【摘要】：研究背景妊娠期糖尿病(gestational diabetes mellitus,GDM)是在妊娠期首次發(fā)生或發(fā)現(xiàn)的糖尿病,嚴(yán)重威脅孕婦及其子代健康。至今為止GDM的病因尚不清楚,眾多研究一致認(rèn)為是多種因素共同作用的結(jié)果。胰島素抵抗(insulin resistance,IR)及由于胰島素抵抗帶來(lái)的糖脂代謝紊亂是目前公認(rèn)的GDM發(fā)病的病理生理基礎(chǔ),而胰島素信號(hào)通路的異常是IR發(fā)生的主要原因。近年來(lái),來(lái)源于脂肪組織的脂肪因子(Adipokines)與GDM的關(guān)系倍受關(guān)注,已成為新的研究熱點(diǎn)。課題組前期研究發(fā)現(xiàn),在GDM孕婦血清、體內(nèi)網(wǎng)膜組織以及胎盤(pán)組織中,Omentin-1明顯降低,而Chemerin、Vaspin則明顯升高。研究結(jié)果表明脂肪因子Omentin-1、Chemerin、Vaspin與GDM的胰島素抵抗可能存在關(guān)聯(lián)。但前期研究局限于血清和人體內(nèi)組織學(xué)的研究,只是揭示了三者與GDM之間存在的這種表象,同時(shí),帶來(lái)了新的問(wèn)題,即Omentin-1、Chemerin、Vaspin與GDM的胰島素抵抗是否存在因果關(guān)系問(wèn)題,如果存在,那么是脂肪因子的變化導(dǎo)致了 GDM胰島素抵抗的發(fā)生?還是GDM胰島素抵抗的發(fā)生導(dǎo)致了脂肪因子的變化?脂肪因子與GDM胰島素抵抗的機(jī)制,著重在于脂肪因子與胰島素受體后信號(hào)分子的表達(dá)及磷酸化水平之間的關(guān)聯(lián)。為進(jìn)一步探討脂肪因子Omentin-1、Chemerin、Vaspin與GDM胰島素抵抗是否存在必然聯(lián)系及具體機(jī)制,本研究在前期研究基礎(chǔ)上,建立GDM大網(wǎng)膜前脂肪細(xì)胞原代培養(yǎng)及增殖分化模型,以體外培養(yǎng)GDM脂肪細(xì)胞為載體,檢測(cè)脂肪因子Omentin-1、Chemerin、Vaspin在不同程度過(guò)表達(dá)狀態(tài)下,脂肪細(xì)胞中胰島素受體下游信號(hào)分子(胰島素受體底物-1/2(insulin receptor substrate,IRS-1/2)、磷脂酰肌醇-3 激酶(phosphatidyl inositol-3 kinase,PI3K))mRNA及蛋白表達(dá),IRS-1/2酪氨酸磷酸化水平的變化,并最終以脂肪細(xì)胞葡萄糖攝取率的變化為驗(yàn)證,從胰島素經(jīng)典信號(hào)傳導(dǎo)通路(IRS-1/-2、PI3K)探討脂肪因子Omentin-1、Chemerin、Vaspin與GDM胰島素抵抗的內(nèi)在聯(lián)系,為研究GDM發(fā)病機(jī)理和治療策略提供線索。實(shí)驗(yàn)分為兩部分第一部分GDM大網(wǎng)膜前脂肪細(xì)胞原代培養(yǎng)及增殖分化模型的建立[目的]建立妊娠期糖尿病(GDM)患者大網(wǎng)膜前脂肪細(xì)胞原代培養(yǎng)及向成熟脂肪細(xì)胞增殖分化的模型,為GDM患者脂肪因子體外脂肪細(xì)胞表達(dá)等后續(xù)研究奠定基礎(chǔ)。[方法]使用改良的細(xì)胞培養(yǎng)法,以GDM剖宮產(chǎn)患者大網(wǎng)膜純脂肪組織為原材料,作前脂肪細(xì)胞的原代培養(yǎng)及傳代,繪制傳代前脂肪細(xì)胞的生長(zhǎng)曲線,并對(duì)傳代前脂肪細(xì)胞做誘導(dǎo)分化,對(duì)已誘導(dǎo)分化細(xì)胞進(jìn)行油紅O染色、甘油磷酸脫氫酶(GPDH)動(dòng)態(tài)變化測(cè)定、油紅O染色提取法測(cè)定脂肪細(xì)胞內(nèi)脂肪含量及RT-PCR檢測(cè)脂聯(lián)素mRNA表達(dá),鑒定是否已誘導(dǎo)為成熟脂肪細(xì)胞,并進(jìn)行細(xì)胞凍存與復(fù)蘇實(shí)驗(yàn)。[結(jié)果]1、培養(yǎng)6 h即有部分細(xì)胞貼壁,13 h貼壁率70%,24 h后基本全部貼壁。2、培養(yǎng)出的前脂肪細(xì)胞基本均為梭形細(xì)胞,增殖旺盛,第4天細(xì)胞開(kāi)始快速增殖,從生長(zhǎng)曲線可見(jiàn)倍增時(shí)間大約為48 h左右。3、第7天原代前脂肪細(xì)胞逐漸由梭形變?yōu)闄E圓形或圓形,胞內(nèi)開(kāi)始出現(xiàn)脂肪顆粒,而傳代細(xì)胞仍然保持梭形和無(wú)脂滴。4.、第9天原代前脂肪細(xì)胞已開(kāi)始出現(xiàn)大量脂肪顆粒,而傳代細(xì)胞至第9天后仍繼續(xù)保持梭形,細(xì)胞基本單層融合,排列緊密,油紅O染色顯示仍未著色。5、傳代后前脂肪細(xì)胞前4天細(xì)胞形態(tài)及生長(zhǎng)狀況與原代前脂肪細(xì)胞極為相似,基本為梭形,大小較為均勻。第5-6天后細(xì)胞進(jìn)入快速增殖,排列平行緊密,通常第7天即可完成單層融合。6、前脂肪細(xì)胞在一定濃度胰島素(10μg/ml)和地塞米松(1umol/L)的誘導(dǎo)作用下,GPDH開(kāi)始上升并迅速增加,9天左右到達(dá)高峰并維持在高水平,形態(tài)上表現(xiàn)為3天后部分細(xì)胞開(kāi)始出現(xiàn)單個(gè)散在脂滴,隨著分化時(shí)間延長(zhǎng),脂滴逐漸增多,胞質(zhì)中出現(xiàn)圍繞細(xì)胞核的小脂滴,11天左右到達(dá)高峰,與油紅O染色定量結(jié)果相吻合。7、RT-PCR檢測(cè)脂聯(lián)素mRNA表達(dá),由電泳結(jié)果可見(jiàn)分化后的細(xì)胞有脂聯(lián)素mRNA表達(dá),前脂肪細(xì)胞無(wú)脂聯(lián)素mRNA表達(dá)。[結(jié)論]1、GDM大網(wǎng)膜脂肪組織中具有前脂肪細(xì)胞,以課題組改良法培養(yǎng)出的人源前脂肪細(xì)胞成分均一,增殖旺盛,倍增時(shí)間為48h左右。可進(jìn)行連續(xù)傳代和大量擴(kuò)增,一般在5代以內(nèi)細(xì)胞增殖迅速,再往后則增殖和分化率開(kāi)始降低。