Lifestyle diseases including type 2 diabetes are increasing due to hyperphagia and a lack of exercise, which lead to excess weight and obesity. The body does not respond properly to insulin secreted by the pancreas in type 2 diabetes, a condition known as insulin resistance. Adipokines, which play an important role in saccharometabolism, are secreted by adipocytes, and they maintain the homeostasis of glycolipid metabolism and the vascular wall. Type 2 diabetes appears as a result of an imbalance of adipokine expression due to the accumulation of adipose tissue through lifestyle disorders (Fig. 1). Arteriosclerosis is often caused by diabetes which increases the risk of heart attack, stroke, retinopathy, kidney failure, and nerve dysfunction. These diseases are obstacles to the patient's quality of life, and the cost of medical treatment for these diseases is huge. At least 7 million people in Japan suffer from diabetes and 13 million people have impaired glucose tolerance, which is thought to be a pre-diabetic state. Since the number of patients is increasing, lifestyle improvements are necessary together with accurate estimations of the risk of diabetes to prevent its onset. For this purpose, we are developing a device that can be used for the comprehensive and continuous examination of expression of several adipokines to analyze the robustness of saccharometabolism.
In obesity, adipocytes secrete adipokines such as TNF-α, IL-6, adiponectin, leptin, and hsCRP. We have selected these adipokines as target markers. Adiponectin improves insulin sensitivity by enhancing glucose uptake into skeletal muscle and inhibiting hepatic glucose production. TNF-α and adiponectin suppress each other in expression at the transcriptional level. TNF-α exacerbates insulin tolerance. On the other hand, adiponectin suppresses insulin tolerance. Leptin, whose production is upregulated in large adipocytes, decreases hunger and stimulates energy expenditure. IL-6 is an inflammatory cytokine, like TNF-α. hsCRP is known as a biomarker for inflammation, and exacerbates arteriosclerosis. We will also examine the production of some oxidative stress markers that are thought to be correlated to the onset of diabetes, such as t-HODE, which was discovered by AIST. We will comprehensively and continuously examine the changes in expression of these biomarkers in people who exhibit impaired glucose tolerance, and estimate the usefulness of these changes as biomarkers for pre-disease states. For the examination of these changes, we are developing a sandwich ELISA (enzyme-linked immunosorbent assay) system on a plastic microchip by combining the advantages of microfluidic channels and inkjet print technology for the immobilization of antibody to reduce the reaction time and reagent consumption of ELISA assays (Fig. 2).