Animal and human tissue Na,K-ATPase in obesity and diabetes: A new proposed enzyme regulation.
BACKGROUND
Na,K-ATPase is a membrane enzyme that energizes the Na-pump, hydrolyzing ATP and wasting energy as heat. It may play a role in thermogenesis, energy balance, and obesity development. Regulation of the enzyme by insulin is controversial.


METHODS
In animal and human obesity, tissue Na,K-ATPase was assayed by colorimetric measurement of released Pi.


RESULTS
Na,K-ATPase of hyperglycemic-hyperinsulinemic ob/ob mice (compared with lean control animals) was reduced in liver (-63%) and in kidney (-47%) (P < 0.001 in both instances). In contrast, in streptozotocin-treated hypoinsulinemic-diabetic Swiss mice, versus untreated animals, we found an increase of liver (+54%, P < 0.01) and kidney (+94%, P < 0.001) Na,K-ATPase. The enzyme was also increased (+99%, P < 0.05) in kidney from ob/ob mice made diabetic-hypoinsulinemic with streptozotocin (versus untreated obese animals). This is contrary to the occurrence of a genetic enzymatic defect and suggests regulation by hyperinsulinemia, present in ob/ob mice. A positive correlation between tissue enzyme activity and glycemia existed in both ob/ob and Swiss mice. In adipose tissue from obese patients (compared with lean subjects), Na,K-ATPase was reduced (-65%, P < 0.001) and negatively correlated with body mass index, oral glucose tolerance test-insulinemic area, and mean blood pressure. In vitro, in human liver tissue, 3 mug/mL glucagon exerted a statistically inhibitory effect on Na,K-ATPase (-44%).


CONCLUSIONS
We hypothesize that animal and human obesity is associated with reduction of tissue Na,K-ATPase, linked to hyperinsulinemia, which may repress or inactivate the enzyme, influencing thermogenesis and energy balance.
Iannello
Silvia
S
Department of Internal Medicine and Systemic Pathology, University of Catania Medical School, Ospedale Garibaldi, Catania, Italy.
Milazzo
Paolina
P
Belfiore
Francesco
F
D000273:Adipose Tissue / Q000201:enzymology; D000368:Aged; D000818:Animals; D001794:Blood Pressure; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000201:enzymology; D006946:Hyperinsulinism / Q000201:enzymology*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D008875:Middle Aged; D009765:Obesity / Q000201:enzymology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*
D007328:Insulin; D000254:Sodium-Potassium-Exchanging ATPase