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Muscle Sodium, Potassium, and [³H]Ouabain Binding in Identical Twins, Discordant for Type 2 Diabetes¹

Departments of Clinical Biochemistry and Genetics (S.D., N.A.H.K.), Cardiology B (S.D.), and Endocrinology M (A.V.), Odense University Hospital, 5000 Odense C; and Steno Diabetes Center (A.V.), 2820 Gentofte, Denmark

Address all correspondence and requests for reprints to: Dr. M. Stig Djurhuus, Svanereden 2, 5270 Odense N, Denmark. E-mail: msd{at}dadlnet.dk

A reduced functional capacity of the sodium (Na), potassium (K) pump might reduce energy expenditure, inducing obesity and type 2 diabetes. Consequently, the Na and K content and [³H]ouabain binding capacity of skeletal muscle were measured in 10 monozygotic twin pairs discordant for type 2 diabetes and in 10 obese controls. Muscle [³H]ouabain binding capacity was reduced by approximately 20% in type 2 diabetes. Removing the genetic component by looking at differences within twin pairs, the difference in waist/hip ratio was associated with the difference in [³H]ouabain binding (r = -0.85; P < 0.002). Except for the type 2 diabetic twins in the basal state, both basal and insulin-stimulated energy expenditure were associated with the muscle K/Na ratio in the twins. In controls, the 2-h plasma glucose concentration during an oral glucose tolerance test was associated with the change in both muscle and plasma K induced by a euglycemic, hyperinsulinemic clamp. In conclusion, environmental factors related to the waist/hip ratio reduce the muscle [³H]ouabain binding capacity in type 2 diabetes. Without proving causality, the muscle K/Na ratio is associated with energy expenditure in individuals genetically predisposed to the development of type 2 diabetes.

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