2、原代前脂肪細(xì)胞在培養(yǎng)增殖過(guò)程中,會(huì)自然出現(xiàn)向成熟脂肪細(xì)胞的分化,而傳代后前脂肪細(xì)胞則失去了分化的能力,可能與原代細(xì)胞仍然會(huì)攜帶某些體內(nèi)誘導(dǎo)因子有關(guān);3、前脂肪細(xì)胞可被誘導(dǎo)而分化,一定量的胰島素(10μg/ml)和地塞米松(lumol/L)在前脂肪細(xì)胞的分化中起重要作用,是其啟動(dòng)和促進(jìn)因子,誘導(dǎo)后分化率高,可達(dá)80%左右;4、誘導(dǎo)后細(xì)胞內(nèi)脂肪含量的增加比GPDH的出現(xiàn)要晚6天左右,酶的出現(xiàn)在先,脂肪出現(xiàn)在后;5、傳代前脂肪細(xì)胞可進(jìn)行凍存和復(fù)蘇,經(jīng)適當(dāng)誘導(dǎo)后可定向分化為成熟脂肪細(xì)胞,脂肪細(xì)胞模型的建立,為后續(xù)脂肪細(xì)胞體外實(shí)驗(yàn)研究做好了前期準(zhǔn)備。第二部分Omentin-1、Chemerin、Vaspin體外過(guò)表達(dá)對(duì)胰島素信號(hào)傳導(dǎo)通路的影響[目的]以體外培養(yǎng)GDM前脂肪細(xì)胞為載體,探討脂肪因子Omentin-1、Chemerin、Vaspin在過(guò)表達(dá)狀態(tài)下,脂肪細(xì)胞胰島素受體下游信號(hào)分子胰島素受體底物-1/2(IRS-1/2)、磷脂酰肌醇-3激酶(PI3K)mRNA及蛋白表達(dá),IRS-1/2酪氨酸磷酸化水平的變化,以及細(xì)胞葡萄糖攝取率變化,從胰島素IRS-1/2、PI3K(P85α)信號(hào)傳導(dǎo)通路探討脂肪因子Omentin-1、Chemerin、Vaspin與GDM胰島素抵抗的內(nèi)在聯(lián)系。[方法]復(fù)蘇、傳代及誘導(dǎo)分化GDM前脂肪細(xì)胞,構(gòu)建人源Omentin-1、Chemerin、Vaspin過(guò)表達(dá)質(zhì)粒,利用大腸桿菌表達(dá)系統(tǒng)進(jìn)行質(zhì)粒轉(zhuǎn)化、擴(kuò)大培養(yǎng)和提取;以3個(gè)過(guò)表達(dá)梯度(1.0μμg 2.5μg、5.0μg)轉(zhuǎn)染GDM人源第3代傳代脂肪細(xì)胞(每個(gè)濃度轉(zhuǎn)染6孔,3系共18個(gè)數(shù)據(jù)),以無(wú)轉(zhuǎn)染組為對(duì)照;Q-PCR檢測(cè)細(xì)胞中Omentin-1、Chemerin、Vaspin、胰島素受體底物-1/2(IRS-1/2)、磷脂酰肌醇-3激酶(PI3K(P85α))mRNA 表達(dá),Western Blot 檢測(cè)細(xì)胞中 Omentin-1、Chemerin、Vaspin、IRS-1、IRS-2、PI3K(P85α)蛋白表達(dá)及 IRS-1/2 酪氨酸磷酸化水平,[3H]-2-脫氧-D-葡萄糖攝取測(cè)定法檢測(cè)不同濃度轉(zhuǎn)染組細(xì)胞葡萄糖攝取率的變化。統(tǒng)計(jì)分析時(shí)各系以0.0μg組均值為標(biāo)準(zhǔn),其余3組以相應(yīng)比值的x±s進(jìn)行標(biāo)化和量化,SPSS 20.0軟件統(tǒng)計(jì)處理。[結(jié)果]1、Omentin-1、Chemerin、Vaspin mRNA及蛋白表達(dá)隨轉(zhuǎn)染濃度梯度升高而表達(dá)量增加(P均0.05),所構(gòu)建過(guò)表達(dá)載體有效;2、隨Omentin-1表達(dá)增加,轉(zhuǎn)染人源Omentin-1脂肪細(xì)胞中IRS-1、PI3K(P85α)mRNA及蛋白表達(dá)明顯增加(P均0.05),IRS-2 mRNA及蛋白表達(dá)未發(fā)生明顯變化(P均0.05),IRS-1磷酸化程度明顯升高(P=0.031),IRS-2磷酸化程度未發(fā)生明顯變化(P=0.685),葡萄糖攝取率上升(P=0.024);3、隨Chemerin表達(dá)增加,轉(zhuǎn)染人源Chemerin脂肪細(xì)胞中IRS-1/2、PI3K(P85α)mRNA及蛋白表達(dá)未出現(xiàn)明顯變化(P均0.05),但存在IRS-1磷酸化程度明顯增加(P=0.041),IRS-2磷酸化程度變化不明顯(P=0.585),脂肪細(xì)胞葡萄糖攝取率略有增加,但無(wú)統(tǒng)計(jì)學(xué)差別(P=0.064);4、隨Vaspin表達(dá)增加,轉(zhuǎn)染人源Vaspin脂肪細(xì)胞中IRS-1、IRS-2、PI3K(P85α)mRNA及蛋白表達(dá)均未發(fā)生明顯變化(P均0.05),IRS-1、IRS-2酪氨酸磷酸化程度均未出現(xiàn)明顯變化(P均0.05),葡萄糖攝取率變化不明顯(P=0.656)。[結(jié)論]1、Omentin-1與GDM胰島素抵抗存在緊密的聯(lián)系,Omentin-1是機(jī)體的保護(hù)因子,對(duì)肥胖、糖尿病等具有拮抗作用,Omentin-1的表達(dá)下降是機(jī)體發(fā)生胰島素抵抗的重要原因之一,GDM胰島素抵抗發(fā)生,是Omentin-1表達(dá)下降的果。其增敏機(jī)制是Omentin-1的表達(dá)可能通過(guò)某種途徑激活了 IRS-1/PI3K(P85 α)信號(hào)通路,導(dǎo)致了 IRS-1表達(dá)增加和磷酸化活化,促進(jìn)了 PI3K的活化和表達(dá),從而提高脂肪細(xì)胞葡萄糖的攝取,發(fā)揮其胰島素增敏作用,而與IRS-2沒(méi)有明顯關(guān)聯(lián)。2、Chemerin在GDM血清及網(wǎng)膜脂肪組織中的高表達(dá),可能與GDM的胰島素抵抗存在一定的關(guān)聯(lián),但更多的可能,是對(duì)GDM肥胖、慢性炎癥狀態(tài)及胰島素抵抗的一種補(bǔ)償機(jī)制,更傾向于是GDM胰島素抵抗的結(jié)果。其一定程度促進(jìn)IRS-1酪氨酸磷酸化的機(jī)制,以及是否通過(guò)了其他途徑一定程度上增加了機(jī)體對(duì)胰島素敏感,尚不明確,還有待于進(jìn)一步研究。3、Vaspin 與 IRS-1、IRS-2、PI3K(P85α)并不存在明顯關(guān)聯(lián),Vaspin 的升高不會(huì)導(dǎo)致GDM的胰島素抵抗,Vaspin在GDM血清及網(wǎng)膜脂肪組織中的高表達(dá),不是胰島素抵抗的因,而是GDM機(jī)體存在的脂肪蓄積、高血糖及高脂血癥狀態(tài)與Vaspin的一種交互影響的結(jié)果。臨床上可以此作為一種衡量孕婦脂代謝紊亂程度和是否存在慢性炎癥狀態(tài)的“代謝紊亂標(biāo)志”,但與GDM胰島素抵抗的發(fā)生沒(méi)有直接的必然的聯(lián)系。
