Protective effect of melatonin on β-cell damage in streptozotocin-induced diabetes in rats

Yavuz, Özlem; Cam, Meryem; Bukan, Neslihan; Güven, Aysel; Sılan, Fatma

doi:10.1078/0065-1281-00711

Cited by 61 publications

(37 citation statements)

References 37 publications

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“…Furthermore, diabetic rats showed stable diurnal rhythms of the variables listed above. These findings suggest that the pineal gland with its enhanced synthesis of the synchronising hormone melatonin and intact circadian oscillations of Aanat, Hiomt and the clock genes can compensate for severe metabolic disturbances [34]. These results are in contrast to data of others, for example Champney et al , h), and of insulin receptor (Insr) in male (i, j) and female (k, l) rat pineal glands.…”

Section: Discussioncontrasting

confidence: 56%

The insulin–melatonin antagonism: studies in the LEW.1AR1-iddm rat (an animal model of human type 1 diabetes mellitus)

et al. 2011

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Aims/hypothesis It is well documented that melatonin influences insulin secretion mediated by G-protein-coupled melatonin receptor isoforms MT1 and MT2, which are present in rat and human pancreatic islets, as well as in rat insulinoma cells. Recent investigations have proven that hyperinsulinaemic Goto-Kakizaki (GK) rats, which are a rat model of type 2 diabetic rats, and humans have decreased melatonin plasma levels, whereas a streptozotocin-induced rat model of diabetes developed reduced insulin levels combined with increased melatonin levels. Methods Plasma levels of glucose, insulin and melatonin as well as RNA expression of pineal Aanat, Hiomt (also known as Asmt), insulin receptor, adrenoceptor β1 and the clock genes Per1 and Bmal1 (also known as Arntl) were determined in male and female LEW.1AR1-iddm rats as well as in insulin-substituted LEW.1AR1-iddm rats.Results Severe hypoinsulinaemia in diabetic LEW.1AR1-iddm rats was associated with decreased body weight and increased melatonin plasma levels combined with mainly elevated expression of Aanat, Hiomt, pineal insulin receptor and adrenoceptor β1. The changes were normalised by insulin substitution. Diurnal profiles of plasma melatonin and of antagonistic clock genes Per1 and Bmal1 were maintained in diabetic and insulin-substituted rats. Conclusions/interpretation The assumed causal relation between elevated melatonin and reduced insulin levels in LEW.1AR1-iddm rats is supported by the observation that insulin substitution normalised these changes. Further support for this interpretation comes from the observation that in GK rats an increase of plasma insulin was combined with a decrease of plasma noradrenaline (norepinephrine), the most important activator of melatonin synthesis. These relationships between the noradrenergic and insulin pathway support the existence of melatonin-insulin antagonism.

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Section: Discussioncontrasting

confidence: 56%

The insulin–melatonin antagonism: studies in the LEW.1AR1-iddm rat (an animal model of human type 1 diabetes mellitus)

et al. 2011

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“…Melatoninin Beta hücrelerini koruması ve insülin sekresyonu uyarımını arttırması gibi terapatik etkilerini de oksidatif stresi azaltarak ve beta hücre bütünlüğünü koruyarak gösterdiği belirtilmiştir [7]. Yapılan çalışmada insülin tedavisinin STZ ile oluştu-rulan tip 1 diyabette biyomekanik kemik bozulması restorasyonunda başarısız olduğu belirtilmiştir [40].…”

Section: Açlık Kan şEkeri Düzeyleriunclassified

“…Yapılan çalışmalarda melatonin pankreas beta hücrelerinin de oksidatif stresi azaltarak ve hücre bütünlüğünü koruyarak etki göstermiştir [7].…”

Section: Introductionunclassified

The possible protective effect of melatonin on streptozotocin induced experimental diabetes

