Connexin-36 gap junctions regulate in vivo first- and second-phase insulin secretion dynamics and glucose tolerance in the conscious mouse.
Connexin-36 gap junctions regulate in vivo first- and second-phase insulin secretion dynamics and glucose tolerance in the conscious mouse.
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DOI：
10.2337/db11-1312
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发表时间：
2012-07
期刊：
影响因子：
7.7
通讯作者：
Benninger RK
中科院分区：
文献类型：
--
作者：
Head WS;Orseth ML;Nunemaker CS;Satin LS;Piston DW;Benninger RK
胰岛素以协调的脉冲从胰岛分泌。这些脉冲被认为会导致血浆胰岛素振荡，这在降低血糖方面比持续的胰岛素水平更有效。通过连接蛋白-36的β-细胞的间隙连接偶联协调细胞内游离钙振荡和分离的胰岛中的脉动胰岛素释放，然而尚未显示体内作用。我们测试间隙连接偶联的丧失是否会破坏血浆胰岛素振荡，以及这是否会影响葡萄糖耐量。我们描述了连接蛋白36敲除（Cx 36 −/−）小鼠的表型，并在Cx 36 −/−和对照小鼠中快速采集胰岛素进行高血糖钳夹。我们的研究结果表明，Cx 36 −/−小鼠葡萄糖不耐受，尽管正常的血浆胰岛素水平和胰岛素敏感性。然而，Cx 36 −/−小鼠表现出胰岛素脉冲幅度降低和第一时相胰岛素分泌减少。这些变化在孤立的Cx 36 −/−胰岛中也有类似的发现。我们的结论是，Cx 36间隙连接调节体内胰岛素分泌的动力学，这反过来又是重要的葡萄糖稳态。单个胰岛的协调脉动增强胰岛素的第一阶段升高和第二阶段脉冲。由于这些动力学在2型糖尿病的早期阶段被破坏，间隙连接偶联的失调可能是这种疾病发展的重要因素。
Insulin is secreted from the islets of Langerhans in coordinated pulses. These pulses are thought to lead to plasma insulin oscillations, which are putatively more effective in lowering blood glucose than continuous levels of insulin. Gap-junction coupling of β-cells by connexin-36 coordinates intracellular free calcium oscillations and pulsatile insulin release in isolated islets, however a role in vivo has not been shown. We test whether loss of gap-junction coupling disrupts plasma insulin oscillations and whether this impacts glucose tolerance. We characterized the connexin-36 knockout (Cx36−/−) mouse phenotype and performed hyperglycemic clamps with rapid sampling of insulin in Cx36−/− and control mice. Our results show that Cx36−/− mice are glucose intolerant, despite normal plasma insulin levels and insulin sensitivity. However, Cx36−/− mice exhibit reduced insulin pulse amplitudes and a reduction in first-phase insulin secretion. These changes are similarly found in isolated Cx36−/− islets. We conclude that Cx36 gap junctions regulate the in vivo dynamics of insulin secretion, which in turn is important for glucose homeostasis. Coordinated pulsatility of individual islets enhances the first-phase elevation and second-phase pulses of insulin. Because these dynamics are disrupted in the early stages of type 2 diabetes, dysregulation of gap-junction coupling could be an important factor in the development of this disease.
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在四种常用的近交小鼠菌株中的体内葡萄糖代谢。
影响因子：
7.7
作者：
Berglund, Eric D.;Li, Candice Y.;Poffenberger, Greg;Ayala, Julio E.;Fueger, Patrick T.;Willis, Shannon E.;Jewell, Marybeth M.;Powers, Alvin C.;Wasserman, David H.
通讯作者：
Wasserman, David H.
影响因子：
7.7
作者：
BRATUSCHMARRAIN, PR;KOMJATI, M;WALDHAUSL, WK
通讯作者：
WALDHAUSL, WK
影响因子：
7.7
作者：
Nunemaker, CS;Zhang, M;Satin, LS
通讯作者：
Satin, LS
DOI：
10.1152/ajpendo.00498.2002
发表时间：
2003-11-01
影响因子：
5.1
作者：
Lundquist, I;Alm, P;Hellman, B
通讯作者：
Hellman, B
影响因子：
3.4
作者：
Fendler, B.;Zhang, M.;Bertram, R.
通讯作者：
Bertram, R.