands of growth hormone secretagogue (GHS) receptor. GHS have strong growth hormone-releasing effect and other neuroendocrine activities such as stimulatory effects on prolactin and adrenocorticotropic hormone secretion. Recently, several studies have reported other beneficial functions of GHS that are independent of GH. Ghrelin and hexarelin, for examples, have been shown to exert GH-independent cardiovascular activity. Hexarelin has been reported to regulate peroxisome proliferator-activated receptor gamma (PPAR-γ) in macrophages and adipocytes. PPAR-γ is an important regulator of adipogenesis, lipid metabolism, and insulin sensitization. Ghrelin also shows protective effects on beta cells against lipotoxicity through activation of phosphatidylinositol-3 kinase/protein kinase B, c-Jun N-terminal kinase ( JNK) inhibition, and nuclear exclusion of forkhead box protein O1. Acylated ghrelin (AG) and unacylated ghrelin (UAG) administration reduces glucose levels and increases insulinproducing beta cell number, and insulin secretion in pancreatectomized rats and in newborn rats treated with streptozotocin, suggesting a possible role of GHS in pancreatic regeneration. Therefore, the discovery of GHS has opened many new perspectives in endocrine, metabolic, and cardiovascular research areas, suggesting the possible therapeutic application in diabetes and diabetic complications especially diabetic cardiomyopathy. Here, we review the physiological roles of ghrelin and hexarelin in the protection and regeneration of beta cells and their roles in the regulation of insulin release, glucose, and fat metabolism and present their potential therapeutic effects in the treatment of diabetes and diabetic-associated heart diseases. Disciplines Medicine and Health Sciences Publication DetailsMosa, R., Zhang, Z., Shao, R., Deng, C., Chen, J. & Chen, C. (2015). Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases. Endocrine, 49 (2) AbstractGhrelin and its synthetic analog hexarelin are specific ligands of growth hormone secretagogue (GHS) receptor. GHS have strong growth hormone-releasing effect and other neuroendocrine activities such as stimulatory effects on prolactin and adrenocorticotropic hormone secretion. Recently, several studies have reported other beneficial functions of GHS that are independent of GH. Ghrelin and hexarelin, for examples, have been shown to exert GH-independent cardiovascular activity. Hexarelin has been reported to regulate peroxisome proliferator-activated receptor gamma (PPAR-γ) in macrophages and adipocytes. PPAR-γ is an important regulator of adipogenesis, lipid metabolism, and insulin sensitization. Ghrelin also shows protective effects on beta cells against lipotoxicity through activation of phosphatidylinositol-3 kinase/protein kinase B, c-Jun N-terminal kinase (JNK) inhibition, and nuclear exclusion of forkhead box protein O1. Acylated ghrelin (AG) and unacylated ghrelin (UAG) administration redu...

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Section: Effects Of Ghrelin and Hexarelin On Insulin Secretion And Glmentioning

confidence: 57%

Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases

et al. 2015

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“…This may have led to an underestimation of the effects of hyperglycemia in relation to our observed changes in gut hormones. Finally, although acylated ghrelin is considered active, we have found previously that oral glucose induces similar plasma responses of total and acylated ghrelin, indicating that total ghrelin provides a surrogate marker of secretion of the acylated form (19,39).…”

Section: E229mentioning

confidence: 75%

Hyperglycemia abolishes meal-induced satiety by a dysregulation of ghrelin and peptide YY_3–36 in healthy overweight/obese humans

