Metabolic effects of graded glucagon infusions in man: Inhibition of glucagon, insulin, and somatostatin response to arginine

Pontiroli, A. E.; Perfetti, M. G.; Andreotti, A. C.; Fattor, Bruno; Monti, Lucilla D.; Pozza, G.

doi:10.1016/0026-0495(93)90120-d

Cited by 5 publications

(2 citation statements)

References 48 publications

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“…The mechanisms underlying glucagon-induced GH secretion are poorly understood. A decrease in somatostatin secretion [29] or in free fatty acid concentrations [29, 30] have been proposed as potential explanations. Sustained hyperglycemia [31] and absence of hyperglycemic response to glucagon following prolonged fasting [32] obliterate the GH response to glucagon, suggesting that hyperglycemia followed by a decrease in blood sugar towards normal values is necessary to elicit GH response.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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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“…Because of the complexity of homeostatic networks, mathematical models are often required to quantify the loss or erosion of reciprocal linkages among metabolic signals. Indeed, pathophysiological studies suggest that multiple regulatory defects may exist in type 2 diabetes mellitus (DM) and possibly in impaired fasting glycemia (IFG) (8,18,20,25,30). Although computer-assisted simulations have shed light on plausible homeostatic control mechanisms (7,23,27,28,34), analytic estimation methods are needed to quantify the type and degree of impairment in pathophysiology.…”

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confidence: 99%

Logistic model of glucose-regulated C-peptide secretion: hysteresis pathway disruption in impaired fasting glycemia

Keenan

Basu

Liu³

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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The present analysis tests the hypothesis that quantifiable disruption of the glucose-stimulated insulin-secretion dose-response pathway mediates impaired fasting glycemia (IFG) and type 2 diabetes mellitus (DM). To this end, adults with normal and impaired fasting glycemia (NFG, n = 30), IFG (n = 32), and DM (n = 14) were given a mixed meal containing 75 g glucose. C-peptide and glucose were measured over 4 h, 13 times in NFG and IFG and 16 times in DM (age range 50-57 yr, body mass index 28-32 kg/m(2)). Wavelet-based deconvolution analysis was used to estimate time-varying C-peptide secretion rates. Logistic dose-response functions were constructed analytically of the sensitivity, potency, and efficacy (in the pharmacological sense of slope, one-half maximal stimulation, and maximal effect) of glucose's stimulation of prehepatic insulin (C-peptide) secretion. A hysteresis changepoint time, demarcating unequal glucose potencies for onset and recovery pathways, was estimated simultaneously. According to this methodology, NFG subjects exhibited distinct onset and recovery potencies of glucose in stimulating C-peptide secretion (6.5 and 8.5 mM), thereby defining in vivo hysteresis (potency shift -2.0 mM). IFG patients manifested reduced glucose onset potency (8.6 mM), and diminished C-peptide hysteretic shift (-0.80 mM). DM patients had markedly decreased glucose potency (18.8 mM), reversal of C-peptide's hysteretic shift (+4.5 mM), and 30% lower C-peptide sensitivity to glucose stimulation. From these data, we conclude that a dynamic dose-response model of glucose-dependent control of C-peptide secretion can identify disruption of in vivo hysteresis in patients with IFG and DM. Pathway-defined analytic models of this kind may aid in the search for prediabetes biomarkers.

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About the effects of glucagon on growth hormone release

Pontiroli

1995

J Endocrinol Invest

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Metabolic effects of graded glucagon infusions in man: Inhibition of glucagon, insulin, and somatostatin response to arginine

Cited by 5 publications

References 48 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

Logistic model of glucose-regulated C-peptide secretion: hysteresis pathway disruption in impaired fasting glycemia

About the effects of glucagon on growth hormone release

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