LAUSR

AIMES/INTRODUCTION Understanding morning-evening variation in metabolic state is critical for managing metabolic disorders. We aimed to characterize this variation from the viewpoints of insulin secretion and insulin sensitivity, including their relevance to the circadian rhythm. MATERIALS AND METHODS Fourteen and ten non-diabetic subjects were enrolled, and underwent a 75g oral glucose tolerance test (OGTT) and hyperinsulinemic-euglycemic (HE) clamp study, respectively. Participants completed the OGTT or HE clamp at 8 a.m. and 8 p.m. in random order. Prior to each study, hair follicles were collected. In mice, phosphorylation levels of AKT were examined in liver and muscle by western blotting. RESULTS Glucose tolerance was better at 8 a.m., which was explained by the heigher one-hour insulin secretion on OGTT and increased skeletal muscle insulin sensitivity on HE clamp. Hepatic insulin sensitivity, estimated by the hepatic insulin resistance index on OGTT, was better at 8 p.m.. One-hour insulin secretion and the hepatic insulin resistance index correlated significantly with Per2 mRNA expression. Δ (evening value - morning value) GIR correlated significantly with Δ non-esterified fatty acid (NEFA), but not with clock gene expressions. Δ NEFA correlated significantly with E4bp4 mRNA expression and Δ cortisol. In mice, phosphorylation of AKT was decreased in liver and increased in muscle in the beginning of the active period as expected from human study. CONCLUSIONS Glucose metabolism in each tissue differed between morning and evening, partly reflecting lipid metabolism, clock genes, and cortisol levels. Deeper knowledge of these associations might be useful for ameliorating metabolic disorders.