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Arvat, Emanuela; Maccagno, B.; Ramunni, J.; Giordano, Roberta; DiVito, Lidia; Broglio, Fabio; Maccario, Mauro; Camanni, F.; Ghigo, Ezio

doi:10.1023/a:1011451710004

Cited by 17 publications

(4 citation statements)

References 19 publications

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“…Josefsberg et al [33] observed a GH response to iv glucagon that was similar to the one observed following iv arginine. In contrast, three studies performed in adults [35, 36] and children [37] observed a poor or absent GH response following iv administration of 1 mg glucagon, contrasting with a good GH response following im or sc administration of 1 mg glucagon despite similar changes in blood glucose. Cortisol response was similarly affected by the route of administration of glucagon, at least in adults [36].…”

Section: Discussionmentioning

confidence: 98%

“…In contrast, three studies performed in adults [35, 36] and children [37] observed a poor or absent GH response following iv administration of 1 mg glucagon, contrasting with a good GH response following im or sc administration of 1 mg glucagon despite similar changes in blood glucose. Cortisol response was similarly affected by the route of administration of glucagon, at least in adults [36]. In a recent review, Sizonenko et al [13] suggested that the route of administration could influence the timing of the GH response.…”

Section: Discussionmentioning

confidence: 98%

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Ghrelin Is Suppressed by Glucagon and Does Not Mediate Glucagon-Related Growth Hormone Release

Hirsh

Heinrichs²,

Leenders³

et al. 2005

Horm Res Paediatr

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Background:Glucagon stimulation is routinely used as a provocative test to assess growth hormone (GH) sufficiency in pediatrics. Ghrelin also markedly stimulates GH secretion. Because glucagon stimulates the promoter of the ghrelin gene in vitro as well as ghrelin secretion by the perfused rat stomach, we sought todetermine whether ghrelin mediates glucagon-induced GH secretion. Methods: We compared ghrelin, GH, insulin and glucose responses following administration of 0.03 mg/kg intravenously (iv; max. 1 mg) and 0.1 mg/kg intramuscularly (im; max. 2 mg) of glucagon in two groups (n = 10–11/group) of GH-sufficient children. We also measured ghrelin before and 6 min after iv administration of 1 mg glucagon in 21 adult subjects. Results: In children, glucagon caused a 26% decrease in ghrelin and a 72% increase in glucose concentrations that were independent of the dose or administration route of glucagon. In contrast, the insulin response was 2–3 times higher following administration of 0.1 mg/kg im compared to 0.03 mg/kg of glucagon iv. There was a significant correlation between the maximum decrease in ghrelin and increases in glucose (p = 0.03) but not in insulin. There was a significant correlation between ghrelin and GH area under the curve after controlling for the dose of glucagon (p = 0.03) but not for the maximum increase in glucose.In normal adults, glucagon administration caused a 7% decrease in ghrelin concentrations after 6 min (p = 0.0002). Conclusion: Ghrelin does not play a causal role in the GH response to pharmacological glucagon administration, which suppresses ghrelin levels starting a few minutes after injection.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

Ghrelin Is Suppressed by Glucagon and Does Not Mediate Glucagon-Related Growth Hormone Release

Hirsh

Heinrichs²,

Leenders³

et al. 2005

Horm Res Paediatr

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“…The result is that tumor cells mobilize body stores in anabolic and glycolytic conditions, to build the tumor mass using body stores, the metabolic rewiring linked to the blockade of PK and PDH in tumor cells and in body stores is schematized in Figure 1B, in tumor cells PK and PDH are inactivated via PKA signals, while the other tumor enzymes are boosted via PKB. Moreover, the release of glucagon acts on central neurons releasing corticotropin-releasing hormone (CRH), which increases ACTH release [16]. The latter, triggers the release of glucocorticoids (cortisol) from the adrenal cortex that binds to steroid receptors in muscles inducing proteolysis.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the central action of glucagon [16] increases growth hormone release and then IGF, which boosts the insulin effect. Somatostatin release from delta cells cannot attenuate Growth Hormone-IGF actions since the increase of epinephrine, resulting from the lower GABA released, blocks the delta cells [15], epinephrine instead does the job for GABA.…”

Section: Introductionmentioning

confidence: 99%

A possible primary cause of cancer: deficient cellular interactions in endocrine pancreas

