Study on hypoglycemic mechanism of shark hepatic stimulator substance

Abstract

Abstract: AIM: To study the hypoglycemic mechanism of shark hepatic stimulator substance (sHSS). METHODS: An experimental model of diabetes was produced by intravenous injection of alloxan.The effects of sHSS on diabetes mice were investigated by observing the changes of fasting plasma glucose, fructosamine, insulin, hepatic glycogen, erythrocytes hexokinase activity and hepatic lipoperoxide content.Primary mice hepatocytes were isolated by collagenase and injured by CCl4 or AAP.The effects of sHSS on primary mice hepatocytes were studied by observing the activity of ALT in culture supernatant. RESULTS: sHSS markedly decreased the levels of fasting plasma glucose and fructosamine, increased the content of serum insulin and hepatic glycogen and the activity of erythrocytes hexokinase in diabetes mice, and decreased the injured degree of CCl4-injured orAAP-injured primary mice hepatocytes.CONCLUSION: The hypoglycemic mechanism of sHSS may be attributed to the maintainment of pancreatic island and hepatic cells, hexokinase activity and hepatic glycogen synthesis and the antioxidative effects.

Key words: shark hepatic stimulator substance, alloxan, insulin, diabetes, hypoglycemia, hepatocyte, hexokinase, antioxidation

CLC Number:

WU Guan-Zhong, HONG Gang¹, DING Wei, LIU Guo-Qing. Study on hypoglycemic mechanism of shark hepatic stimulator substance[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(3): 318-321.

References

1 Guo Y, Kong Y, Li Q, WuWT.Purification and phy sicochemical characteristics of shark hepatic stimulator substance [J].J Chin Pharm Sci, 2001;10(2):70-4
2 郭昱, 吴梧桐, 巫冠中.鲨肝肽对小鼠肝损伤的保护作用及免疫调节作用[J].中国新药杂志, 2001;10(1):29-31
3 洪钢, 巫冠中, 刘国卿.鲨肝刺激物质对四氧嘧啶诱发的小鼠糖尿病的保护作用[J].中国药科大学学报, 2003;34(2):155-9
4 张均田.现代药理实验方法[M].北京:北京医科大学、中国协和医科大学联合出版社, 1997:981-2
5 JE Klaunig, PJ Goldblatt, DE Hinton, MM Lipsky, BF Trump. Mouse liver cell culture.I.Hepatocyte isolation[J].In Vitro, 1981;17(10):913-25
6 VM Faktor.The enzymatic isolation of hepatocytes from the mouse liver[J].Tsitologiia, 1988;30(5):644-7
7 Ohkawah, Ohisthn, Yagik.Assay for lipid peroxides in animal tissues by thiobarbituric acid action[J].Anal Biochem, 1979;95 (3):351-4
8 杜传书, 陈路明.红细胞己糖激酶测定法及中国人正常值[J].遗传与疾病, 1987;4(3):200-2
9 张均田.现代药理实验方法[M].北京:北京医科大学、中国协和医科大学联合出版社, 1997:1006-8
10 Sochor M, Baquer NZ, Hothersall JS.Effect of experimental diabetes on the activity of hexokinase isoenzymes in tissues in tissues of the rat[J].Biochem Int, 1990;22(4):467-74
11 HK Parsadanian, LP Ter-Tatevosian, HR Martikian.Changes in the activity of enzymes, participating in glycogen metabolism of alloxan diabetic rats[J].Mol Cell Biochem, 1989;90(2): 185-90
12 Reyes A, Cadenas ML.All hexokinase isoenzymes coexist in rat heaptocytes[J].Biochem J, 1984;221(3):303-9
13 Hers HG.Control of glycogen metabolism in the liver[J].Annu Rev Biochem, 1987;45(1):167-89
14 G Cotrozzi, V Casini Raggi, P Relli, G Buzzelli.Role of the liver in the regulation of glucose metabolism in diabetes and chronic liver disease[J].Ann ItalMed Int, 1997;12(1):84-91
15 W Langhans.Role of the liver in the control of glucose-lipid utilization and body weight[J].Curr Opin Clin Nutr Metab Care, 2003;6(3):449-55
16 GA Rutter.Diabetes:the importance of the liver[J].Curr Biol, 2000;10(5):R736-8
17 Baynes JW, Thorpe SR.Role of oxidative stress in diabetic complications[J].Diabetes, 1999;48(1):1-9

