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The Relationship Of Adipocytokines With Obesity And Diabetes, And Studies On Expression And Intervention Of Adiponectin And Adiponectin-receptor In Human Adipocytes

Posted on:2008-03-30Degree:MasterType:Thesis
Country:ChinaCandidate:J Y ZhouFull Text:PDF
GTID:2144360215463510Subject:Endocrinology
Abstract/Summary:PDF Full Text Request
With the economic development of modern society and dramaticchanges of life style, the prevalence of obesity and diabetes is increasingrapidly. Both are considered as a public health problem requiringconcerted action. They are polygenic multifactorial complex diseasescaused by interaction of both heredity and environment. Existingresearches showed that insulin resistance was the central link of multiplemetabolic disorders related to obesity. It was also the common rootrelated to the development of obesity and type 2 diabetes. So it is a keypoint of the treatment of obesity and type 2 diabetes to improve insulinresistance.As a new endocrine tissue, adipose tissue may secrete manyadipocytokines, which play an important role in the maintenance of theenergy metabolic balance of the organism. Especially the latelydiscovered adiponectin, plays a critical role in improvement of insulinresistance. It has been proven by present researches that adiponectin isunique adipocytokine to have protection on human body. Adiponectin and its receptors are closely related to insulin sensitivity, so studyingadiponectin and its receptors more in depth will provide new treatmentarget for the control of metabolic disorders of obese patients. Visfatinis a kind of recently discovered new adipocytokines, mainly secretedby visceral adipose. It not only has insulin-like activity, but also couldpromote differentiation, synthesis and aggregation of adipocytes, andprobably it is the missing link to correlate obesity and diabetes.Our experimental group studied the serum levels of adipocytokines,such as visfatin and adiponectin of obese subjects, diabetic subjects, andnormal subjects on overall level, to explore the variations of theadipocytokines in the obese and diabetic subjects. We also analyzedthe association between the variations and the extent of obesity, fatdistribution pattern, insulin resistance, and others. The results showedthat①The visfatin and leptin levels in obesity and diabetic groups weresignificantly higher than those in normal group, and the adiponectin levelwas lower in the obese and diabetic than that in the normal (P<0.05).②The serum visfatin, leptin and adiponectin levels did not differ betweenthe diabetic group and obese group (P=0.450).③Visfatin level waspositively correlated with BMI, waist circumference, waist to hip ratio andleptin level, but was negatively associated with adiponectin level.④Waist circumference might more closely predict visfatin level. Itindicated that visfatin and leptin levels were significantly elevated whileadiponectin level was decreased in the obese and diabetic groups, and their levels were closely correlated with the extent and pattern of obesity.Pioglitazone, a kind of thiazolidinediones drugs (TZDs), is used as aninsulin sensitizer to treat diabetes in clinic. However it mayl cause morecumulation of adipose, whereas there is close relationship between obesityand insulin resistance, which may be contradictory on therapy. We haveset up the primary culture method and induced differentiation proposal ofhuman preadipocytes in vitro, and performed drugs intervention based onthis, studied effects of pioglitazone on proliferation and differentiationof human preadipocytes at cellular level. Besides, we explored the effectsand mechanism of pioglitazone on the expression of adiponectin and itsreceptors in human adipocytes on molecular level, so as to providetheoretical evidence for its clinical application. The results showed thatpioglitazone might significantly promote the proliferation anddifferentiation of human omental preadipocytes, and might increase theexpression of adiponectin and its receptor in human adipocytes, whichsubsequently might improve central obesity so as to enhance insulinsensitivity.
Keywords/Search Tags:Obesity, Diabetes, Adiponectin, Adiponectin-receptor, Visfatin, Pioglitazone, Human preadipocytes, Insulin sensitivity
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