Ghrelin secretion is inhibited by glucose load and insulin‐induced hypoglycaemia but unaffected by glucagon and arginine in humans

Broglio, Fabio; Gottero, Cristina; Prodam, Flavia; Destefanis, S.; Gauna, C.; Me, Elisa; Riganti, Fabrizio; Vivenza, Daniela; Rapa, Anna; Martina, V.; Arvat, Emanuela; Bona, Gianni; Lely, Aart Jan van der; Ghigo, Ezio

doi:10.1111/j.1365-2265.2004.02121.x

Cited by 71 publications

(67 citation statements)

References 65 publications

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“…In fact, oral or i.v. administration of glucose has been shown to reduce plasma ghrelin concentrations (Ariyasu et al 2002, McCowen et al 2002, Shiiya et al 2002, Nakai et al 2003, Williams et al 2003, Broglio et al 2004. Consistent with these in vivo studies, in the present study, we found that low glucose induced [Ca 2C ] i increase and ghrelin secretion in MGN3-1 cells, whereas high glucose did not.…”

Section: Discussionsupporting

confidence: 82%

Low glucose-induced ghrelin secretion is mediated by an ATP-sensitive potassium channel

Oya

Kitaguchi

Harada

et al. 2015

Journal of Endocrinology

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Ghrelin is synthesized in X/A-like cells of the gastric mucosa, which plays an important role in the regulation of energy homeostasis. Although ghrelin secretion is known to be induced by neurotransmitters or hormones or by nutrient sensing in the ghrelin-secreting cells themselves, the mechanism of ghrelin secretion is not clearly understood. In the present study, we found that changing the extracellular glucose concentration from elevated (25 mM) to optimal (10 mM) caused an increase in the intracellular Ca 2C concentration ([Ca 2C ] i ) in ghrelin-secreting mouse ghrelinoma 3-1 (MGN3-1) cells (nZ32, P!0.01), whereas changing the glucose concentration from elevated to lowered (5 or 1 mM) had little effect on [Ca 2C ] i increase. Overexpression of a closed form of an ATP-sensitive K C (K ATP ) channel mutant suppressed the 10 mM glucose-induced [Ca 2C ] i increase (nZ8, P!0.01) and exocytotic events (nZ6, P!0.01). We also found that a low concentration of a K ATP channel opener, diazoxide, with 25 mM glucose induced [Ca 2C ] i increase (nZ23, P!0.01) and ghrelin secretion (nR3, P!0.05). In contrast, the application of a low concentration of a K ATP channel blocker, tolbutamide, significantly induced [Ca 2C ] i increase (nZ15, P!0.01) and ghrelin secretion (nR3, P!0.05) under 5 mM glucose. Furthermore, the application of voltage-dependent Ca 2C channel inhibitors suppressed the 10 mM glucose-induced [Ca 2C ] i increase (nR26, P!0.01) and ghrelin secretion (nR5, P!0.05). These findings suggest that K ATP and voltage-dependent Ca 2C channels are involved in glucose-dependent ghrelin secretion in MGN3-1 cells.

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Section: Discussionsupporting

confidence: 82%

Low glucose-induced ghrelin secretion is mediated by an ATP-sensitive potassium channel

Oya

Kitaguchi

Harada

et al. 2015

Journal of Endocrinology

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“…Similarly, ghrelin is unlikely to play a major role in the control of corticotroph function since long-term treatment with synthetic GHS causes no significant increase in 24-h cortisol values (25). Moreover, the lack of any association between cortisol and ghrelin secretion during hypoglycaemia had already been reported (26,27). The fact that ghrelin does not mediate the GH and cortisol response to glucagon is also confirmed by our study that demonstrates a clear suppression of circulating ghrelin after i.m.…”

Section: Discussionsupporting

confidence: 74%

Glucagon inhibits ghrelin secretion in humans

Arafat

Otto²,

Rochlitz

et al. 2005

eur j endocrinol

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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 mg/l; peak, 14.2^2.7 mg/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.European Journal of Endocrinology 153 397-402

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“…The protocol was registered at Clinicaltrials.gov (ID NCT01919788). Nine healthy men averagely aged 22.5 (18)(19)(20)(21)(22)(23)(24)(25)(26)(27) years with an average BMI of 23.4 (21.7-26.0) kg/m 2 were recruited in this study. All had a normal physical examination.…”

Section: Methodsmentioning

confidence: 99%

Circulating acylghrelin levels are suppressed by insulin and increase in response to hypoglycemia in healthy adult volunteers

Lauritzen

Voss

Kampmann

et al. 2015

European Journal of Endocrinology

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Objective: Ghrelin has glucoregulatory and orexigenic actions, but its role in acute hypoglycemia remains uncertain. We aimed to investigate circulating levels of acylghrelin (AG) and unacylated ghrelin (UAG) in response to hyperinsulinemia and to hypoglycemia. Design: A randomized, single-blind, placebo-controlled crossover study including 3 study days was performed at a university hospital clinical research center. Methods: Nine healthy men completed 3 study days: i) saline control (CTR), ii) hyperinsulinemic euglycemia (HE) (bolus insulin 0.1 IE/kg i.v. and glucose 20% i.v. for 105 min, plasma glucose z5 mmol/l), and iii) hyperinsulinemic hypoglycemia (HH) (bolus insulin 0.1 IE/kg i.v.). Results: HH and HE suppressed AG concentrations at tZ45-60 min as compared with CTR (P!0.05). At tZ90 min, a rebound increase in AG was observed in response to HH as compared with both HE and CTR (P!0.05). UAG also decreased during HH and HE at tZ45 min (P!0.05), whereas the AG-to-UAG ratio remained unaffected. Conclusions: This study demonstrates that AG and UAG are directly suppressed by hyperinsulinemia and that AG concentrations increase after a latency of z1 h in response to hypoglycemia, suggesting a potential counterregulatory role of AG.

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Ghrelin secretion is inhibited by glucose load and insulin‐induced hypoglycaemia but unaffected by glucagon and arginine in humans

Cited by 71 publications

References 65 publications

Low glucose-induced ghrelin secretion is mediated by an ATP-sensitive potassium channel

Low glucose-induced ghrelin secretion is mediated by an ATP-sensitive potassium channel

Glucagon inhibits ghrelin secretion in humans

Circulating acylghrelin levels are suppressed by insulin and increase in response to hypoglycemia in healthy adult volunteers

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