In higher eukaryotes, nuclear envelope (NE) disassembly allows chromatin to condense and spindle microtubules to access kinetochores. The nuclear lamina, which strengthens the NE, is composed of a polymer meshwork made of A- and B-type lamins. We found that the B-type lamin (Lam) is not fully disassembled and continues to localize along the spindle envelope structure during Drosophila male meiosis I, while the A-type lamin (LamC) is completely dispersed throughout the cytoplasm. Among the nuclear pore complex proteins, Nup107 co-localized with Lam during this meiotic division. Surprisingly, Lam depletion resulted in a higher frequency of cytokinesis failure in male meiosis. We also observed the similar meiotic phenotype in Nup107-depleted cells. Abnormal localization of Lam was found in the Nup-depleted cells at premeiotic and meiotic stages. The central spindle microtubules became abnormal and recruitment of a contractile ring component to the cleavage sites was disrupted in Lam-depleted cells and Nup107-depleted cells. Therefore, we speculate that both proteins are required for a reinforcement of the spindle envelope, which supports the formation of central spindle microtubules essential for cytokinesis in Drosophila male meiosis.

The destruction of pancreatic β cells leads to reduced insulin secretion and eventually causes diabetes. Various types of cellular stress are thought to be involved in destruction and/or malfunction of these cells. We show that endoplasmic reticulum (ER) stress accumulation in insulin-producing cells (IPCs) generated diabeteslike phenotypes in Drosophila. To promote the accumulation of extra ER stress, we induced a dominant-negative form of a Drosophila ER chaperone protein (Hsc70-3 DN) and demonstrate that it causes the unfolded-protein response (UPR) in various tissues. The numbers of IPCs decreased owing to apoptosis induction mediated by caspases. The apoptosis was driven by activation of Dronc, and subsequently by Drice and Dcp-1. Accordingly, the relative mRNA-expression levels of Drosophila insulin-like peptides significantly decreased. Consistent with these results, we demonstrate that glucose levels in larval haemolymph were significantly higher than those of controls. Accumulation of ER stress induced by continuous Hsc70-3 DN expression in IPCs resulted in the production of undersized flies. Ectopic expression of Hsc70-3 DN can induce more efficient ER stress responses and more severe phenotypes. We propose that ER stress is responsible for IPC loss and dysfunction, which results in diabetes-related pathogenesis in this Drosophila diabetes model. Moreover, inhibiting apoptosis partially prevents the ER stress-induced diabetes-like phenotypes.

Diabetes is a group of metabolic diseases in which the patient shows elevated levels of blood sugar. In healthy condition, there is the regulatory system that maintains constant glucose levels in blood. It is accomplished by two hormones, insulin and glucagon acting antagonistically. Insulin is produced in β cells in pancreas and secreted to blood. It specifically binds to its receptors on plasma membrane and activates the intracellular signaling pathways. At the end, glucose in blood are taken into the cells. The diabetes is classified into two types. In type 1 diabetes (T1D), patients' pancreas fails to produce sufficient insulin. Hence, in type 2 diabetes (T2D), the target cells of insulin fail to respond to the hormone. The metabolic syndrome (MS) is characterized as a prediabetes showing lowered responsiveness to insulin. Drosophila has been expected to be a usefulness model animal for the diabetes researches. The regulatory system maintaining homeostasis of circulating sugar in hemolymph is highly conserved between Drosophila and mammals. Here, we summarize findings to date on insulin production and its acting mechanism essential for glucose homeostasis both in mammals and Drosophila. Subsequently, we introduce several Drosophila models for T1D, T2D, and MS. As a consequence of unique genetic approaches, new genes involved in fly's diabetes have been identified. We compare their cellular functions with those of mammalian counterparts. At least three antidiabetic drugs showed similar effects on Drosophila. We discuss whether these Drosophila models are available for further comparative studies to comprehend the metabolic diseases.

Mutations in the insulin gene (INS) are frequently associated with human permanent neonatal diabetes mellitus. However, the mechanisms underlying the onset of this genetic disease is not sufficiently decoded. We induced expression of two types of human mutant INSs in Drosophila using its ectopic expression system and investigated the resultant responses in development. Expression of the wild-type preproinsulin in the insulin-producing cells (IPCs) throughout the larval stage led to a stimulation of the overall and wing growth. However, ectopic expression of human mutant preproinsulins, hINSC96Y and hINSLB15YB16delinsH, neither of which secreted from the β-cells, could not stimulate the Drosophila growth. Furthermore, neither of the mutant polypeptides induced caspase activation leading to apoptosis. Instead, they induced expression of several markers indicating the activation of unfolded protein response, such as ER stress-dependent Xbp1 mRNA splicing and ER chaperone induction. We newly found that the mutant polypeptides induced the expression of Growth arrest and DNA-damage-inducible 45 (Gadd45) in imaginal disc cells. ER stress induced by hINSC96Y also activated the JAK-STAT signaling, involved in inflammatory responses. Collectively, we speculate that the diabetes-like growth defects appeared as a consequence of the human mutant preproinsulin expression was involved in dysfunction of the IPCs, rather than apoptosis.