[Abstract]:Background gestational diabetes mellitus (GDM) is the first occurrence or discovery of diabetes in pregnancy, which is a serious threat to the health of pregnant women and their offspring. So far, the cause of GDM is not clear. Many studies have agreed to be a result of the combination of various factors. Insulin resistance (insulin resistance, IR) and the cause of the pancreas. The disorder of glycolipid metabolism caused by Isle resistance is the pathophysiological basis of GDM, and the abnormal insulin signaling pathway is the main cause of IR. In recent years, the relationship between adipose tissue derived from adipose tissue (Adipokines) and GDM has attracted much attention and has become a new research hotspot. In the women's serum, in the omentum tissue and in the placenta, the Omentin-1 was significantly reduced, while the Chemerin and Vaspin were significantly increased. The results showed that the insulin resistance of Omentin-1, Chemerin, Vaspin and GDM may be associated. However, the previous study was limited to the study of serum and human histology, but only revealed the relationship between the three and GDM. The existence of this representation brings new questions: whether there is a causal relationship between the insulin resistance of Omentin-1, Chemerin, Vaspin and GDM, if there is a change in the fat factor that leads to the occurrence of GDM insulin resistance, or is the occurrence of GDM insulin resistance leading to a change in the fat factor, the fat factor and the GDM The mechanism of insulin resistance lies in the association between the expression of adipose factors and the expression of post insulin receptor signaling molecules and the level of phosphorylation. In order to further investigate whether there is an inevitable relationship and specific mechanism of adipose factor Omentin-1, Chemerin, Vaspin and GDM insulin resistance, this research is based on the preliminary Study on the establishment of GDM great omentum fat. The primary culture and proliferation and differentiation model of the adipose cells were used to culture GDM adipocytes in vitro, and to detect the adipose factor Omentin-1, Chemerin, and Vaspin at different levels of overexpression. The downstream signal molecules of insulin receptor (-1/2 (insulin receptor substrate, IRS-1/2) and phosphatidyl inositol -3 kinase (PHO) in adipocytes Sphatidyl inositol-3 kinase, PI3K) mRNA and protein expression, the changes in the level of IRS-1/2 tyrosine phosphorylation, and finally verified by the changes in the glucose uptake rate of adipocytes. The internal relationship between the fat factor Omentin-1, Chemerin, Vaspin and GDM insulin resistance is discussed from the insulin classical signal transduction pathway (IRS-1/-2, PI3K). The pathogenesis and treatment strategy provide clues. The experiment is divided into two parts: the first part of the two part of the primary adipocyte preadipocyte culture and proliferation and differentiation model establishment [Objective] to establish the primary culture of preadipocyte preadipocytes and the proliferation and differentiation of mature adipocytes in patients with gestational diabetes mellitus (GDM), for the in vitro adipose factor of GDM patients. A modified cell culture method was used to use the modified cell culture method. The primary adipose tissue of the GDM caesarean section was used as the raw material, the primary culture and generation of preadipocytes, the growth curve of preprepassable adipocytes were plotted, and the pre passages were induced and differentiated, and the differentiated cells were induced into the differentiated cells. Oil red O staining, glycerol phosphate dehydrogenase (GPDH) dynamic change determination, oil red O staining method to determine fat content in adipocytes and RT-PCR detection of adiponectin mRNA expression, identification has been induced into mature adipocytes, and cell cryopreservation and resuscitation experiment. [results]1, 6 h, a part of cell adherence, 13 H adherence rate 70%, 24 h After almost all the adherent.2, the cultured preadipocytes were basically spindle cells, proliferating and proliferating, and the cells began to proliferate quickly on the fourth day. The multiplication time was about 48 h.3 from the growth curve, and the primary adipocytes were gradually oval or round, and the fat particles began to appear in the cell, and the passages were still preserved in the seventh days. With shuttle and fat free.4., a large number of fat particles have begun to appear in the ninth day pregeneration adipocytes, while the cells of the passages continue to remain spindle shaped after ninth days. The cells are basically monolayer and closely arranged. The oil red O staining shows that the.5 is still not stained, and the fine cell morphology and growth status of the preadipocyte before the generation and the pre generation adipocytes are very different from those of the original preadipocytes. Similar, basically spindle shape, the size is more uniform. After 5-6 days, the cells enter the rapid proliferation, the arrangement is parallel and close, usually seventh days can complete the single layer fusion.6, the preadipocytes in a certain concentration of insulin (10 mu g/ml) and dexamethasone (1umol/L) induced, GPDH began to rise and rapidly increase, 9 days to reach the peak and maintain high Level, after 3 days, the cells began to appear single scattered in the lipid droplets. As the time of differentiation extended, the lipid droplets increased gradually, and the small fat droplets around the nucleus appeared in the cytoplasm, reaching the peak at about 11 days, and anastomosing.7 with the quantitative results of the oil red O staining. The expression of lipoplex mRNA was detected by RT-PCR, and the differentiated cells were visible from the electrophoresis results. The expression of adiponectin mRNA, the preadipocytes without adiponectin mRNA expression. [conclusion]1, GDM omentum adipose tissue has preadipocytes in the adipose tissue, and the preadipocytes of human preadipocytes are homogenized, proliferate, and the multiplication time is about 48h. After that, the proliferation and differentiation rate