Animal and human tissue Na,K-ATPase in normal and insulin-resistant states: regulation, behaviour and interpretative hypothesis on NEFA effects.
The sodium(Na)- and potassium(K)-activated adenosine-triphosphatase (Na,K-ATPase) is a membrane enzyme that energizes the Na-pump by hydrolysing adenosine triphosphate and wasting energy as heat, so playing a role in thermogenesis and energy balance. Na,K-ATPase regulation by insulin is controversial; in tissue of hyperglycemic-hyperinsulinemic ob/ob mice, we reported a reduction, whereas in streptozotocin-treated hypoinsulinemic-diabetic Swiss and ob/ob mice we found an increased activity, which is against a genetic defect and suggests a regulation by hyperinsulinemia. In human adipose tissue from obese patients, Na,K-ATPase activity was reduced and negatively correlated with body mass index, oral glucose tolerance test-insulinemic area and blood pressure. We hypothesized that obesity is associated with tissue Na,K-ATPase reduction, apparently linked to hyperinsulinemia, which may repress or inactivate the enzyme, thus opposing thyroid hormones and influencing thermogenesis and obesity development. Insulin action on Na,K-ATPase, in vivo, might be mediated by the high level of non-esterified fatty acids, which are circulating enzyme inhibitors and increase in obesity, diabetes and hypertension. In this paper, we analyse animal and human tissue Na,K-ATPase, its level, and its regulation and behaviour in some hyperinsulinemic and insulin-resistant states; moreover, we discuss the link of the enzyme with non-esterified fatty acids and attempt to interpret and organize in a coherent view the whole body of the exhaustive literature on this complicated topic.
Iannello
S
S
Department of Medicina Interna e Patologie Sistemiche, University of Catania, Ospedale Garibaldi, Catania, Italy.
Milazzo
P
P
Belfiore
F
F
D000273:Adipose Tissue / Q000201:enzymology; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000201:enzymology / Q000378:metabolism; D006946:Hyperinsulinism / Q000201:enzymology / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D009765:Obesity / Q000201:enzymology* / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D000254:Sodium-Potassium-Exchanging ATPase