Effect of hyperosmolality on basal and hormone-stimulated hepatic glucose metabolism in vitro.
To understand better impairment of glucose utilization in diabetics during a hyperosmolal state, in vitro models were established to evaluate the effects of hyperosmolality on basal glucose uptake as well as glucagon dependent glucose release by isolated hepatocytes. In these studies simulating a hyperglycaemic (40 mmol glucose) and hyperosmolal (up to 500 mosm kg-1, NaCl as added solute) state basal hepatic glucose uptake was reversibly suppressed by 19% when osmolality was increased by as little as 10 mosm kg-1. No such effects on glucose uptake by isolated hepatocytes could be attained when the incubation's fluid osmolality was augmented by the addition of urea or mannitol. Estimations of the transport rates of 3-O-methylglucose and uptake of 2-deoxyglucose at 400 vs. 300 mosm kg-1 revealed that impaired intracellular enzymatic activity but not the transport rate of glucose into the cell were responsible for the hyperosmolal defect as uptake was more reduced (P less than 0.025) by increased osmolality for 2-deoxyglucose (16%) than for 3-O-methylglucose (13%). Glucagon dependent glucose release from isolated hepatocytes was diminished by 17.8% when the osmolality was raised to 400 mosm kg-1 by NaCl as added solute. These data obtained in vitro support the clinical contention that a hyperosmolal state, which corresponds to a loss of fluid in excess of solutes, is able to impair basal hepatic glucose uptake as well as glycogenolytic glucagon action on the liver.
Komjati
M
M
I. Medizinische Universitätsklinik, Division of Clinical Endocrinology and Diabetology, Wien, Austria.
Kastner
G
G
Waldhäusl
W
W
Bratusch-Marrain
P
P
D019325:3-O-Methylglucose; D000818:Animals; D003847:Deoxyglucose / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D009994:Osmolar Concentration; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains
D008757:Methylglucosides; D019325:3-O-Methylglucose; D005934:Glucagon; D003847:Deoxyglucose; D005947:Glucose