Department of Biological Sciences, California State University Long Beach, Long Beach, CA 90840, USA.
Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
Int J Mol Sci. 2023 Feb 20;24(4):4185. doi: 10.3390/ijms24044185.
Inositol depletion has been associated with diabetes and related complications. Increased inositol catabolism, via -inositol oxygenase (MIOX), has been implicated in decreased renal function. This study demonstrates that the fruit fly catabolizes -inositol via MIOX. The levels of mRNA encoding MIOX and MIOX specific activity are increased when fruit flies are grown on a diet with inositol as the sole sugar. Inositol as the sole dietary sugar can support survival, indicating that there is sufficient catabolism for basic energy requirements, allowing for adaptation to various environments. The elimination of MIOX activity, via a WH-element inserted into the gene, results in developmental defects including pupal lethality and pharate flies without proboscises. In contrast, RNAi strains with reduced levels of mRNA encoding MIOX and reduced MIOX specific activity develop to become phenotypically wild-type-appearing adult flies. -Inositol levels in larval tissues are highest in the strain with this most extreme loss of -inositol catabolism. Larval tissues from the RNAi strains have inositol levels higher than wild-type larval tissues but lower levels than the WH-element insertion strain. -Inositol supplementation of the diet further increases the -inositol levels in the larval tissues of all the strains, without any noticeable effects on development. Obesity and blood (hemolymph) glucose, two hallmarks of diabetes, were reduced in the RNAi strains and further reduced in the WH-element insertion strain. Collectively, these data suggest that moderately increased -inositol levels do not cause developmental defects and directly correspond to reduced larval obesity and blood (hemolymph) glucose.
肌醇耗竭与糖尿病及其相关并发症有关。通过肌醇氧化酶（MIOX）增加肌醇分解代谢，与肾功能下降有关。本研究表明，果蝇通过 MIOX 分解肌醇。当果蝇在以肌醇为唯一糖的饮食中生长时，编码 MIOX 的 mRNA 水平和 MIOX 特异性活性增加。肌醇作为唯一的膳食糖可以支持生存，表明有足够的分解代谢来满足基本的能量需求，从而能够适应各种环境。通过插入基因中的 WH 元件消除 MIOX 活性，导致发育缺陷，包括蛹致死和无喙的拟蛹。相比之下，RNAi 株中编码 MIOX 的 mRNA 水平降低和 MIOX 特异性活性降低，发育成为表型野生型外观的成年果蝇。在这种最极端的肌醇分解代谢丧失的菌株中，幼虫组织中的肌醇水平最高。与野生型幼虫组织相比，RNAi 株的幼虫组织中的肌醇水平更高，但比 WH 元件插入株的肌醇水平更低。饮食中补充肌醇进一步增加了所有菌株幼虫组织中的肌醇水平，但对发育没有任何明显影响。肥胖和血液（血淋巴）葡萄糖，糖尿病的两个标志，在 RNAi 株中减少，在 WH 元件插入株中进一步减少。总的来说，这些数据表明，适度增加肌醇水平不会导致发育缺陷，并且与减少的幼虫肥胖和血液（血淋巴）葡萄糖直接相关。
