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DOI: 10.1055/s-2000-11003
© Johann Ambrosius Barth
Increase in systolic blood pressure and catecholamine level during hyperinsulinemia in a placebo-controlled euglycemic clamp in healthy subjects
Publication History
Publication Date:
31 December 2000 (online)
Summary:
Hyperinsulinemia has been shown to induce vasodilation and activation of the sympathetic nervous system. Whether these effects result in changes in blood pressure (BP) is discussed controversially. We measured BP and catecholamine levels in 50 healthy subjects during a 40-min baseline phase and during a 100-min euglycemic clamp phase. In a double-blind, between-subject comparison, 30 subjects were infused with 1.5 mU insulin/kg × min, 20 subjects were infused with saline solution. Insulin levels increased during insulin infusion from (mean ± SE) 23.7 ± 0.6 pmol/l to 406.2 ± 3.0 pmol/l, but remained unchanged during placebo infusion. Blood glucose levels were identical during both conditions. Systolic BP increased from 116.6 ± 1.5 mmHg to 119.8 ± 1.8 mmHg during insulin infusion and decreased from 116.6 ± 2.3 mmHg to 114.0 ± 2.4 mmHg during placebo infusion (p < 0.001, for the difference between the effects of insulin vs. placebo). Heart rate was higher during insulin infusion as compared to placebo infusion (63.8 ± 1.9 vs. 60.9 ± 2.4 beats/min, p < 0.05). Norepinephrine levels increased from 1.25 ± 0.09 to 1.58 ± 0.12 nmol/l during insulin infusion and remained unchanged during placebo infusion (1.24 ± 0.09 vs. 1.29 ± 0.11 pmol/l; p < 0.001). Epinephrine levels were also higher during insulin as compared to placebo infusion (249.8 ± 17.4 vs. 212.8 ± 21.1 pmol/l, p < 0.001). The changes did not depend on whether the subject experienced his first or second clamp. Data demonstrate reproducable increasing effects of hyperinsulinemia within the normal physiological range on catecholamine release and systolic BP in healthy humans.
Key words:
Hyperinsulinemia - hypertension - epinephrine - norepinephrine - central nervous effects - healthy subjects
References
- 1 Anderson E A, Hoffmann R P, Balon T W, Sinkey C A, Mark A L. Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans. J Clin Invest. 87 2246-2252 1991;
- 2 Anderson E A, Mark A L. The vasodilator action of insulin. Implications for the insulin hypothesis of hypertension. Hypertension. 21 136-141 1993;
- 3 Azar S T, Birbari A. Nocturnal blood pressure elevation in patients with type 1 diabetes receiving intensive insulin therapy compared with that in patients receiving conventional insulin therapy. J Clin Endocrinol Metab. 83 3190-3193 1998;
- 4 Baron A D, Laakso M, Brechtel G, Edelman S V. Reduced capacity and affinity of skeletal muscle for insulin-mediated glucose uptake in non-insulin-dependent diabetic subjects: effects of insulin therapy. J Clin Invest. 87 1186-1194 1991;
- 5 Berlin I, Grimaldi A, Payan C. Hypoglycemic symptoms and decreased β-adrenergic sensitivity in insulin-dependent diabetic patients. Diabetes Care. 10 742-747 1987;
- 6 Berne C, Fagius J, Pollare T, Hjemdahl P. The sympathetic response to euglycemic hyperinsulinaemia: evidence from microelectrode nerve recordings in healthy subjects. Diabetologia. 35 873-879 1992;
- 7 Bhagat B, Burke W J, Dhalla N S. Insulin-induced enhancement of uptake of noradrenaline in atrial strips. Br J Pharmacol. 74 325-332 1981;
- 8 Carstensen E, Sampson M J, Savage M W, Ware M, Williams G, Yudkin J S. Lack of relationship between sympathetic nervous system activity, measured by two circulating markers, and blood pressure in diabetic and nondiabetic subjects. J Diabetes Complications. 12 140-146 1998;
- 9 Collins V R, Dowse G K, Finch C F, Zimmet P Z. An inconsistent relationship between insulin and blood pressure in three Pacific island populations. J Clin Epidemiol. 43 1369-1378 1990;