began to decrease.2, and the preadipocytes would naturally appear to mature adipocytes during the process of culture and proliferation, while preadipocytes lost their ability to differentiate, which may be related to the primary cells, and 3, preadipocytes can be induced and differentiated. A certain amount of insulin (10 g/ml) and dexamethasone (lumol/L) play an important role in the differentiation of preadipocytes. It is the promoter and promoting factor, and the induced differentiation rate is high, up to about 80%. 4, the increase of intracellular fat content after induction is 6 days left right later than that of GPDH, the enzyme appears first, fat appears in the post, and 5, fat fine before passage. The cell can be frozen and resuscitation, and can be differentiated into mature adipocytes after proper induction. The establishment of adipocyte model is ready for the subsequent study of adipocytes in vitro. Second the effect of overexpression of Omentin-1, Chemerin and Vaspin on insulin signaling pathway in vitro [Objective] to cultivate preadipose fat before GDM in vitro Cells were used to explore the expression of insulin receptor substrate -1/2 (IRS-1/2), phosphatidylinositol -3 kinase (PI3K) mRNA and protein expression, the changes in the level of IRS-1/2 tyrosine phosphorylation, and the changes in the glucose uptake rate of cells from the islets of the adipocyte Omentin-1, Chemerin and Vaspin. The intrinsic relationship between adipose factor Omentin-1, Chemerin, Vaspin and GDM insulin resistance was investigated by IRS-1/2, PI3K (P85 alpha) signal transduction pathway. [Methods] resuscitation, generation and induction of differentiation of pre GDM preadipocytes, constructing human Omentin-1, Chemerin, Vaspin overexpressed plasmids, using Escherichia coli expression system for plasmid transformation, and expanding culture and extraction; GDM human third generation adipocytes were transfected with 3 overexpression gradients (1 mu g, 2.5 mu g, 5 g), which were transfected with 6 pores and 3 lines with 18 data, and Q-PCR was used to detect Omentin-1, Chemerin, Vaspin, the insulin receptor substrate -1/2 (IRS-1/2), and phosphatidylinositol -3 kinase (PI3K (PI3K)). The expression of Omentin-1, Chemerin, Vaspin, IRS-1, IRS-2, PI3K (P85 alpha) protein and the level of IRS-1/2 tyrosine phosphorylation were detected. The changes of glucose uptake in the cells of different concentrations were detected by the [3H]-2- deoxy -D- glucose uptake assay. The statistical analysis was based on the mean of the 0 mu g group, and the other 3 groups were fed with the corresponding ratio X. SPSS 20 software statistical processing. [results]1, Omentin-1, Chemerin, Vaspin mRNA and protein expression increased with the increase of transfection concentration gradient (P 0.05), and the expression vector was constructed effectively; 2, with the increase of Omentin-1 expression, the expression of IRS-1, PI3K (P85 alpha) and protein expression increased obviously. Addition (P 