本文關(guān)鍵詞：糖尿病研究的蝙蝠動(dòng)物模型和SLC2A2基因研究　出處：《華東師范大學(xué)》2016年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 翼手目 糖尿病 動(dòng)物模型 身體質(zhì)量指數(shù) 前臂長(zhǎng)質(zhì)量指數(shù) 葡萄糖耐量實(shí)驗(yàn) SLC2A2

【摘要】：蝙蝠屬于哺乳動(dòng)物綱翼手目,物種數(shù)量占哺乳動(dòng)物的五分之一。食果蝙蝠較其它蝙蝠具有更好的維持糖穩(wěn)態(tài)、胰島素敏感性和胰島素降血糖能力,食蟲蝙蝠有在冬眠前期快速增加體重、儲(chǔ)存大量脂肪和較強(qiáng)的白色脂肪棕樣化能力,因此蝙蝠可以成為人類糖尿病研究和治療中非常好的動(dòng)物模型。身體質(zhì)量指數(shù)和血糖是常用的糖尿病研究方法。為了建立糖尿病研究的蝙蝠模型,本文探索并建立了蝙蝠的身體質(zhì)量指數(shù)(body mass index,BMI)和前臂長(zhǎng)質(zhì)量指數(shù)(forearm mass index,FMI),并對(duì)這兩個(gè)指數(shù)與血糖水平的相關(guān)性、蝙蝠在急性糖耐量實(shí)驗(yàn)中的表現(xiàn)及其分子機(jī)制進(jìn)行了研究。本研究建立了149種蝙蝠的BMI指數(shù)和860種蝙蝠的FMI指數(shù)。相比較而言,食蟲蝙蝠擁有更低的BMI和FMI,而食果蝙蝠的BMI和FMI更高,雜食蝙蝠、吸血蝙蝠和食肉蝙蝠的BMI和FMI介于食蟲蝙蝠和食果蝙蝠之間,反映了食果蝙蝠比食蟲蝙蝠有更高的正常體重基準(zhǔn)。通過比較,本文發(fā)現(xiàn)人類BMI標(biāo)準(zhǔn)不適合蝙蝠,為此需要建立蝙蝠自身超重和肥胖的判斷標(biāo)準(zhǔn),通過對(duì)雜食蝙蝠在以昆蟲或水果為主要,甚至唯一食物來源時(shí),其BMI和FMI兩指數(shù)和血糖相關(guān)性以及葡萄糖耐量實(shí)驗(yàn)將有助于該標(biāo)準(zhǔn)的確立。隨后對(duì)BMI和FMI指數(shù)與蝙蝠血糖的種間相關(guān)性研究,發(fā)現(xiàn)BMI和FMI指數(shù)與血糖有種間水平的負(fù)相關(guān)性,即擁有較高BMI和FMI值的蝙蝠有較低的血糖水平,而擁有較低BMI和FMI的蝙蝠血糖較高,這與種內(nèi)的BMI與血糖水平的正相關(guān)性不同。針對(duì)這種特別的現(xiàn)象,本文又對(duì)蝙蝠的急性糖耐量實(shí)驗(yàn)進(jìn)行了研究,在對(duì)食果的棕果蝠和食蟲的大蹄蝠的2克葡萄糖耐量實(shí)驗(yàn)中,棕果蝠表現(xiàn)出了更低的空腹血糖、更快速地到達(dá)血糖峰值,更快速地恢復(fù)血糖水平到正常范圍和更小的血糖曲線下面積的特點(diǎn),反映了食果蝙蝠比食蟲蝙蝠更強(qiáng)的維持糖穩(wěn)態(tài)的能力和胰島素降低血糖的能力。血糖可以通過葡萄糖運(yùn)輸?shù)鞍?GLUT)被分別吸收進(jìn)入肝臟、肌肉和脂肪組織,從而降低血糖實(shí)現(xiàn)維持糖穩(wěn)態(tài)的能力。SLC2A2基因的編碼蛋白(GLUT2)是參與調(diào)控葡萄糖進(jìn)出肝臟的關(guān)鍵蛋白。為了研究其在蝙蝠維持糖穩(wěn)態(tài)和胰島素降低血糖過程中的作用,本文進(jìn)一步對(duì)蝙蝠SLC2A2基因在分子進(jìn)化、轉(zhuǎn)錄和翻譯水平的表達(dá)進(jìn)行了研究。其中,對(duì)蝙蝠SLC2A2基因的分子進(jìn)化研究發(fā)現(xiàn),無論是食果蝙蝠、食蟲蝙蝠,還是其各自的祖先進(jìn)化枝,都未檢測(cè)到正選擇作用信號(hào)。然而,在SLC2A2基因啟動(dòng)子區(qū),所有檢測(cè)的食果蝙蝠都缺失了一段長(zhǎng)度為11 bp的核苷酸序列,而該段序列被預(yù)測(cè)為轉(zhuǎn)錄抑制因子ZNF354C的識(shí)別結(jié)合位點(diǎn)。隨后的熒光定量PCR和蛋白質(zhì)雜交實(shí)驗(yàn)證實(shí)缺失該段序列的食果蝙蝠SLC2A2基因在轉(zhuǎn)錄和翻譯水平,都比仍然存在該段序列的食蟲蝙蝠有更高的表達(dá)水平,這可能導(dǎo)致了食果蝙蝠和食蟲蝙蝠糖代謝能力的差別。
[Abstract]:The bat belongs to mammalia Chiroptera species, which accounts for 1/5 of all mammals. Fruit bats than other bats has better maintain glucose homeostasis, insulin sensitivity and insulin hypoglycemic ability, there is a rapid increase in weight in insectivorous bats dormancy, storing large amounts of fat and strong white fat brown like ability, it can become very bat animal model good study and treatment of human diabetes. Body mass index and blood glucose of diabetes is the common research methods. In order to bat model in diabetes research, this paper explores and establishes a body mass index of bats (body mass index, BMI) and forearm length (forearm mass index quality index, FMI), and the correlation of this two index and blood glucose levels, bats in acute glucose tolerance and its molecular mechanism in experimental performance were studied. This study established 149 The bat's BMI index and FMI index of the 860 species of bats. In comparison, insectivorous bats have lower BMI and FMI, while the fruit bat BMI and higher FMI, between the vampire