Detrimental effect of hyperosmolality on insulin-stimulated glucose metabolism in adipose and muscle tissue in vitro.

To better understand impairment of glucose utilization in diabetics during a hyperosmolal state, in vitro models were established to evaluate the interdependence of hyperosmolality on basal as well as insulin-dependent glucose uptake by rat epididymal fat pads and diaphragms. Using the epididymal fat pad it was shown that NaCl and urea induced hyperosmolality of 400 and 500 mOsm/kg diminished insulin-stimulated glucose uptake by 35 and 90%, as well as 29 and 68%, respectively. Using rat diaphragm as target tissue for insulin action instead a transient rise in basal (non-insulin-dependent) glucose uptake was seen at 400 but not at 500 mOsm/kg. Associated impairment of insulin-dependent glucose uptake was 30 and 79%, respectively. These in vitro data support our previous clinical contention that a hyperosmolal state, which corresponds to a loss of fluid in excess of solutes, is able to impair basal glucose utilization as well as hormone action on glucose metabolism.