Insulin action and hepatic glucose cycling in essential hypertension

Abstract

Peripheral insulin resistance is a feature of essential hypertension, but there is little information about hepatic insulin sensitivity. To investigate peripheral and hepatic insulin sensitivity and activity of the hepatic glucose/glucose 6-phosphate (G/G6P) substrate cycle in essential hypertension, euglycemic glucose clamps were performed in eight untreated patients and eight matched controls at insulin infusion rates of 0.2 and 1.0 mU · kg −1 · min −1. A simultaneous infusion of (2 3H)- and (6 3H)glucose, combined with a selective detritiation procedure, was used to determine glucose turnover, the difference being G/G6P cycle activity. Endogenous hepatic glucose production (EGP) determined with (6 3H)glucose was similar in hypertensive and control groups in the postabsorptive state (11.0 ± 0.3 v 10.9 ± 0.3 μmol · kg −1 · min −1) and with the 0.2 mU insulin infusion (4.9 ± 0.5 v 4.0 ± 0.8 μmol · kg −1 · min −1). With the 1.0 mU insulin infusion, glucose disappearance determined with (6 3H)glucose was lower in the hypertensive group (21.8 ± 2.4 v 29.9 ± 2.4 μmol · kg −1 · min −1, P < .001). G/G6P cycle activity was similar both in the postabsorptive state (2.2 ± 0.4 v 2.7 ± 0.4 μmol · kg −1 · min −1) and during insulin infusion (0.2 mU, 2.5 ± 0.3 v 2.9 ± 0.4; 1.0 mU, 4.7 ± 0.3 v 5.3 ± 1.1 μmol · kg −1 · min −1, for hypertensive and control groups, respectively). Following 12 weeks' therapy with cyclopenthiazide 500 μg/d in the hypertensive group, there were increases in fasting glucose (5.2 ± 0.2 to 5.6 ± 0.2 mmol · L −1, P < .05), fasting insulin (8.5 ± 1.8 to 11.1 ± 3.1 mU · L −1, P < .05), and postabsorptive endogenous glucose production (11.0 ± 0.3 to 12.3 ± 0.4 μmol · kg −1 · min −1, P < .05). EGP during the 0.2-mU infusion and glucose turnover with the 1.0-mU infusion did not change. In conclusion, peripheral but not hepatic insulin sensitivity is diminished in essential hypertension. Activity of the G/G6P substrate cycle is similar in hypertensive and control groups. Cyclopenthiazide therapy causes postabsorptive hyperglycemia, but insulin sensitivity is not affected during hyperinsulinemia.