No abstract

OBJECTIVE: Adipose tissue is now considered as an endocrine and secretory organ, and some adipocyte factors are thought to play a major role in the induction of insulin resistance in skeletal muscle. Here we tested the hypothesis that the crosstalk between fat and muscle involves activation of inhibitor kB Kinase (IKK) in the myocytes. MEASUREMENTS: Adipocyte-conditioned culture medium was added to the muscle cells overnight, or human fat and muscle cells were kept in co-culture. Insulin signalling was subsequently analysed in the myocytes. Involvement of IKK was assessed using I229, a highly specific inhibitor of the IKK complex. RESULTS: Adipocyte-conditioned medium strongly inhibited insulin-induced serine phosphorylation of Akt in myocytes with a rapid parallel activation of the nuclear factor kB pathway in these cells. Conditioned medium lacking the perturbation of insulin signalling did not activate NF-kB. Insulin signalling to Akt was completely abrogated under co-culture conditions. The IKK inhibitor I229 did not affect protein expression of Akt, but fully restored insulin action in myocytes subjected to co-culture. CONCLUSION: These data show that the release of fat cell factors may rapidly induce insulin resistance in human skeletal muscle cells. This process appears to be mediated by an IKK/NF-kB dependent pathway. We suggest that inhibitors of IKK would be of use to counteract the negative crosstalk between fat and muscle.

Beginning as early as the mid-4th decade of life, an age-dependent reduction in retinal blood flow has to be considered an essential risk factor for disorders of retinal microcirculation. Blood flow measurements are a valuable, but not the sole criterion of microcirculatory disorders. While in retinal occlusive diseases blood flow is a valuable indicator of the severity of microcirculatory disorders, the latter can also occur in the presence of normal and elevated blood flow values. Shifts of the metabolic activity of the retina and changes in the metabolic activity of the retina and changes in the metabolic conditions have to be taken into account when a clinical interpretation is given.