To investigate the effect of acute changes of extracellular osmolality on w
hole body protein and glucose metabolism, we studied 10 male subjects durin
g three conditions: hyperosmolality was induced by fluid restriction and in
travenous infusion of hypertonic NaCl[2-5%; (wt/vol)] during 17 h; hypoosmo
lality was produced by intravenous administration of desmopressin, liberal
water drinking, and infusion of hypotonic saline (0.4%); and the isoosmolal
ity study consisted of ad libitum oral water intake by the subjects. Leucin
e flux ([1-C-13]leucine infusion technique), a parameter of whole body prot
ein breakdown, decreased during the hypoosmolality study (P < 0.02 vs. isoo
smolality). The leucine oxidation rate decreased during the hypoosmolality
study (P < 0.005 vs. isoosmolality). Metabolic clearance rate of glucose du
ring hyperinsulinemic-euglycemic clamping increased less during the hypoosm
olality study than during the isoosmolality study (P < 0.04). Plasma insuli
n decreased, and plasma nonesterified fatty acids, glycerol, and ketone bod
y concentrations and lipid oxidation increased during the hypoosmolality st
udy. It is concluded that acute alterations of plasma osmolality influence
whole body protein, glucose, and lipid metabolism; hypoosmolality results i
n protein sparing associated with increased lipolysis and lipid oxidation a
nd impaired insulin sensitivity.