Animal and human tissue Na,K-ATPase in obesity and diabetes: A new proposed enzyme regulation

Am J Med Sci. 2007 Jan;333(1):1-9. doi: 10.1097/00000441-200701000-00001.


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%).

Conclusion: 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.

MeSH terms

  • Adipose Tissue / enzymology
  • Aged
  • Animals
  • Blood Pressure
  • Diabetes Mellitus, Experimental / enzymology*
  • Female
  • Humans
  • Hyperglycemia / enzymology
  • Hyperinsulinism / enzymology*
  • Insulin / blood
  • Insulin / metabolism
  • Kidney / enzymology
  • Liver / enzymology
  • Male
  • Mice
  • Mice, Obese
  • Middle Aged
  • Obesity / enzymology*
  • Sodium-Potassium-Exchanging ATPase / analysis
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors
  • Sodium-Potassium-Exchanging ATPase / metabolism*


  • Insulin
  • Sodium-Potassium-Exchanging ATPase