Insulin signaling is critical for developmental growth and adult homeostasis, yet the downstream regulators of this signaling pathway are not completely understood. Using the model organism Drosophila melanogaster, we took a genomic approach to identify novel mediators of insulin signaling. These studies led to the identification of Meep, encoded by the gene CG32335. Expression of this gene is both insulin receptor- and diet-dependent. We found that Meep was specifically required in the developing fat body to tolerate a high-sugar diet (HSD). Meep is not essential on a control diet, but when reared on an HSD, knockdown of meep causes hyperglycemia, reduced growth, developmental delay, pupal lethality, and reduced longevity. These phenotypes stem in part from Meep’s role in promoting insulin sensitivity and protein stability. This work suggests a critical role for protein homeostasis in development during overnutrition. Because Meep is conserved and obesity-associated in mammals, future studies on Meep may help to understand the role of proteostasis in insulin-resistant type 2 diabetes.

胰岛素信号传导对于发育增长和成人体内稳态至关重要，但该信号传导途径的下游调节因子尚未完全了解。使用模型果蝇果蝇（Drosophila melanogaster），我们采取了基因组方法来鉴定胰岛素信号传导的新型介体。这些研究导致了由基因CG32335编码的Meep的鉴定。该基因的表达是胰岛素依赖性和饮食依赖性的。我们发现，在发育中的脂肪体中特别需要Meep来耐受高糖饮食（HSD）。在控制饮食中，eep不是必不可少的，但在HSD上饲养时，会降低me会导致高血糖，生长减少，发育迟缓、,致死率和寿命降低。这些表型部分源于Meep在促进胰岛素敏感性和蛋白质稳定性方面的作用。这项工作表明蛋白质营养平衡在营养过剩过程中起着至关重要的作用。由于Meep在哺乳动物中是保守的且与肥胖相关，因此对Meep的进一步研究可能有助于了解蛋白稳态在胰岛素抵抗2型糖尿病中的作用。