- 10 Cruickshanks K J, Orchard T J, Becker D J. The cardiovascular risk profile of adolescents with insulin-dependent diabetes mellitus. Diabetes Care. 8 118-124 1985;
- 11 Davis S N, Colburn C, Dobbins R, Nadeau S, Neal D, Williams P, Cherrington A D. Evidence that the brain of the conscious dog is insulin sensitive. J Clin Invest. 95 593-602 1995;
- 12 Davis S N, Dunham B, Walmsley K, Shavers C, Neal D, Williams P, Cherrington A D. Brain of the conscious dog is sensitive to physiological changes in circulating insulin. Am J Physiol. 272 E567-E575 1997;
- 13 Del Rio G, Baldini A, Carani C, Della Casa L. Adrenomedullary hyperactivity in type I diabetic patients before and during continuous subcutaneous insulin treatment. J Clin Endocrinol Metab. 68 555-559 1989;
- 14 Del Rio G, Marrama P, Della Casa L. High urinary excretion of adrenaline in insulin dependent diabetic subjects. Horm Metab Res. 26 106-108 1992;
- 15 Depres J P, Lamarche B, Mauriege P, Cantin B, Dagenais G R, Moorjani S, Lupin P J. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med. 334 952-957 1996;
- 16 Dieterle P, Fehm H, Ströder W, Henner J, Bottermann P, Schwarz K. Asymptomatic diabetes mellitus in normal weight subjects with hypertension. Studies on glucose tolerance, serum insulin and nonesterified fatty acids in essential hypertension. Dtsch Med Wschr. 52 2376-2381 1967;
- 17 Donahue R P, Orchard T J, Becker D J, Kuller L H, Drash A L. Sex differences in the coronary heart disease risk profile: a possible role for insulin. Am J Epidemiol. 125 650-657 1987;
- 18 Donahue R P, Skyler J S, Schneiderman N, Prineas R J. Hyperinsulinemia and elevated blood pressure: cause, confounder, or coincidence. Am J Epidemiol. 132 827-836 1990;
- 19 Fanelli C, Pampanelli S, Epifano L, Rambotti A M, Ciofetta M, Modarelli F, Di Vincenzo A, Annibale B, Lepore M, Lalli C, Del Sindaco P, Brunetti P, Bolli G B. Relative roles of insulin and hypoglycaemia on induction of neuroendocrine responses to, symptoms of, and deterioration of cognitive function in hypoglycaemia in male and female humans. Diabetologia. 37 797-807 1994;
- 20 Ferrannini E, Buzzigoli G, Bonadonna R, Giorico M A, Oleggini M, Graziadei L, Pedrinelli R, Brandi L, Bevilacqua S. Insulin resistance in essential hypertension. N Engl J Med. 317 350-357 1987;
- 21 Gans R O, v d Toorn L, Bilo H J, Nauta J J, Heine R J, Donker A J. Renal and cardiovascular effects of exogenous insulin in healthy volunteers. Clin Sci. 80 219-225 1991;
- 22 Gundersen H JG, Christensen N J. Intravenous insulin causing loss of intravascular water and albumin and increased adrenergic nervous activity in diabetics. Diabetes. 26 551-557 1977;
- 23 Heller S R, Cryer P E. Reduced neuroendocrine and symptomatic responses to subsequent hypoglycemia after 1 episode of hypoglycemia in nondiabetic humans. Diabetes. 40 223-226 1991;
- 24 Jarret R J. Re: Hyperinsulinemia and elevated blood pressure: cause, confounder, or coincidence. Am J Epidemiol. 134 327-328 1991;
- 25 Julius S. Sympathetic hyperacitvity and coronary risk in hypertension. Hypertension. 21 886-893 1993;
- 26 Laakso M, Edelman S V, Brechtel G, Baron A D. Impaired insulin-mediated skeletal muscle blood flow in patients with NIDDM. Diabetes. 41 1076-1083 1992;
- 27 Lamarche L, Yamaguchi N, Peronnet F, Guitard F. Evidence against a humoral control mechanism in adrenal catecholamine secretion during insulin-induced hypoglycemia. Am J Physiol. 262 659-665 1992;
- 28 Landsberg L, Young J B. Insulin mediated glucose metabolism in the relationship between dietary intake and sympathetic nervous system activity. Int J Obesity. 9 63-68 1985;
- 29 Lembo G, Napoli R, Capaldo B, Rendina V, Iaccarino G, Volpe M, Trimarco B, Sacca L. Abnormal sympathetic overactivity evoked by insulin in the skeletal muscle of patients with essential hypertension. J Clin Invest. 90 24-29 1992;
