肝脏胰岛素抵抗在自发性糖尿病OLETF大鼠发病中的作用

Abstract
Figure/Table
References (28)
Related Citation (12)

Download: PDF (838 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective To study the effects of hepatic insulin resistance, including the lipid deposition in livers, on preventing diabetes in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, and explore the probability of new mechanism in preventing diabetes in laboratory animals. Methods Twenty male spontaneous diabetic OLETF rats were treated as OLETF (group OLETF). Ten male Long-Evans Tokushima Otsuka (LETO) rats were used as normal control group(group LETO). Blood glucose is determined by oral glucose tolerance test. Rats were sacrificed at 8, 32 and 40 weeks and liver tissue isolated. Serum triglyceride, serum cholesterol, and serum free fatty acid (FFA) were determined. The morphological changes of livers were measured by HE stain. Based on HE results, frozen liver sections of OLETF rats of 32-week-old and 40-week-old respectively were stained with fatty Sudan Ⅲ as well as PAS before and after amylase digestion, the purpose of which is to further clarify the nature of the lesions. Results OLETF rats developed diabetes since 23 weeks of age and the incidence rate of diabetes became higher with the time goes by until got to 92.9% at 40 weeks of age when the research came to the end. No rats have developed diabetes or IGT in group LETO. The serum triglyceride, serum cholesterol, serum FFA was significantly lower in group LETO than that of group OLETF since 32 weeks (P < 0.05). With the week age increasing, liver vacuolation in group OLETF became serious and it was suggested that there appeared a gradual increase on liver fat infiltration and glycogen accumulation with a further improvement on the specific staining of fat and glycogen; while there was no significant damage in the liver structure of group LETO. Conclusion Hepatic insulin resistance may play an important part in the onset of T2DM, and the improvement of hepatic insulin resistance may work as a probable mechanism of preventing diabetes.

Key words： Type 2 diabetes OLETF rats Hepatic insulin resistance Fat deposition Lipid metabolism disorder

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	LI Jia1 XUE Yaoming2 PAN Yonghua2 ZHU Bo2 ZHANG Yan2

Cite this article:

LI Jia1 XUE Yaoming2 PAN Yonghua2 ZHU Bo2 ZHANG Yan2. The role of Hepatic insulin resistance in the pathogenesis of spontaneously diabetic OLETF rats[J]. 中国医药导报, 2018, 15(14): 12-16.

URL:

http://www.yiyaodaobao.com.cn/EN/ OR http://www.yiyaodaobao.com.cn/EN/Y2018/V15/I14/12

