Porphyromonas gingivalis lipopolysaccharide upregulates insulin secretion from pancreatic β cell line MIN6.
Porphyromonas gingivalis lipopolysaccharide upregulates insulin secretion from pancreatic β cell line MIN6.
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卟啉单胞菌脂多糖上调了胰腺β细胞系Min6的胰岛素分泌。
DOI：
10.1902/jop.2014.140070
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发表时间：
2014-11
影响因子：
4.3
通讯作者：
Watanabe K
中科院分区：
文献类型：
--
作者：
Bhat UG;Ilievski V;Unterman TG;Watanabe K
牙周炎和糖尿病之间的密切联系已在人类横断面研究中得到证实，但牙周炎和糖尿病前期之间的确切关系尚未建立。先前使用动物模型系统的研究一致表明，与牙周组织健康的动物相比，牙周炎动物中发生高胰岛素血症（同时保持正常血糖）。由于细菌脂多糖（LPS）在牙周炎的发病机制中起重要作用，我们推测LPS可能通过直接影响β细胞功能来刺激胰岛素分泌。为了验证这一假设，使用胰腺β细胞系MIN 6细胞来确定牙龈卟啉单胞菌（Pg）LPS对胰岛素分泌的影响。此外，在先天免疫和胰岛素信号通路中，确定了Pg LPS改变的基因表达。MIN 6细胞在具有葡萄糖浓度正常的葡萄糖（5.5mM）的培养基中生长。将Pg LPS以50、200和500 ng/mL的最终浓度加入每个孔中。采用酶联免疫吸附试验测定胰岛素分泌。通过聚合酶链反应（PCR）阵列测定Pg LPS改变的基因表达水平，用于小鼠先天性和适应性免疫应答以及小鼠胰岛素信号传导途径，并通过定量PCR确认特定感兴趣基因的结果。在血糖正常的条件下，Pg LPS刺激胰岛素分泌1.5- 3.0倍，这取决于LPS的浓度。Pg LPS处理改变了参与先天性和适应性免疫应答以及胰岛素信号通路的几个基因的表达。Pg LPS使免疫应答相关基因分化簇8a（Cd 8a）、Cd 14和细胞间粘附分子1（Icam 1）的表达上调约2倍。LPS还增加了两个胰岛素信号相关基因的表达，葡萄糖-6-磷酸酶催化亚基（G6 pc）和胰岛素样3（Insl 3），三到四倍。我们首次证实Pg LPS刺激胰腺β细胞系MIN细胞分泌胰岛素。Pg LPS可能对牙周炎患者糖尿病前期β细胞代偿和胰岛素抵抗的发展具有重要意义。
A close association between periodontitis and diabetes has been demonstrated in human cross-sectional studies, but an exact relationship between periodontitis and prediabetes has not been established. Previous studies using animal model systems consistently have shown that hyperinsulinemia occurs in animals with periodontitis compared to animals with healthy periodontium (while maintaining normoglycemia). Because bacterial lipopolysaccharide (LPS) plays an important role in the pathogenesis of periodontitis, we hypothesized that LPS may stimulate insulin secretion through a direct effect on β cell function. To test this hypothesis, pancreatic β cell line MIN6 cells were used to determine the effect of Porphyromonas gingivalis (Pg) LPS on insulin secretion. Furthermore, expression of genes altered by Pg LPS in innate immunity and insulin-signaling pathways was determined. MIN6 cells were grown in medium with glucose concentration of normoglycemia (5.5 mM). Pg LPS was added to each well at final concentrations of 50, 200, and 500 ng/mL. Insulin secretion was measured using enzyme-linked immunosorbent assay. Gene expression levels altered by Pg LPS were determined by polymerase chain reaction (PCR) array for mouse innate and adaptive immunity response and mouse insulin-signaling pathways, and results were confirmed for specific genes of interest by quantitative PCR. Pg LPS stimulated insulin secretion in the normoglycemic condition by ≈1.5- to 3.0-fold depending on the concentration of LPS. Pg LPS treatment altered the expression of several genes involved in innate and adaptive immune response and insulin-signaling pathway. Pg LPS upregulated the expression of the immune response–related genes cluster of differentiation 8a (Cd8a), Cd14, and intercellular adhesion molecule-1 (Icam1) by about two-fold. LPS also increased the expression of two insulin signaling–related genes, glucose-6-phosphatase catalytic subunit (G6pc) and insulin-like 3 (Insl3), by three- to four-fold. We have demonstrated for the first time that Pg LPS stimulates insulin secretion by pancreatic β cell line MIN cells. Pg LPS may have significant implications on the development of β cell compensation and insulin resistance in prediabetes in individuals with periodontitis.
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影响因子：
7.7
作者：
Cani, Patrice D.;Amar, Jacques;Burcelin, Remy
通讯作者：
Burcelin, Remy
影响因子：
8.2
作者：
Babaya, N;Nakayama, M;Eisenbarth, GS
通讯作者：
Eisenbarth, GS
DOI：
10.1073/pnas.0932778100
发表时间：
2003-07-08
影响因子：
11.1
作者：
Lieberman, SM;Evans, AM;DiLorenzo, TP
通讯作者：
DiLorenzo, TP
影响因子：
4.3
作者：
Maitra, SR;Gestring, ML;Henry, MC
通讯作者：
Henry, MC
影响因子：
2
作者：
Nakashima, Koji;Kanda, Yukiko;Kaku, Kohei
通讯作者：
Kaku, Kohei