Drosophila Models to Investigate Insulin Action and Mechanisms Underlying Human Diabetes Mellitus

Abstract

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.

Keywords: Diabetes; Drosophila; Glucose homeostasis; Insulin-like peptides; Metabolic syndrome models; Type 1 diabetes models; Type 2 diabetes models.