- 30 Mbanya J N, Thomas T H, Wilkinson R, Alberti K GMM, Taylor R. Hypertension and hyperinsulinaemia: a relation in diabetes but not essential hypertension. Lancet. 1 733-734 1988;
- 31 Mitrakou A, Mokan M, Bolli G, Veneman T, Jenssen T, Cryer P, Gerich J. Evidence against the hypothesis that hyperinsulinemia increases sympathetic nervous systen activity in man. Metabolism. 41 198-200 1992;
- 32 Moan A, Hoieggen A, Nordby G, Birkeland K, Eide I, Kjeldsen S E. The glucose clamp procedure activates the sympathetic nervous system even in the absence of hyperinsulinemia. J Clin Endocrinol Metab. 80 3151-3154 1995;
- 33 Modan M, Halkin H, Almog S, Lusky A, Eshkol A, Shefi M. Hyperinsulinaemia: a link between hypertension, obesity and glucose intolerance. J Clin Invest. 75 809-817 1985;
- 34 Muller D C, Elahi D, Pratley R E, Tobin J D, Andres R. An epidemiological test of the hyperinsulinemia-hypertension hypothesis. J Clin Endocrinol Metab. 76 544-548 1993;
- 35 Muntzel M S, Anderson E A, Johnson A K, Mark A L. Mechanisms of insulin action on sympathetic nerve activity. Clin Exp Hypertens. 17 39-50 1995;
- 36 O'Callaghan C J, Komersova K, Krum H, Louis W J. Physiological hyperinsulinaemia increases distal artery systolic blood pressure without changing proximal blood pressure. Clin Sci. 93 535-540 1997;
- 37 Peters A, Gromeier S, Kohlmann T, Look D, Kerner W. Nocturnal blood pressure elevation is related to adrenomedullary hyperactivity, but not to hyperinsulinemia, in nonobese normoalbuminuric type 1 diabetes. J Clin Endocrinol Metab. 81 507-512 1996;
- 38 Pfeiffer E F, Thum C H, Clemens A H. The artificial beta cell-a continuous control of blood sugar by external regulation of insulin infusion (glucose controlled insulin infusion system). Horm Metab Res. 487 339-342 1974;
- 39 Reaven G M, Hoffman B B. A role for insulin in the aetiology and course of hypertension?. Lancet. 2 435-437 1987;
- 40 Reaven G M, Lithell H, Landsberg L. Hypertension and associated metabolic abnormalities - the role of insulin resistance and the sympathoadrenal system. N Engl J Med. 334 374-381 1996;
- 41 Robertson R P, Halter J B, Porte D J. A role for alpha-adrenergic receptors in abnormal insulin secretion in diabetes mellitus. J Clin Invest. 57 791-795 1976;
- 42 Rowe J W, Young J B, Minaker K L, Stevens A L, Palotta J A, Landsberg L. Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man. Diabetes. 30 219-225 1981;
- 43 Sauter A, Goldstein M, Engel J, Ueta K. Effect of insulin on central catecholamines. Brain Res. 260 330-333 1983;
- 44 Tack C JJ, Smits P, Willemsen J J, Lenders W M, Thien T, Luttermann J A. Effects of insulin on vascular tone and sympathetic nervous system in NIDDM. Diabetes. 45 15-22 1996;
- 45 Van Houten M, Posner B I. Circumventricular organs: receptors and mediators of direct peptide hormone action on brain. Adv Metab Disord. 10 269-289 1983;
- 46 Voigt K H, Ziegler M, Grünert-Fuchs M, Bickel U, Fehm-Wolfsdorf G. Hormonal responses to exhausting physical exercise: The role of predictability and controllability of the situation. Psychoneuroendocrinology. 5 173-184 1990;
- 47 Zadik Z, Kayne R, Kappy M, Plotnick L P, Kowarski A A. Increased integrated concentration of norepinephrine, epinephrine, aldosterone, and growth hormone in patients with uncontrolled juvenile diabetes mellitus. Diabetes. 29 655-658 1980;
- 48 Zietz B, Schäffler R, Büttner R, Schölmerich J, Palitzsch K-D. Elevated levels of leptin and insulin but not of TNF alpha are associated with hypertension in type 2 diabetic males. Exp Clin Endocrinol Diabetes. 108 259-264 2000;
PD Dr. Werner Kern
Medizinische Universität zu Lübeck
Medizinische Klinik I
Ratzeburger Allee 160
D-23538 Luebeck, Germany
Phone: +49-451-5003639
Fax: +49-451-5003640
Email: Kern@kfg.mu-Luebeck.de