Melatonin suppresses hyperglycemia caused by intracerebroventricular injection of 2-deoxy-d-glucose in rats

Shima, Takaki; Chun, Soo-Jin; Niijima, Akira; Bizot-Espiard, Jean-Guy; Guardiola‐Lemaître, B.; Hosokawa, Mami; Nonomura, Katsuya

doi:10.1016/s0304-3940(97)00257-7

Cited by 30 publications

(19 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previously, we have reported the ability of melatonin to control gluconeogenesis in experiments that showed that surgical ablation of the pineal gland reduced glucose clearance after pyruvate load (23). Corroborating our present hypothesis that melatonin may suppress gluconeogenesis due to its action in the central nervous system, a previous study demonstrated that intracranial rather than intraperitoneal injections of melatonin effectively suppressed the hyperglycemic response to the intracranial injection of 2-deoxy-D-glucose (35). The experimental finding showing that melatonin injected directly in the MBH also increased glucose clearance after pyruvate load further corroborates the hypothesis that this hormone might suppress gluconeogenesis due to a primary action in the hypothalamus.…”

Section: Discussionsupporting

confidence: 77%

Melatonin acts through MT1/MT2 receptors to activate hypothalamic Akt and suppress hepatic gluconeogenesis in rats

Faria

Kinote

Ignácio-Souza

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Melatonin can contribute to glucose homeostasis either by decreasing gluconeogenesis or by counteracting insulin resistance in distinct models of obesity. However, the precise mechanism through which melatonin controls glucose homeostasis is not completely understood. Male Wistar rats were administered an intracerebroventricular (icv) injection of melatonin and one of following: an icv injection of a phosphatidylinositol 3-kinase (PI3K) inhibitor, an icv injection of a melatonin receptor (MT) antagonist, or an intraperitoneal (ip) injection of a muscarinic receptor antagonist. Anesthetized rats were subjected to pyruvate tolerance test to estimate in vivo glucose clearance after pyruvate load and in situ liver perfusion to assess hepatic gluconeogenesis. The hypothalamus was removed to determine Akt phosphorylation. Melatonin injections in the central nervous system suppressed hepatic gluconeogenesis and increased hypothalamic Akt phosphorylation. These effects of melatonin were suppressed either by icv injections of PI3K inhibitors and MT antagonists and by ip injection of a muscarinic receptor antagonist. We conclude that melatonin activates hypothalamus-liver communication that may contribute to circadian adjustments of gluconeogenesis. These data further suggest a physiopathological relationship between the circadian disruptions in metabolism and reduced levels of melatonin found in type 2 diabetes patients. melatonin; gluconeogenesis; melatonin receptors; liver MELATONIN (5-methoxy-N-acetyltryptamine) is produced and secreted by the pineal gland in a circadian fashion, with peak levels during the dark phase of the light-dark cycle. The canonical function of melatonin is to transmit environmental information (i.e., the length of the dark period) to the living organism, thereby synchronizing the circadian clock in the hypothalamic suprachiasmatic nucleus (22). In vivo and in vitro experiments have demonstrated that melatonin also plays a role in energy homeostasis by regulating body mass and adiposity and leptin expression by adipocytes (1, 40). Glucose homeostasis is also altered by the absence of melatonin in such a way that pinealectomized rats display glucose intolerance and desynchronized circadian pattern of gluconeogenesis, hallmarked by increased nighttime glucose levels (17,18,23). Moreover, chronic melatonin administration has been shown to improve glucose homeostasis not only in pinealectomized rats but also in rats rendered insulin resistant by diet manipulation (16,33,34).Although it has been demonstrated that melatonin stimulates glucose uptake in adipocytes and skeletal muscle cells in vitro (10, 19), the precise mechanism by which this hormone reduces whole body glucose intolerance has not been determined precisely. In mammals, the effects of melatonin are mediated in part by specific high-affinity G protein-coupled receptors known as melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2) (31). We have demonstrated previously that melatonin acts locally in the hypothalamus to activate the p...

show abstract

Section: Discussionsupporting

confidence: 77%

Melatonin acts through MT1/MT2 receptors to activate hypothalamic Akt and suppress hepatic gluconeogenesis in rats

Faria

Kinote

Ignácio-Souza

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…Bailey et al (1974) confirmed the inhibition of glucose-induced secretion of insulin by MEL. Depressive effect of intracerebrally administered MEL on hyperglycaemia induced by 2-deoxyglucose has been proved (Shima et al 1997). MEL increased the concentration of serum glucose and content of glycogen in the myocardium of NTB animals in our experiment; this should be connected with a reduced effect of insulin on the periphery.…”

Section: Discussionsupporting

confidence: 55%

Chemoprevention of N-Methyl-N-Nitrosourea Induced Mammary Carcinogenesis with Raloxifene and Melatonin: Metabolic Changes in Female Rats

