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Melatonin attenuates smoking-induced hyperglycemia via preserving insulin secretion and hepatic glycogen synthesis in rats.

ABSTRACT: Epidemiology survey indicated that cigarette smoking is a risk factor of diabetes. However, the precise mechanisms remain to be clarified. In this study, we found that smoking caused metabolic malfunctions on pancreas and liver in experimental animal model. These were indicated by hyperglycemia, increased serum hemoglobin A1c level and decreased insulin secretion, inhibition of liver glycogen synthase (LGS), and hepatic glycogen synthesis. Mechanistic studies revealed that all these alterations were caused by the inflammatory reaction and reactive oxygen species (ROS) induced by the smoking. Melatonin treatment significantly preserved the functions of both pancreas and liver by reducing ? cell apoptosis, CD68-cell infiltration, ROS production, and caspase-3 expression. The siRNA-knockdown model identified that the protective effects of melatonin were mediated by melatonin receptor-2 (MT2). This study uncovered potentially underlying mechanisms related to the association between smoking and diabetes. In addition, it is, for first time, to report that melatonin effectively protects against smoking-induced glucose metabolic alterations and the signal transduction pathway of melatonin is mainly mediated by its MT2 receptor. These observations provide solid evidence for the clinically use of melatonin to reduce smoking-related diabetes, and the therapeutic regimens are absent currently.

SUBMITTER: Li T

PROVIDER: S-EPMC5947659 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Melatonin attenuates smoking-induced hyperglycemia via preserving insulin secretion and hepatic glycogen synthesis in rats.

Li Tianjia T Ni Leng L Zhao Zhewei Z Liu Xinnong X Lai Zhichao Z Di Xiao X Xie Zhibo Z Song Xitao X Wang Xuebin X Zhang Rui R Liu Changwei C

Journal of pineal research 20180325 4

Epidemiology survey indicated that cigarette smoking is a risk factor of diabetes. However, the precise mechanisms remain to be clarified. In this study, we found that smoking caused metabolic malfunctions on pancreas and liver in experimental animal model. These were indicated by hyperglycemia, increased serum hemoglobin A1c level and decreased insulin secretion, inhibition of liver glycogen synthase (LGS), and hepatic glycogen synthesis. Mechanistic studies revealed that all these alterations ...[more]

PMID: 29437243

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Project description:Catharanthus roseus (C. roseus) and ursolic acid (UA) are ayurvedic medicines with multiple pharmacological activities including antidiabetic activity, but till date, no study is available on their combination. This study documented the antidiabetic efficacy of the combination of C. roseus and UA in rats. Rats were divided into six groups. All groups were given a single dose of Streptozotocin (STZ) at a dose of 50?mg/kg by intraperitoneal route for induction of diabetes, except the normal control group. Group 1 was treated as a normal control (NC) group and fed with saline water, Group 2 as a Diabetes Control group, Group 3 as a STZ+C. roseus ethanolic extract (CREE) group at 50?mg/kg p.o., Group 4 as a STZ+UA group orally at 50?mg/kg, Group 5 as a STZ+CREE (25?mg/kg p.o.)+UA (25?mg/kg p.o.) group, and Group 6 as a STZ+Glimepiride (0.1?mg/kg) group. Diabetes was confirmed after 72 hours by estimation of blood glucose level, and then treatment was given for the next 28 days. During the course of treatment, plasma insulin and blood glucose were measured regularly at the interval of 7 days. At the end of the protocol, blood was collected and animals were sacrificed. The glucose level, insulin level, liver glycogen storage level, and antioxidant enzymes (LPO, CAT, SOD, GPx, GST) were measured. The blood glucose level in Group 5 significantly (P < 0.001) reduced to 98.35 ± 2.45?mg/dl in comparison with that in Group 2 (321.75 ± 5.46?mg/dl). The level of plasma insulin in Group 5 increased (13.65 ± 0.10??U/ml) significantly (P < 0.01) as compared with that in Group 2 (05.93 ± 0.31??U/ml). In Group 5, the level of glycogen in liver was significantly (P < 0.01) increased as compared with that in Group 2 rats. The level of antioxidant enzymes in Group 5 restored toward normal values significantly (P < 0.01; P < 0.001) as compared with that in Group 2 animals. These findings suggest that low-dose combination of CREE and UA is effective in the treatment of diabetes.

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Melatonin attenuates smoking-induced hyperglycemia via preserving insulin secretion and hepatic glycogen synthesis in rats.

Publications

Melatonin attenuates smoking-induced hyperglycemia via preserving insulin secretion and hepatic glycogen synthesis in rats.

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