Israël¹

2012

Mol Cancer

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BackgroundCancer is a devastating type of disease. New and innovative ways to tackle cancers that have so far proved refractive to conventional therapies is urgently needed. It is becoming increasingly clear that, in addition to conventional therapeutics targeting by small molecules, that tumor cell metabolism presents new opportunities to target selectively specific cancer cell populations. Metabolic defects in cancer cells can be manifested in many ways that might not be readily apparent, such as altering epigenetic gene regulation for example.The complex rewiring of metabolic pathways gives tumor cells a special advantage over differentiated cells, since they deplete body stores as fuel for their growth and proliferation. Tumor metabolism looks simpler when we consider that some enzymatic switches are in a neoglucogenic direction thereby depleting body stores. However, these pathways may be inadequately switched on by catabolic hormones (glucagon, epinephrine and cortisol) in a specific situation where anabolism is activated by, for example insulin released from beta pancreatic cells or IGF, inducing mitosis and synthesis that are powered by glucose catabolism. Such a hybrid metabolic situation would be reached if a pancreatic beta cell mechanism, mediated by GABA, failed to silence neighboring alpha cells and delta cells. The inhibitory transmitter GABA hyperpolarizes alpha and delta cells via their GABA A receptors, and blocks the release of glucagon and somatostatin. Alternatively, an anomaly of alpha cell channels, would lead to a similar situation. Whatever is the alteration, anabolism fails to silence catabolism and enzymatic switches controlled by kinases and phosphatases adopt an inadequate direction, leading to a hybrid metabolic rewiring found in cancer. It is daring to formulate such a hypothesis as this. However, it is quite possible that the starting point in cancer is an alteration of the endocrine pancreas, suppressing the mechanism by which beta cells silence the neighboring alpha and delta cells, with GABA and Zn2+.

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Glucagon administration elicits blunted GH but exaggerated ACTH response in obesity

Tassone

Grottoli

Rossetto

et al. 2002

J Endocrinol Invest

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Reduction in both spontaneous and stimulated GH secretion in obesity has been clearly demonstrated. Mild hyperactivity of hypothalamus-pituitary-adrenal (HPA) axis has been also reported. Glucagon, at least after im administration, induces clear increase in either GH or ACTH and F levels but its effect on somatotroph and corticotroph secretion in obesity has never been studied. In 7 patients with abdominal obesity (OB, aged 24-42 yr, BMI: 29.1-43.9 kg/m2, waist/hip ratio [WHR]: 0.86-1.00) we studied the GH, ACTH and F responses to the im administration of glucagon (0.017 mg/kg at 0 min). The results in OB were compared with those in a group of 6 age-matched controls normal subjects (Ns aged 26-32 yr, BMI 19.7-22.5 kg/m2). In Ns glucagon administration induced clear increase in GH (peak vs baseline, mean+/-SE: 11.6+/-3.4 vs 3.3+/-0.7 microg/l, p<0.02), and ACTH (52.9+/-15.2 vs 19.0+/-1.5 pg/ml, p<0.02) levels which peaked at +150 and +165 min, respectively. Increase in F levels (222.3+/-23.8 vs 158.3+/-7.0 ng/ml, p<0.05) was also recorded but peaked at +180 min. In OB glucagon administration induced GH response (7.4+/-2.3 vs 0.8+/-0.6 microg/l) lower (p<0.05) than that recorded in Ns; when the GH responses were evaluated by co-variance analysis, a significant difference between the 2 groups was recorded in term of peaks but not of AUCs. On the other hand, the ACTH response to glucagon in OB was higher than that in Ns (11452.6+/-2447.7 vs 4892.2+/-719.4 pg/ml x min, p<0.05). The F response to glucagon in OB and Ns was, however, similar (24057.9+/-4109.1 vs 29835.9+/-1566.0 ng/ml x min). In conclusion, this study demonstrates that in obese patients the im administration of glucagon elicits blunted GH response but exaggerated ACTH increase which is uncoupled with the adrenal response. These findings agree with the existence of concomitant GH insufficiency and altered corticotroph function in obesity.

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Cited by 17 publications

References 19 publications

Ghrelin Is Suppressed by Glucagon and Does Not Mediate Glucagon-Related Growth Hormone Release

Ghrelin Is Suppressed by Glucagon and Does Not Mediate Glucagon-Related Growth Hormone Release

A possible primary cause of cancer: deficient cellular interactions in endocrine pancreas

Glucagon administration elicits blunted GH but exaggerated ACTH response in obesity

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