M¹,

Kubatka²,

Kalicka³

et al. 2002

Acta Vet. Brno

View full text Add to dashboard Cite

Chamilová M., P. Kubatka, K. Kalická, E. Adámeková, B. Bojková, I. Ahlers, E. Ahlersová: Chemoprevention of N-methyl-N-nitrosourea Induced Mammary Carcinogenesis with Raloxifene and Melatonin: Metabolic Changes in Female Rats. Acta Vet. Brno 2002, 71: 235-242.The aim of this work was to determine the selected parameters of carbohydrate and lipid metabolism in the mammary carcinogenesis induced with N-methyl-N-nitrosourea (NMU) in two doses, each by 50 mg/kg of body weight with a 7-day interval between them within the postnatal days 43 and 54 in female Sprague-Dawley rats. Chemoprevention started with the administration of melatonin (MEL, 4 µg/ml in water, from 15.00 h to 08.00 h) 12 days and raloxifene (RAL 5 mg/kg, 2 × weekly) 10 days before the application of NMU. Twenty-four weeks following the NMU administration the animals were killed, and the incidence, latency, frequency and volume of tumours were evaluated. The animals were divided into: tumour-bearing (TB) and non-tumourbearing (NTB) with the influence of RAL, MEL and their combination. While RAL and RAL plus MEL significantly decreased the incidence and frequency of tumours, the effect of isolated MEL was substantially lower. In the serum, an increase in the concentration of serum glucose in TB and also NTB animals was observed. In the liver of both the TB and NTB animals, the content of cholesterol (CH) and triacylglycerols (TG) decreased and the contents of phospholipids (PL) increased. RAL decreased the contents of CH and PL in the liver of NTB animals and increased the concentration of TG in both groups of animals. Administration of RAL to NTB animals decreased the concentrations of malondialdehyde (MDA) in the serum and thymus, in the bone marrow also in TB animals. MEL decreased the concentration of MDA in the bone marrow of TB animals. MEL increased the concentrations of serum glucose and glycogen content in the heart muscle of NTB animals. RAL plus MEL decreased the concentration of serum TG and PL and decreased the contents of CH and PL in the liver of TB as well as NTB animals. In the thymus and liver, combination of RAL+MEL decreased the MDA content compared with the RAL alone in NTB animals.The co-effect of two or more substances will be probably the optimal way in prevention of cancer. The co-effect of RAL and MEL shows to be a prospective way for influencing the mammary tumors. Breast cancer, female rats, raloxifene, melatonin, chemopreventionThe hormonal therapy of the breast carcinoma is an inseparable part of the variety of therapeutic procedures. The substitution with estrogens has been considered for a long time as a dominant indication of therapy in postmenopausal women, and it has been recognized that approximately one third of women will have a benefit of this procedure. The use of estrogens protects these women against osteoporosis and decreases the cardiovascular risk, but on the other hand, increases the risk of breast and endometrium carcinoma (Col et al. 1997). With regard to the unfavourable effects of estrogens on ...

show abstract

“…This reduction seems to be related to the lack of melatonin because melatonin supplements normalised glucagon levels within 1 h of the injection, and subsequently increased circulating glucagon levels. These results differ from those obtained by Shima et al (1997), showing that acute systemic injection of melatonin does not affect plasma glucagon concentrations measured after the injection of 2-deoxy-D-glucose into the suprachiasmatic nucleus of the hypothalamus. This discrepancy may be explained by differences in experimental procedure, particularly the method used to stimulate glucagon secretion.…”

Section: Discussioncontrasting

confidence: 99%

Effects of Pinealectomy on Glucagon Responsiveness to Hypoglycaemia Induced by Insulin Injections in Fed Rats

Kosa

Maurel

Siaud

2001

Experimental Physiology

View full text Add to dashboard Cite

The glucagon response to insulin‐induced hypoglycaemia was tested in rats that had been pinealectomised (Px), pinealectomised and fitted with melatonin implants (Px + MLT), or sham‐operated (SO). The glucagon response to hypoglycaemia observed in SO rats (216 ± 27 pg ml−1 at baseline versus 397 ± 35 pg ml−1 at the hypoglycaemic peak, mean ± S.D.) was stronger than that in Px rats (180 ± 37 pg ml−1 and 229 ± 21 pg ml−1, respectively) and weaker than that in Px + MLT rats (256 ± 19 pg ml−1 and 516 ± 11 pg ml−1, respectively). Our data indicate that the capacity to release glucagon during insulin‐induced hypoglycaemia is altered in pinealectomised rats.

show abstract

Melatonin suppresses hyperglycemia caused by intracerebroventricular injection of 2-deoxy-d-glucose in rats

Cited by 30 publications

References 5 publications

Melatonin acts through MT1/MT2 receptors to activate hypothalamic Akt and suppress hepatic gluconeogenesis in rats

Melatonin acts through MT1/MT2 receptors to activate hypothalamic Akt and suppress hepatic gluconeogenesis in rats

Chemoprevention of N-Methyl-N-Nitrosourea Induced Mammary Carcinogenesis with Raloxifene and Melatonin: Metabolic Changes in Female Rats

Effects of Pinealectomy on Glucagon Responsiveness to Hypoglycaemia Induced by Insulin Injections in Fed Rats

Contact Info

Product

Resources

About