[1]	MA Yan, TIAN Gaopeng, SHI Xingwen, SUN Ting, XIE Jingjing, ZHEN Donghu. Correlation between 25(OH)D and metabolically related fatty liver in T2DM population [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(9): 1018-1026.
[2]	MA Xiankang, YANG Lixia, CUI Yangyang, MI Denghai. Angelica polysaccharides improve hepatic endoplasmic reticulum stress by inhibiting the expression of GRP78, p-PERK and p-Eif2α in diabetic KK-Ay mice [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(8): 926-936.
[3]	LI Kun, LI Lulu, LI Nannan, HU Weihong, ZHOU Jianchao. Effects of glycaemic control and CYP3A5 polymorphisms on tacrolimus trough concentrations after adult kidney transplantation [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(7): 767-774.
[4]	HOU Ruiying, GUO Lige, JIAO Weijie, DU Lei, WU Guiyue, ZHAO Xu. Effects of Xiaokeshu recipe on levels of serum inflammatory factors in type2 diabetic rats and its mechanism [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(4): 377-382.
[5]	ZHANG Xuejiao, LIU Jieting, LI Luxin, CHEN Peijian, DING Minglu, SUN Mengwei, CHU Yanhui, ZHANG Zhen . Effects and mechanism of dapagliflozin on myocardial injury in type 1 diabetes mice [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(3): 257-265.
[6]	ZHAO Shifeng, SONG Xiangming, YAO Jianping. Tirzepatide: A new glucagon-like peptide-1 receptor/glucose-dependent insulinotropic peptide receptor dual agonist [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(2): 220-227.
[7]	DU Xiaoyu, LI Yumeng, WU Huizhen, QIU Bo. Pharmacological and clinical evaluation of Dorzagliatin in the treatment of type 2 diabetes [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(10): 1177-1183.
[8]	CAI Jing, PAN Binjing, LIU Jingfang. Research progress on the relationship between hypoglycemic drugs and sarcopenia [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(1): 101-108.
[9]	ZHAI Weiwei, YU Qiaoling, LIU Ping, QIU Bo, WU Huizhen. Research progress of finerenone in the treatment of type 2 diabetes mellitus complicated with chronic kidney disease [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(9): 1067-1074.
[10]	WEI Feng, HE Yang, FAN Zhiqiang, LIU Shikun, OUYANG Linqi. Inhibitory effect of flufenidone on TGF-β1/Smads pathway in hepatocytes of rats with diethylnitrosamine (DEN)-induced liver injury [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(7): 739-746.
[11]	LU Senlin, LIU Xinyuan, WANG Jili, HUANG Xiaofei. Research progress of virus-mediated gene therapy in type 2 diabetes mellitu [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(7): 800-807.
[12]	ZENG Xiaofan, XU Yiqi, LIU Shu, WU Qian, LI Zibao, HE Junjun, JIN Yuelong, ZHAO Yongli, HE Chunling, GAO Jialin. Retrospectively analysis of the effect of low-dose aspirin on primary prevention of non-fatal myocardial infarction and cerebral infarction in patients with type 2 diabetes mellitus [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(6): 665-671.
[13]	LI Hao, LI Ling, XIA Zhiping, YE Qifa, PENG Guizhu. FXR agonist GW4064 ameliorates tacrolimus-induced abnormalities in glucose metabolism [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(4): 466-472.
[14]	SHAO Xi, YU Yanan, HUANG Yuhan, WANG Xiaotong, LING Hongwei, LV Dongmei, WANG Tao. Predictive factors associated with weight response to exenatide in patients with type 2 diabetes mellitus [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(3): 287-294.
[15]	QUAN Haiyan, JIANG Xing, HE Lu. Recent progress of mitophagy in hepatic insulin resistance [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(2): 198-204.