Yüzüak

Aybak²

2014

J Clin Exp Invest

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Objective: This experimental study aims to investigate the protective effect of melatonin on the enzymes', which regulate glucose metabolism in liver tissue. Methods:In this experimental study, four-month-old male Wistar albino rats were used. The rats were divided into 4 groups as 7 rats in each group. Rats were grouped as control group, diabetic group, melatonin protecting group, as well as melatonin treatment group. Before the streptozotocin implementation to melatonin protecting group (seven days ago) everyday at 18.00 melatonin was implemented for seven days. On the other hand melatonin was implemented to melatonin treatment group after streptozotocin implementation everyday at 18.00 for seven days. Only a single dose of streptozotocin was implemented to diabetic group. Control group had no intervention throughout the study. In the end of the experiment, blood was taken and rats were sacrificed. Before the sacrifice process rats' fasting blood pressure was measured. Hexokinases, pyruvate kinase, glucose-6-phosphatase, fructose -1,6-bisphosphatase, glucose -6 phosphate dehydrogenase levels were measured in the liver samples.Results: Between control and experimental groups of rats, there are statistically significant differences between control and experimental groups for all parameters. Melatonin protecting group levels of investigated parameters were more close to that of control groups' values and results are statistically significant. Moreover, melatonin treatment group showed a protective effect. However it is not effective as melatonin protecting group. Conclusion:It can be suggested that melatonin shows protective effect on enzymes related to glucose metabolism in the liver tissue in a model of streptozotocin-induced experimental diabetes. J Clin Exp Invest 2014; 5 (4): 592-598Key words: Melatonin, liver, diabetes, streptozotocin. ÖZETAmaç: Bu deneysel çalışmada streptozotosin ile oluştu-rulmuş deneysel diyabette, melatoninin karaciğer dokusunda glikoz metabolizmasını düzenleyen enzimler üze-rindeki koruyucu etkisini araştırmayı amaçladık.Yöntemler: Bu deneysel çalışmada dört aylık erkek Wistar albino sıçanlar kullanıldı. Çalışmamız için her grupta yedi hayvan olmak üzere dört grup oluşturuldu. Sıçanlar; kontrol grubu, diyabet grubu, melatonin koruyucu grup, melatonin tedavi grubu şeklinde gruplandırıldı. Melatonin koruyucu gruba streptozotosin uygulanmasından yedi gün öncesinden başlanılarak her gün saat 18.00'da, melatonin tedavi grubuna ise streptozotosin uygulandıktan sonra yedi gün süresince her gün saat 18.00'da melatonin uygulandı. Diyabet grubuna sadece streptozotosin tek doz uygulandı. Kontrol grubuna herhangi bir işlem yapıl-madı. Çalışma sonunda sıçanların kalbinden kan alınarak sakrifiye edildi. Sakrifiye işlemi öncesinde açlık kan şe-kerleri ölçüldü. Alınan karaciğer örneklerinde Hekzokinaz, Pirüvat Kinaz, Glikoz -6-Fosfataz, Fruktoz -1,6-Bifosfataz, Glikoz -6-Fosfat Dehidrogenaz düzeyleri ölçüldü. Bulgular: Sıçanların kontrol ve deney grupları arasında tüm parametreler açısından i...

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“…Melatonin is a free radical and peroxynitrite scavenger [652][653][654], and exerts anti-inflammatory effects, including inhibition of NF-κB activation [653,655,656], prevention of iNOS expression and direct inhibition of catalytic activity of NOS [657], decrease malondialdehyde production and increase glutathione peroxidase activity [658][659][660]. Also two melatonin metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine and N1-acetyl-5-methoxykynuramine, exerted potent anti-inflammatory and antioxidant effects [661,662].…”

Section: Beneficial Role Of the Increased Indoleamine 23-dioxygenasementioning

confidence: 99%

T. gondii Infection Acquired during Pregnancy and/or after Birth may be Responsible for Development of both Type 1 and 2 Diabetes Mellitus

Pr¹,

ota²

2013

J Diabetes Metab

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Recently, it was suggested that maternal T and potentially B cells transferred during pregnancy and/or the breast milk feeding and their encounter with the antigen in mesenteric lymph nodes might play a role in development of type 1 diabetes mellitus (T1DM). T. gondii infection during gestation and/or after birth may be responsible for development of both T1DM and T2DM in children, adolescents and adults because: a) maternal microchimerism in peripheral blood was demonstrated to be significantly higher in patients with T1DM compared to unaffected siblings and healthy subjects, b) transmission of T. gondii as a Trojan horse in various types of eukaryotic cells, including T and B lymphocytes, c) swallowing by the fetus of amniotic fluid containing infected leukocytes and other cells, d) elimination of T. gondii in the breast milk during lactation, e) involvement of mesenteric lymph nodes after oral infection with the parasite, and f) damage of the myenteric neurons during infection with the parasite in both the animals with streptozotocin-induced diabetes and diabetic patients. Moreover, a significantly lower occurrence of antibodies against T. gondii found in the sera of patients with T1DM compared with their first-degree family members or healthy controls may be due to their T and/or B cell exhaustion perspective caused by chronic infection with the parasite. This suggestion may be supported by the finding that latent toxoplasmosis was associated with markedly reduced lymphocyte B-cell counts responsible for production of antibodies, markedly lower serum IgG, IgM, and IgA levels, and a significant suppression of IL-2. On the other hand, patients with T2DM had increased anti-T. gondii antibodies significantly more frequently than respective controls. Impaired vascular endothelial function characteristic for the patients with diabetes mellitus may be at least in part due to the preferential T. gondii infection of endothelial cells. Vitamin D and minocycline exerted beneficial effects on development and clinical course of diabetes mellitus probably because of their immunomodulatory and antitoxoplasmatic activities. These data strongly suggest that the parasite play an important role in development of both types of diabetes mellitus.

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Protective effect of melatonin on β-cell damage in streptozotocin-induced diabetes in rats

Cited by 61 publications

References 37 publications

The insulin–melatonin antagonism: studies in the LEW.1AR1-iddm rat (an animal model of human type 1 diabetes mellitus)

The insulin–melatonin antagonism: studies in the LEW.1AR1-iddm rat (an animal model of human type 1 diabetes mellitus)

The possible protective effect of melatonin on streptozotocin induced experimental diabetes

T. gondii Infection Acquired during Pregnancy and/or after Birth may be Responsible for Development of both Type 1 and 2 Diabetes Mellitus

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