Impaired Insulin Action on Skeletal Muscle Metabolism in Essential Hypertension

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 17; no. 2; pp. 170 - 178
• Main Authors: Natali, Andrea, Santoro, Donatella, Palombo, Carlo, Cerri, Maurizio, Ghione, Sergio, Ferrannini, Eleuterio
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.02.1991; Hagerstown, MD Lippincott
• Subjects: Adult; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Clinical manifestations. Epidemiology. Investigative techniques. Etiology; Forearm; Glucose Tolerance Test; Humans; Hypertension - metabolism; Insulin - pharmacology; Male; Medical sciences; Middle Aged; Muscles - metabolism; Reference Values; Regression Analysis; Human; Hypertension; Resistance; Pathophysiology; Cardiovascular disease; Glucose; Striated muscle; Metabolism; Essential; Insulin
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.17.2.170

Previous studies have shown that essential hypertension is frequently associated with insulin resistance. The tissues responsible for this metabolic alteration have not been denned. We tested the hypothesis that skeletal muscle is the site of insulin resistance of essential hypertension with the use of the perfused forearm technique. Eight hypertensive (age 42±3 years, body mass index 27±1 kg/m, intra-arterial mean blood pressure 126±4 mm Hg) and seven normotensive (age 48±3 years, body mass index 26±1 kg/m, mean blood pressure 95±4 mm Hg) male volunteers were studied. After glucose ingestion (40 g/m), normal glucose tolerance in the patients was maintained at the expense of a heightened plasma insulin response, suggesting the presence of insulin resistance. During graded, local (intra-arterial) hyperinsulinemia encompassing the physiological range (12-120 milliunits/1), glucose uptake by forearm tissues was significantly (p < 0.03) reduced in the hypertensive subjects as compared with the controls at each of five insulin steps, by 43% on the average. In addition, forearm lactate and pyruvate release were significantly less stimulated in the hypertensive than in the normotensive group (p < 0.01 for both), presumably as a consequence of the decreased glucose influx. Forearm exchange of oxygen, carbon dioxide, lipid substrates (free fatty acids, glycerol, and β-hydroxybutyrate), and potassium were similar in the hypertensive and normotensive groups in the basal state. Insulin had no effect on oxygen consumption, carbon dioxide production, and respiratory quotient in either study group, whereas it stimulated free fatty acids, glycerol, and potassium uptake to the same extent in the hypertensive and normotensive groups. We conclude that the insulin resistance of untreated essential hypertension is present in skeletal muscle, is not secondary to increased fatty substrate use (normal respiratory quotient), and is selective for glucose metabolism. Because forearm substrate oxidation is unaltered, the defect in glucose disposal must predominantly involve glucose conversion into glycogen.