Loss of renal olfactory receptor 1393 leads to improved glucose homeostasis in a type 1 diabetic mouse model.
Loss of renal olfactory receptor 1393 leads to improved glucose homeostasis in a type 1 diabetic mouse model.
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DOI：
10.14814/phy2.15007
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发表时间：
2021-12
影响因子：
2.5
通讯作者：
Shepard BD
中科院分区：
文献类型：
--
作者：
Schiazza AR;Considine EG;Betcher M;Shepard BD
肾嗅受体1393 （Olfr1393）是一种未被充分研究的感觉受体，它有助于近端小管中的葡萄糖处理。我们之前的研究表明，该受体可能作为葡萄糖钠共转运体（SGLTs）的调节剂，并在饮食诱导的肥胖中促进葡萄糖耐受不良和超滤过的发生。我们假设Olfr1393可能在1型糖尿病中具有类似的功能。利用Olfr1393野生型（WT）和敲除型（KO）小鼠以及链脲佐菌素（STZ）诱导胰腺β细胞耗竭，我们追踪了糖尿病在12周内的发生和进展。在这里，我们报告了患有糖尿病的雄性Olfr1393 KO小鼠在高血糖和葡萄糖耐量方面有显著改善，尽管仍然对STZ敏感。我们还证实Olfr1393定位于肾近端小管，并在肾小球中发现了其他表达。综上所述，这些数据表明，肾脏中Olfr1393的缺失对STZ诱导的1型糖尿病具有保护作用，并且可能是健康和疾病中葡萄糖处理的一般调节因子。我们之前发现嗅觉受体1393在肾近端小管中表达，在那里它有助于葡萄糖稳态。在这里，我们发现这种受体的缺失可以防止1型糖尿病的发生。这项研究增加了对感觉受体在看似非感觉组织中的作用的认识。
Renal olfactory receptor 1393 (Olfr1393) is an understudied sensory receptor that contributes to glucose handling in the proximal tubule. Our previous studies have indicated that this receptor may serve as a regulator of the sodium glucose co‐transporters (SGLTs) and contributes to the development of glucose intolerance and hyperfiltration in the setting of diet‐induced obesity. We hypothesized that Olfr1393 may have a similar function in Type 1 Diabetes. Using Olfr1393 wildtype (WT) and knockout (KO) mice along with streptozotocin (STZ) to induce pancreatic β‐cell depletion, we tracked the development and progression of diabetes over 12 weeks. Here we report that diabetic male Olfr1393 KO mice have a significant improvement in hyperglycemia and glucose tolerance, despite remaining susceptible to STZ. We also confirm that Olfr1393 localizes to the renal proximal tubule, and have uncovered additional expression within the glomerulus. Collectively, these data indicate that loss of renal Olfr1393 affords protection from STZ‐induced type 1 diabetes and may be a general regulator of glucose handling in both health and disease. We previously found that olfactory receptor 1393 is expressed in the renal proximal tubule where it contributes to glucose homeostasis. Here we show that loss of this receptor offers protection from the development of type 1 diabetes. This study adds to the growing appreciation for the roles that sensory receptors play in seemingly non‐sensory tissues.