The hypothalamic clock and its control of glucose homeostasis

The everyday life of mammals, including humans, exhibits many behavioral, physiological and endocrine oscillations. The major timekeeping mechanism for these rhythms is contained in the central nervous system (CNS). The output of the CNS clock not only controls daily rhythms in sleep/wake (or feeding/fasting) behavior but also exerts a direct control over glucose metabolism. Here, we show how the biological clock plays an important role in determining early morning (fasting) plasma glucose concentrations by affecting hepatic glucose production and glucose uptake, as well as glucose tolerance, by determining feeding-induced insulin responses. Recently, large-scale genetic studies in humans provided the first evidence for the involvement of disrupted (clock gene) rhythms in the pathogenesis of type 2 diabetes.