bat and bat omnivorous, carnivorous bat BMI and FMI between insectivorous bats and fruit bats, reflects the fruit eating bat has normal weight higher than the benchmark insectivorous bats. By comparison, this paper found that the human BMI standard is not suitable for bats, this requires the establishment of standards and their fat bat overweight, the bats in omnivorous insects or fruit as the main, or even the only source of food, the BMI and the FMI two index and the correlation between blood glucose and glucose tolerance the establishment of experimental will contribute to this standard. Then the BMI and FMI index and bat blood glucose interspecific correlation study found negative correlation between BMI and FMI index and blood glucose levels between species, which has high BMI and FMI value of the bat There is a low glucose level, while BMI and FMI have lower bat high blood sugar, and this kind of different positive correlation in BMI and the level of blood glucose. In view of this special phenomenon, the acute glucose tolerance test of bats were studied on fruits and large insectivorous bats Hipposideros 2 grams of glucose tolerance test, showed lower Rousettus fasting blood glucose, blood glucose peak arrived more quickly, more quickly to restore blood glucose levels to normal blood glucose curve area and a smaller range of fruit bats reflects stronger than insectivorous bats maintain glucose homeostasis and ability insulin's ability to lower blood sugar. Blood glucose by glucose transport protein (GLUT) were absorbed into the liver, muscle and adipose tissue, thereby reducing the ability of.SLC2A2 gene can maintain glucose homeostasis of blood glucose (GLUT2) encoding protein is involved in the regulation of Key protein import glucose in the liver. In order to study the maintenance of glucose homeostasis and insulin in bat glucose lowering effect in process, in order to bat SLC2A2 gene in molecular evolution, the expression levels of transcription and translation were studied. Among them, the study of molecular evolution of SLC2A2 gene in bats found either frugivorous bats, insectivorous bats still, their ancestral clade, not detected positive selection signal. However, in the promoter region of SLC2A2 gene, all detected fruit bats are missing nucleotide sequence with a length of 11 BP, and the sequence was predicted to identify transcriptional repressor ZNF354C binding sites. Then the fluorescence quantitative PCR and Western blot experiments confirmed that deletion of the sequence of the frugivorous bat SLC2A2 gene on the transcription and translation level than the sequences of insectivorous bats still have higher The expression level, which may lead to the difference between the sugar metabolism of the fruit bats and the insectivorous bats.

【學(xué)位授予單位】：華東師范大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R587.1;R-332

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相關(guān)期刊論文 前2條

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本文編號(hào)：1402350