Knudsen

Karstoft

Solomon

2014

American Journal of Physiology-Endocrinology and Metabolism

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Satiety and satiety-regulating gut hormone levels are abnormal in hyperglycemic individuals. We aimed to determine whether these abnormalities are secondary to hyperglycemia. Ten healthy overweight/obese subjects (age: 56 ± 3 yr; BMI: 30.3 ± 1.2 kg/m(2)) received three equicaloric meals at t = 0, 4, and 8 h in the absence (control trial) and presence of experimental hyperglycemia (hyperglycemia trial; 5.4 mM above basal). Circulating levels of glucose, insulin, ghrelin, and peptide YY (PYY)3-36 and visual analog scale ratings of satiety were measured throughout each trial. In the control trial, glucose, insulin, PYY3-36, and the feeling of fullness were increased in the postprandial periods, whereas ghrelin was decreased. In the hyperglycemia trial, in which plasma glucose was increased to 11.2 ± 0.1 mmol/l, postprandial meal responses (AUC: 0-2, 4-6, and 8-10 h) of PYY3-36 were lower (meal 1, P < 0.0001; meal 2, P < 0.001; meal 3, P < 0.05), whereas insulin (meal 1, P < 0.01; meal 2, P < 0.001; meal 3, P < 0.05) and ghrelin (meal 1, P < 0.05; meal 2, P > 0.05; meal 3, P > 0.05) were higher compared with the control trial. Furthermore, the incremental (Δ0-0.5, 4-4.5, and 8-8.5 h) ghrelin response to the first and third meals was higher in the hyperglycemia trial in contrast to control (Δ: 2.3 ± 8.0, P = 0.05; Δ: 14.4 ± 2.5, P < 0.05). Also, meal-induced fullness was prevented (meal 1, P = 0.06; meal 2, P = 0.01; meal 3, P = 0.08) by experimental hyperglycemia. Furthermore, trends in ghrelin, PYY3-36, and fullness were described by different polynomial functions between the trials. In conclusion, hyperglycemia abolishes meal-induced satiety and dysregulates postprandial responses of the gut hormones PYY3-36 and ghrelin in overweight/obese healthy humans.

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“…Lastly, the measurement of circulating hormones for a 24-hour period allowed us to account for changes in response to all three meals as well as any non-food related events that may have occurred in the profiles of these hormones. For example, the nocturnal event of ghrelin may respond to changes in sleep patterns [35, 36] and plays a role in the regulation of other hormones like cortisol and growth hormone [40]. Additionally, ghrelin is secreted from the stomach [13] whereas PYY is mainly secreted from L cells in the ileum [1].…”

Section: Discussionmentioning

confidence: 99%

The impact of weight loss on the 24-h profile of circulating peptide YY and its association with 24-h ghrelin in normal weight premenopausal women

et al. 2013

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Peptide YY (PYY) and ghrelin exhibit a reciprocal association and antagonistic physiological effects in the peripheral circulation. Research has yet to clarify the effect of weight loss on the 24h profile of PYY or its association to 24h ghrelin. We sought to determine if diet- and exercise-induced weight loss affects the 24h profile of PYY and its association with 24h ghrelin in normal weight, premenopausal women. Participants (n=13) were assessed at baseline (BL) and after a 3-month diet and exercise intervention (Post). Blood samples obtained q10 min for 24h were assayed for total PYY and total ghrelin q60 min from 0800–1000h and 2000–0800h and q20 min from 1000–2000h. The ghrelin/PYY ratio was used as an index of hormonal exposure. Statistical analyses included paired t-tests and linear mixed effects modeling. Body weight (−1.85±0.67kg; p=0.02), and body fat (−2.53±0.83%; p=0.01) decreased from BL to post. Ghrelin AUC (5252±2177pg/ml/24hr; p=0.03), 24h mean (216±90pg/ml; p=0.03) and peak (300±134pg/ml; p=0.047) increased from BL to post. No change occurred in PYY AUC (88.2±163.7pg/ml; p=0.60), 24h mean (4.8±6.9pg/ml; p=0.50) or peak (3.6±6.4pg/ml; p=0.58). The 24h association between PYY and ghrelin at baseline (p=0.04) was weakened at post (p=0.14); however, the ghrelin/PYY lunch ratio increased (p=0.01) indicating the potential for ghrelin predominance over PYY in the circulation. PYY and ghrelin are reciprocally associated during a period of weight stability, but not following weight loss. An “uncoupling” may have occurred, particularly at lunch, due to factors that modulate ghrelin in response to weight loss.

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Twenty-Four-Hour Profiles of Acylated and Total Ghrelin: Relationship with Glucose Levels and Impact of Time of Day and Sleep

Cited by 92 publications

References 23 publications

Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases

Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases

Hyperglycemia abolishes meal-induced satiety by a dysregulation of ghrelin and peptide YY_3–36 in healthy overweight/obese humans

The impact of weight loss on the 24-h profile of circulating peptide YY and its association with 24-h ghrelin in normal weight premenopausal women

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Twenty-Four-Hour Profiles of Acylated and Total Ghrelin: Relationship with Glucose Levels and Impact of Time of Day and Sleep

Cited by 92 publications

References 23 publications

Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases

Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases

Hyperglycemia abolishes meal-induced satiety by a dysregulation of ghrelin and peptide YY3–36 in healthy overweight/obese humans

The impact of weight loss on the 24-h profile of circulating peptide YY and its association with 24-h ghrelin in normal weight premenopausal women

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Hyperglycemia abolishes meal-induced satiety by a dysregulation of ghrelin and peptide YY_3–36 in healthy overweight/obese humans