Inhibition of Hypoglycemia-Induced Cortisol Secretion by the Serotonin Antagonist Cyproheptadine

Plonk, James W.; Bivens, Carl H.; Feldman, Jerome M.

doi:10.1210/jcem-38-5-836

Cited by 103 publications

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“…Since the same dose of insulin was administered and both the basal level and the nadir of blood glucose were quite similar in all 5 insulin tolerance tests, it is unlikely that the difference in the responsiveness of GH and cortisol were closely related to the degree of hypoglycemia or the dose of insulin administered. On the other hand, it is generally accepted that hypoglycemic stress causes a stimulation of both GH and ACTH secretion as a result of the release of respective hypothalamic releasing factors from the hypothalamus (Bivens et al, 1973;Plonk et al, 1974;Aizawa et al, 1981;Karteszi et al, 1982). Therefore, the release of both GH-releasing factor and cortcotropin-releasing factor from the hypothalamus might be impaired in this patient.…”

Section: Discussionmentioning

confidence: 81%

Unresponsiveness of GH and cortisol to insulin-hypoglycemia in a patient with sub-total pancreatectomy.

et al. 1983

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Responses of plasma growth hormone (GH) and cortisol to insulin-induced hypoglycemia were repeatedly examined during a therapy of diabetes mellitus in a sub-totally pancreatectomized patient. During a mild control period of diabetes mellitus without any hypoglycemic attacks, insulin-induced hypoglycemia evoked a remarkable increase in plasma GH as well as cortisol while neither GH nor cortisol responded to insulin hypoglycemia during the strict control period with frequent episodesof hypoglycemia.On the other hand, plasma GH and cortisol responses to all other endocrinological stimuli were normal.The mechanism of such impaired hormone secretion during the strict control period of diabetes mellitus in this patientremains unclear.

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Section: Discussionmentioning

confidence: 81%

Unresponsiveness of GH and cortisol to insulin-hypoglycemia in a patient with sub-total pancreatectomy.

et al. 1983

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“…The hypothesis is supported by the finding that cyproheptadine reduced arginineinduced glucagon release. In addition, cyproheptadine is known to diminish the secretion of human growth hormone and cortisol [9,10,11]. Thus a general property to inhibit hormone release may be attributed to the agent.…”

Section: Discussionmentioning

confidence: 99%

“…Acute hyperglycemia after single injections of cyproheptadine, accompanied by a decrease of plasma insulin, was observed in the rat [5] and in the Syrian hamster [6]. In addition, in vitro experiments using the perfused rat pancreas [5], isolated islets [7,8], and pieces of Syrian hamster pancreas [6] revealed the inhibitory effect of cyproheptadine on insulin release.To gain further insight into this inhibition we investigated the effects of cyproheptadine on insulin release as caused by various stimulators and effectors.Cyproheptadine has also been reported to inhibit growth hormone (HGH) secretion [9,10] and cortisol release [11], suggesting that cyproheptadine has a general inhibitory effect on hormone release. Thus we studied the effects of cyproheptadine on the arginineinduced glucagon release by the perfused rat pancreas.…”

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Inhibition of insulin and glucagon release from the perfused rat pancreas by cyproheptadine (Periactinol�, Nuran�)

et al. 1976

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Summary. The tricyclic compound cyproheptadine (Feriactinol | Nuran | inhibited glucose-induced insulin release from the peffused rat pancreas. Tolbutamide-stimulated insulin release was significantly reduced in the presence and completely suppressed in the absence of a substimulatory glucose concentration (5 mM). Arginine produced a slow rise of insulin release, which was completely abolished by cyproheptadine. Furthermore the biphasic glucagon release due to the stimulus was inhibited. Oxidation of ~4C-glucose in isolated islets was unaltered in the presence of cyproheptadine, and pyruvate added to the perfusion medium failed to reverse the inhibitory effect on glucose induced insulin release, indicating that impaired glucose metabolism is not responsible for the inhibition. In addition, the inhibition remained unchanged when phentolamine was present, suggesting that the effect is not mediated by inhibitory adrenergic alpha receptors. Theophylline, in contrast, partly overcame the inhibition. When the calcium concentration of the medium was enhanced, the inhibitory effect of cyproheptadine was still visible, although the relative inhibition had become smaller. The results suggest that cyproheptadine blocks insulin release by affecting a fundamental step of the stimulus-secretion coupling common to peptide hormones. A participation of a calcium-antagonizing effect in the inhibition is discussed.Key words: Insulin release, glucagon release, cyproheptadine, tolbutamide, arginine, theophylline, calcium, peffused rat pancreas. The antihistaminic-antiserotonin compound cyproheptadine [1] has been reported to produce selective B-cell abnormalities, glucose intolerance, and depletion of pancreatic insulin in rats [2, 3, 4] when chronically administered. Acute hyperglycemia after single injections of cyproheptadine, accompanied by a decrease of plasma insulin, was observed in the rat [5] and in the Syrian hamster [6]. In addition, in vitro experiments using the perfused rat pancreas [5], isolated islets [7,8], and pieces of Syrian hamster pancreas [6] revealed the inhibitory effect of cyproheptadine on insulin release.To gain further insight into this inhibition we investigated the effects of cyproheptadine on insulin release as caused by various stimulators and effectors.Cyproheptadine has also been reported to inhibit growth hormone (HGH) secretion [9,10] and cortisol release [11], suggesting that cyproheptadine has a general inhibitory effect on hormone release. Thus we studied the effects of cyproheptadine on the arginineinduced glucagon release by the perfused rat pancreas. Materials and Methods ChemicalsCyproheptadine-hydrochloride (Sharp and Dohme, Miinchen), Trasylol | (Farbwerke Bayer AG, Wuppertal-Elberfeld), tolbutamide (Hoechst AG, Frankfurt) and dextran (Knoll AG, Ludwigshafen) were obtained as gifts. Bovine albumin, pentobarbital and arginine were purchased from Serva, Heidelberg, Phentolamine (Regitin | ampoules) from Ciba AG, 1-125 labelled insulin and glucagon (50-60% immunoreactive glucagon) from Farb...

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“…The key hormonal switches involved, adrenal glucocorticoids [5] and catecholamines [6], are secreted as a hypoglycemic response. These hormones are also secreted in response to fasting [7].…”

Section: ) Entering the Fat-burning Statementioning

confidence: 99%

The Dangers of Fat Metabolism and PUFA: Why You Don’t Want to be a Fat Burner

Mamounis¹

2017

jevohealth

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Inhibition of Hypoglycemia-Induced Cortisol Secretion by the Serotonin Antagonist Cyproheptadine

Cited by 103 publications

References 0 publications

Unresponsiveness of GH and cortisol to insulin-hypoglycemia in a patient with sub-total pancreatectomy.

Unresponsiveness of GH and cortisol to insulin-hypoglycemia in a patient with sub-total pancreatectomy.

Inhibition of insulin and glucagon release from the perfused rat pancreas by cyproheptadine (Periactinol�, Nuran�)

The Dangers of Fat Metabolism and PUFA: Why You Don’t Want to be a Fat Burner

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