[1] Boden G. Obesity，insulin resistance and free fatty acids [J]. Curr Opin Endocrino Diabetes Obes，2011，18（2）：139-143.
[2] McGarry JD. Banting Lecture 2001：Dysregulation of fattyacidmetabolism in the etiology of type 2 diabetes [J]. Diabetes，2002，51（1）：7-18.
[3] Fruci B，Giuliano S，Mazza A，et al. Nonalcoholic fatty liver：a possible new target for type 2 diabetes prevention and treatment [J]. Int J Mol Sci，2013，14（11），22 933-22 966.
[4] Sato T. Insulin resistance in skeletal muscle of the male Otsuka Long-Evans Tokushima Fatty，a new model of NIDDM [J]. Diabetologia，1995，38（9）：1033-1036.
[5] Kawano K，Hirashima T，Mori S，et al. OLETF （Otsuka Long-Evans Tokushima Fatty） rat：a new NIDDM rat strain [J]. Diabetes Res Clin Pract，1994：24（supp l）：S317-S322.
[6] Mori S，Kawano K，Hirashima T，et al. Relationships between diet control and the development of spontaneous type 2 diabetes and diabetic nephropathy in OLETF rats [J]. Diabetic Res Clin Prac，1996，33（3）：145-152.
[7] D′Adamo E，Cali AM，Weiss R，et al. Central role of fatty liver in the pathogenesis of insulin in obese adolescents [J]. Diabetes Care，2010，33（8）：1817-1822.
[8] Kantarzis K，Machann J，Schick F，et al. The impact of liver fat vs visceral fat in determining categories of prediabetes [J]. Diabetologia，2010，53（5）：882-889.
[9] Neuschwander Tetri BA. Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatosis：the central role of nontriglyceride fatty acid metabolities [J]. Hepatology，2010， 52（2）：774-778.
[10] Martins AR，Nachabar RT，Gorjao R，et al. Mechanisms underlying skeletal muscle insulin resistance induced by fatty acids，importance of the mitochondrial function [J]. Lipids Health Dis，2012，11（1）：1-11.
[11] Perseghin G，Ghosh S，Gerow K. Metabolic defects in lean nondiabetic offspring of NIDDM parents：a cross-sectional study [J]. Diabetes，1997，46（6）：1001-1009.
[12] Shimabukuro M，Zhou YT，Levi M，et al. Fatty acid-induced beta cell apoptosis：a link between obesity and diabetes[J].Proc Natl Acad Sci U S A，1998，95（5）：2498-2502.
[13] Choudhury J，Sanyal AJ. Insulin resistance and the pathogenesis of nonalcoholic fatty liver disease [J]. Clin Liver Dis，2004，8（3）：575-594.
[14] DiBisceglia AM. What every hepatologist should know about endocrinology：obesity，diabetes，and liver disease [J]. Gastroenterology，2004，126（2）：604-606.
[15] Nagle CA，Klett EL，Coleman RA. Hepatic triacylglycerol accumulation and insulin resistance [J]. J Lipid Res，2009， 50（Suppl）：S74-S79.
[16] Musso G，Gambino R，Cassader M，et al. Meta-analysis：natural history of non-alcoholic fatty liver disease （NAFLD） and diagnositic accuracy of non-invasive tests for liver disease severity [J]. Ann Med，2011，43（8）：617-649.
[17] Lee Y，Yu X，Gonzales F，et al. PPAR alpha is necessary for the lipopenic action of hyperleptinemia on white adipose and liver tissue [J]. Proc Natl Acad Sci USA，2002，99（18）：11 848-11 853.
[18] Sung CK，She H，Xiong S，et al. Tumor necrosis factor-alpha inhibits peroxisome proliferators-actived receptor gamma activity at a posttranslational level in hepatic stellate cells [J]. Am J Physiol Gastrointest Liver Physiol，2004，286（5）：722-729.
[19] Neuschwander-Tetri BA，Brunt EM，Wehmeier KR，et al. Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone [J]. Hepatology，2003，38（4）：1008-1017.
[20] Patel PS，Buras ED，Balasubramanyam A. The role of the immune system in obesity and insulin resistance [J]. J Obes，2013，2013：616193.
[21] Ezhumalai M，Ashokkumar N，Pugalendi KV. Combination of carvacrol and Rosiglitazone ameliorates high fat diet induced changes in lipids and inflammatory makers in C57BL/6J mice [J]. Biochimie，2015，3（110）：129-136.
[22] Tjeerdema N，Georgiadi A，Jonker JT，et al. Inflammation increases plasma angioprotein-like protein 4 in patient with the metabolic syndrome and type 2 diabetes [J]. BMJ Open Diabetes Res Care，2014，2（1）：e00034.
[23] Eslamparast T，Eghteasd S，Poustchi H，et al. Recent advances in ditery supplementation，in treating non-alcoholic fatty liver disease [J]. World J Hepatol，2015，7（2）：204-212.
[24] Paneni F，Costantino S，Battista R，et al. Adverse epigenetic signatures by histone methytransferase set contribute to vascular dysfunction in patients with type 2 diabetes mellitus [J]. Circ Cardiovasc Genet，2015，8（1），150-158.
[25] Targher G，Byrne CD. Clinical review：nonalcoholic fatty liver disease：a novel cardiometabolic risk factor for type 2 diabetes and its complication [J]. J Clin Endocrinol Metab，2013，98（2）：483-495.
[26] Loria P，Lonardo A，Anania F. Liver and diabetes：A vicious circle [J]. Hepatol Res，2013，43（1）：51-64.
[27] Williamson RM，Price JF，Glancy S，et al. Prevalence and risk factors for hepaticsteatosis and nonalcoholic fatty liver disease in people with type 2 diabetes：the Edinburgh type 2 diabetes study [J]. Diabetes Care，2011，34（5）：1139-1144.
[28] Smith BW，Adams LA. Nonalcoholic fatty liver disease and diabetes mellitus：pathogenesis and treatment [J]. Nat Rev Endocrinol，2011，7（8）：456-465.