Effects of Amlodipine on Serum Levels of Adrenal Androgens and Insulin in Hypertensive Men with Obesity

We investigated the effects of the calcium channel blocker amlodipine besilate on serum levels of adrenal androgens and insulin in 20 men with essential hypertension and obesity (age: 51.9 ± 4.7 years, body mass index: 27.7 ± 1.5 kg/m²). All were treated with amlodipine besilate (Norvasc) for 3 months. Blood pressure, fasting plasma glucose (FPG), HbA_1c and serum levels of insulin, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), and lipids were measured before and after a 3-month period. In 10 patients, 75 g oral glucose tolerance test (75 g-OGTT) was also performed. Amlodipine besilate treatment 1) lowered the fasting serum insulin level and total serum insulin level during 75 g-OGTT and 2) increased serum DHEA and DHEA-S levels. No changes in fasting plasma glucose, HbA_1c and serum lipids were observed during treatment. We conclude that amlodipine besilate improves insulin resistance and consequently increases serum DHEA and DHEA-S levels.

Amlodipine - Dehydroepiandrosterone (DHEA) - Dehydroepiandrosterone Sulfate (DHEA-S) - Insulin - Hypertension - Obesity

References:

• 1 Ferrannini E, Buzzigoli G, Bonadonna R, Giorico M A, Oleggini M, Graziadei L, Pedrinelli R, Grandi L, Bevilacqua S. Insulin resistance in essential hypertension.  N Engl J Med. 1987;  317 350-357
• 2 Serrano-Gotarredona J, Escobar-Morreale H F, Sancho J M, Garcia-Robles R. Insulin resistance, dehydroepiandrosterone sulfate and sex hormone-binding globulin in essential hypertension.  Horm Metab Res. 1998;  30 153-157
• 3 Gordon G B, Bush D E, Weisman H F. Reduction of atherosclerosis by administration of dehydroepiandrosterone. A study in the hypercholesterolemic New Zealand white rabbit with aortic intimal injury.  J Clin Invest. 1988;  82 712-720
• 4 Nestler J E, Barlascini C O, Clore J N, Blackard W G. Dehydroepiandrosterone reduces serum low density lipoprotein levels and body fat but does not alter insulin sensitivity in normal men.  J Clin Endocrinol Metab. 1988;  66 57-61
• 5 Coleman D L, Leiter E H, Schwizer R W. Therapeutic effects of dehydroepiandrosterone (DHEA) in diabetic mice.  Diabetes. 1982;  31 830-833
• 6 Nestler J E, Strauss J F. Insulin as an effector of human ovarian and adrenal steroid metabolism.  Endocrinol Metab Clin North Am. 1991;  20 807-823
• 7 Smith S, Ravnikar V A, Barbieri R L. Androgen and insulin response to an oral glucose challenge in hyperandrogenic women.  Fertil Steril. 1987;  48 72-77
• 8 Schriock E D, Buffington C K, Hubert G D, Kurtz B R, Kitabchi A E, Buster J E, Givens J R. Divergent correlations of circulating dehydroepiandrosterone sulfate and testosterone with insulin levels and insulin receptor binding.  J Clin Endocrinol Metab. 1988;  66 1329-1331
• 9 Falcone T, Finegood D T, Fantus I G, Morris D. Androgen response to endogenous insulin secretion during the frequently sampled intravenous glucose tolerance test in normal and hyperandrogenic women.  J Clin Endocrinol Metab. 1990;  71 1653-1657
• 10 Nestler J E, Clore J N, Blackard W G. Dehydroepiandrosterone: the “missing link” between hyperinsulinemia and atherosclerosis?.  FASEB J. 1992;  6 3073-3075
• 11 Pollare T, Lithell H, Berne C. A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension.  N Engl J Med. 1989;  321 868-873
• 12 Beer N A, Jakubowicz D J, Beer R M, Arocha I R, Nestler J E. Effects of nitrendipine on glucose tolerance and serum insulin and dehydroepiandrosterone sulfate levels in insulin-resistant obese and hypertensive men.  J Clin Endocrinol Metab. 1993;  76 178-183
• 13 Beer N A, Jakubowicz D J, Beer R M, Nestler J E. The calcium channel blocker amlodipine raises serum dehydroepiandrosterone sulfate and androstenedione, but lowers serum cortisol, in insulin-resistant obese and hypertensive men.  J Clin Endocrinol Metab. 1993;  76 1464-1469
• 14 Pollare T, Lithell H, Selinus I, Berne C. Application of prazosin is associated with an increase of insulin sensitivity in obese patients with hypertension.  Diabetologia. 1988;  31 415-420
• 15 Berne C, Pollare T, Lithell H. Effects of antihypertensive treatment on insulin sensitivity with special reference to ACE inhibitors.  Diabetes Care. 1991;  14 (Suppl 4) 39-47
• 16 Baron A D, Brechtel G, Wallace P, Edelman S V. Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans.  Am J Physiol. 1988;  255 E769-774
• 17 Draznin B, Sussman K E, Eckel R H, Kao M, Yost T, Sherman N A. Possible role of cytosolic free calcium concentrations in mediating insulin resistance of obesity and hyperinsulinemia.  J Clin Invest. 1988;  82 1848-1852