0.05), IRS-2 mRNA and protein expression did not change significantly (P 0.05), IRS-1 phosphorylation level increased significantly (P=0.031), IRS-2 phosphorylation level did not change significantly (P=0.685), glucose uptake rate increased (P=0.024); 3, as Chemerin expression increased, transfected into human Chemerin fat cells, IRS-1/2, protein expression and protein expression There was no obvious change (P 0.05), but there was a significant increase in the degree of phosphorylation of IRS-1 (P=0.041), the degree of IRS-2 phosphorylation was not significantly changed (P=0.585), and the glucose uptake rate of adipocytes was slightly increased, but there was no statistical difference (P=0.064); 4, with the increase of Vaspin expression, the transfection of IRS-1, IRS-2, PI3K (P85 alpha) and protein tables in human Vaspin adipocytes There was no obvious change (P 0.05), IRS-1, IRS-2 tyrosine phosphorylation level did not change significantly (P 0.05), glucose uptake rate changes (P=0.656). [conclusion]1, Omentin-1 and GDM insulin resistance is closely linked, Omentin-1 is the body's protective factor, obesity, diabetes and other antagonistic effects, Omentin-1. The decrease of expression is one of the important causes of insulin resistance in the body. GDM insulin resistance is the result of the decline of Omentin-1 expression. Its sensitization mechanism is that the expression of Omentin-1 may activate the IRS-1/PI3K (P85 alpha) signaling pathway through some way, which leads to the activation of IRS-1 expression and phosphorylation, and promotes the activation and table of PI3K. As a result, it improves the uptake of glucose in adipocyte and plays its insulin sensitizing effect, but has no obvious association with IRS-2, and the high expression of Chemerin in GDM serum and omentum adipose tissue may be associated with the insulin resistance of GDM, but more likely, it is a kind of GDM obesity, chronic inflammatory state and insulin resistance. The compensation mechanism is more likely to be the result of GDM insulin resistance. To a certain extent, the mechanism of the tyrosine phosphorylation of IRS-1, and whether the body is sensitid to insulin to some extent through other ways, is not clear, and further study of.3, Vaspin and IRS-1, IRS-2, and PI3K (P85 alpha) have no obvious association, Vaspi The increase of N does not lead to insulin resistance in GDM. The high expression of Vaspin in GDM serum and omentum adipose tissue is not the cause of insulin resistance, but is the result of the accumulation of fat in GDM body, the interaction of hyperglycemia and hyperlipidemia with Vaspin. This can be used as a measure of the degree of lipid metabolism disorder in pregnant women. And whether there is a "metabolic disorder marker" in chronic inflammatory state, but it is not directly related to the occurrence of GDM insulin resistance.
【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R714.256

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本文編號(hào)：2141003