Thyroxine treatment and insulin secretion in the rat

Lenzen, Sigurd; Panten, U.; Hasselblatt, A.

doi:10.1007/bf00422818

Cited by 38 publications

(19 citation statements)

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“…given i.p. for 5 consecutive days) (Sigma, St. Louis, Mo., USA) dissolved in 0.9% NaCl solution [4,9]. Alternatively, in time course studies, L-thyroxine (20 mg/kg b.wt.)…”

Section: Methodsmentioning

confidence: 99%

Thyroxine induces pancreatic beta-cell apoptosis in rats

2002

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Aims/hypothesis. Thyroid hormones reduce glucose tolerance in animals and humans. This effect is accompanied by a reduction in the beta-cell volume of the pancreas. Methods. We studied the underlying mechanism using terminal UTP nick end labelling (TUNEL) and caspase-3 to analyse apoptosis and BrdU labelling of betacell proliferation. Results. The reason for the reduction of the beta-cell volume of the pancreas after thyroxine treatment is apparently an increased rate of beta-cell apoptosis by an increase of TUNEL and caspase-3 positive rat beta cells. In parallel, thyroxine treatment increased the rate of apoptosis in rat pancreatic ductal cells which are considered to contribute to the pool of stem cells from which insulin-producing beta cells originate. The effects of thyroid hormone treatment are reversible through an increase of the beta-cell replication rate when thyroxine is withdrawn as documented by an increase of the BrdU labelling index. Conclusion/interpretation. An increased rate of betacell death due to apoptosis causes a decrease of insulin content and glucose-induced insulin secretion from the pancreas in hyperthyroidism. The resulting reduction of beta cells in the pancreas can provide an explanation for the decrease of glucose tolerance in hyperthyroidism. [Diabetologia (2002) underlying pancreatic beta-cell loss is not known [2]. The prohormone thyroxine is deiodinated to triiodothyronine in many tissues [6] including pancreatic islets [7]. Triiodothyronine mediates its effects through binding to thyroid hormone nuclear receptors [6]. As thyroid hormones play a major role in apoptotic tissue remodelling [8] we studied whether the effects of thyroxine on the endocrine pancreas might be caused by an increased rate of apoptosis of the beta cells in the islets of Langerhans. Materials and methodsExperimental design. Experimental hyperthyroidism accompanied by mild hyperglycaemia (5.5 ± 0.1 vs 4.7 ± 0.1 mmol/l in control rats; p < 0.05, Student's t test) and mild hyperinsulinaemia (0.59 ± 0.11 vs. 0.40 ± 0.04 ng/ml in control rats; p < 0.05, Student's t test) was induced in Lewis rats (190-230 g) through treatment with L-thyroxine (600 µg/kg Thyroid hormones have a multitude of metabolic effects [1] and act as insulin antagonists [2]. Hyperthyroidism induces glucose intolerance in animals and humans [2,3]. In particularly prone individuals, hyperthyroidism can induce a so-called "thyroid diabetes" [2]. Thyroxine treatment causes a state of experimental hyperthyroidism and reduces the pancreatic insulin content and glucose-induced insulin secretion [4,5]. This is accompanied by a reduction in the beta-cell volume of the pancreas [5]. However, the mechanism

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“…given i.p. for 5 consecutive days) (Sigma, St. Louis, Mo., USA) dissolved in 0.9% NaCl solution [4,9]. Alternatively, in time course studies, L-thyroxine (20 mg/kg b.wt.)…”

Section: Methodsmentioning

confidence: 99%

Thyroxine induces pancreatic beta-cell apoptosis in rats

2002

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“…In addition, T 3 is a protective factor against STZ-induced diabetes (Verga Falzacappa et al, 2011), and thyroid hormone receptor α-1 expression occurs in pancreatic islets (Zinke et al, 2003). In contrast, systemic hyperthyroidism can decrease glucose tolerance and the insulin secretory capacity of β-cells (Lenzen et al, 1975;Ximenes et al, 2007). In rats, T 4 can induce apoptosis in pancreatic β-cells (Jörns et al, 2002).…”

Section: Discussionmentioning

confidence: 94%

“…Thyroid hormone improves insulin resistance by acting on brown adipose tissue (Skarulis et al, 2010) and modulates hepatic glucose production (Klieverik et al, 2009). In contrast, systemic hyperthyroidism decreases glucose tolerance and β-cell insulin secretory capacity (Lenzen et al, 1975;Ximenes et al, 2007). Reduced thyroid hormone signaling in pancreatic β-cells is important for normal islet function and glucose homeostasis (Medina et al, 2011).…”

Section: Introductionmentioning

confidence: 96%

Glucagon-like peptide-1 stimulates type 3 iodothyronine deiodinase expression in a mouse insulinoma cell line

et al. 2014

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“…The inhibitory effects of iodoacetate [20] and thyroxine treatment [21] on insulin release can almost completely be reversed by pyruvate. Since pyruvate may serve as a source of metabolic energy which is utilized independently from glycolysis, these findings with enhanced calcium concentration of the medium in order to reverse the inhibition.…”

Section: Discussionmentioning

confidence: 97%

“…were supposed to reflect a specific interference with glucose metabolism [21]. Infused together with glucose and cyproheptadine, pyruvate failed to restore the normal secretory response.…”

Section: Discussionmentioning

confidence: 97%

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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Thyroxine treatment and insulin secretion in the rat

Cited by 38 publications

References 17 publications

Thyroxine induces pancreatic beta-cell apoptosis in rats

Thyroxine induces pancreatic beta-cell apoptosis in rats

Glucagon-like peptide-1 stimulates type 3 iodothyronine deiodinase expression in a mouse insulinoma cell line

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

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