Exp Clin Endocrinol Diabetes 2019; 127(08): 505-510
DOI: 10.1055/a-0597-8985
Article
© Georg Thieme Verlag KG Stuttgart · New York

The Effect of the Oral Administration of Leucine on Endothelial Function, Glucose and Insulin Concentrations in Healthy Subjects

Georgia Argyrakopoulou
1   First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
,
Paraskevi Kontrafouri
1   First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
,
Ioanna Eleftheriadou
1   First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
,
Alexander Kokkinos
1   First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
,
Christina Arapostathi
1   First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
,
Despoina Kyriaki
1   First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
,
Despoina Perrea
2   Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, Athens, Greece
,
Constantinos Revenas
3   Department of Radiology, Laiko General Hospital, Athens, Greece
,
Nicholas Katsilambros
1   First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
,
Nicholas Tentolouris
1   First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
› Author Affiliations
Further Information

Publication History

received 05 December 2017
revised 18 March 2018

accepted 26 March 2018

Publication Date:
11 June 2018 (online)

Abstract

Objective The aim of our study was to investigate the potential differential effect of hyperglycaemia and hyperinsulinaemia induced by glucose infusion alone and in combination with leucine consumption on endothelial function in healthy individuals.

Methods Ten male volunteers were examined in random order twice. In one visit, they consumed 250 ml water (baseline) and 30 min later glucose was infused iv. In the other visit, they consumed 250 ml water with 25 g of leucine and 30 min later the same amount of glucose was infused. Serum glucose and insulin were measured at baseline and every 10 min after glucose infusion for 1 h. Endothelial function was evaluated by measurement of flow mediated vasodilatation (FMD) at baseline, 10 and 60 min after glucose infusion.

Results In both visits, glucose levels increased to the same degree, whereas insulin response was significantly higher after leucine administration. FMD values declined significantly compared to baseline 10 min after glucose infusion in the control visit (6.9±2.7 vs. 3.2±3.5%, respectively, p=0.006), while no significant change was observed when glucose infusion was followed by leucine consumption.

Conclusions Acute hyperglycaemia impairs endothelial function in healthy male individuals. Leucine administration prevents hyperglycaemia-mediated endothelial dysfunction probably due to enhanced insulin secretion.

Deceased


 
  • References

  • 1 Nair KS, Short KR. Hormonal and signaling role of branched-chain amino acids. J Nutr. 2005; 135: 1547S-1552S
  • 2 van Loon LJ, Saris WH, Verhagen H. et al. Plasma insulin responses after ingestion of different amino acid or protein mixtures with carbohydrate. Am J Clin Nutr. 2000; 72: 96-105
  • 3 van Loon LJ, Kruijshoop M, Menheere PP. et al. Amino acid ingestion strongly enhances insulin secretion in patients with long-term type 2 diabetes. Diabetes Care. 2003; 26: 625-630
  • 4 Manders RJ, Wagenmakers AJ, Koopman R. et al. Co-ingestion of a protein hydrolysate and amino acid mixture with carbohydrate improves plasma glucose disposal in patients with type 2 diabetes. Am J Clin Nutr. 2005; 82: 76-83
  • 5 Yang J, Chi Y, Burkhardt BR. et al. Leucine metabolism in regulation of insulin secretion from pancreatic beta cells. Nutr Rev. 2010; 68: 270-279
  • 6 Loader J, Montero D, Lorenzen C. et al. Acute hyperglycemia impairs vascular function in healthy and cardiometabolic diseased subjects: Systematic review and meta-analysis. Arterioscler Thromb Vasc Biol 2015; 35: 2060-2072
  • 7 Creager MA, Luscher TF, Cosentino F. et al. Diabetes and vascular disease: Pathophysiology, clinical consequences, and medical therapy: Part I. Circulation 2003; 108: 1527-1532
  • 8 Mikhail N, Tuck ML. Insulin and the vasculature. Curr Hypertens Rep. 2000; 2: 148-153
  • 9 Steinberg HO, Baron AD. Vascular function, insulin resistance and fatty acids. Diabetologia 2002; 45: 623-634
  • 10 Arcaro G, Cretti A, Balzano S. et al. Insulin causes endothelial dysfunction in humans: Sites and mechanisms. Circulation 2002; 105: 576-582
  • 11 Campia U, Sullivan G, Bryant MB. et al. Insulin impairs endothelium-dependent vasodilation independent of insulin sensitivity or lipid profile. Am J Physiol Heart Circ Physiol 2004; 286: H76-H82
  • 12 Perkins JM, Joy NG, Tate DB. et al. Acute effects of hyperinsulinemia and hyperglycemia on vascular inflammatory biomarkers and endothelial function in overweight and obese humans. Am J Physiol Endocrinol Metab. 2015; 309: E168-E176
  • 13 Hashimoto M, Akishita M, Eto M. et al. Modulation of endothelium-dependent flow-mediated dilatation of the brachial artery by sex and menstrual cycle. Circulation 1995; 92: 3431-3435
  • 14 Corrado E, Muratori I, Tantillo R. et al. Relationship between endothelial dysfunction, intima media thickness and cardiovascular risk factors in asymptomatic subjects. Int Angiol. 2005; 24: 52-58
  • 15 Corretti MC, Anderson TJ, Benjamin EJ. et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: A report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 2002; 39: 257-265
  • 16 Tabit CE, Chung WB, Hamburg NM. et al. Endothelial dysfunction in diabetes mellitus: Molecular mechanisms and clinical implications. Rev Endocr Metab Disord 2010; 11: 61-74
  • 17 Funk SD, Yurdagul Jr. A, Orr AW. Hyperglycemia and endothelial dysfunction in atherosclerosis: Lessons from type 1 diabetes. Int J Vasc Med 2012; 2012: 569654
  • 18 Sena CM, Pereira AM, Seica R. Endothelial dysfunction – a major mediator of diabetic vascular disease. Biochim Biophys Acta 2013; 1832: 2216-2231
  • 19 Williams SB, Goldfine AB, Timimi FK. et al. Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo. Circulation 1998; 97: 1695-1701
  • 20 Title LM, Cummings PM, Giddens K. et al. Oral glucose loading acutely attenuates endothelium-dependent vasodilation in healthy adults without diabetes: An effect prevented by vitamins C and E. J Am Coll Cardiol 2000; 36: 2185-2191
  • 21 Beckman JA, Goldfine AB, Gordon MB. et al. Ascorbate restores endothelium-dependent vasodilation impaired by acute hyperglycemia in humans. Circulation 2001; 103: 1618-1623
  • 22 Beckman JA, Goldfine AB, Gordon MB. et al. Inhibition of protein kinase Cbeta prevents impaired endothelium-dependent vasodilation caused by hyperglycemia in humans. Circ Res. 2002; 90: 107-111
  • 23 Kawano H, Motoyama T, Hirashima O. et al. Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery. J Am Coll Cardiol. 1999; 34: 146-154
  • 24 Bagg W, Whalley GA, Sathu A. et al. The effect of acute hyperglycaemia on brachial artery flow mediated dilatation in normal volunteers. Aust N Z J Med 2000; 30: 344-350
  • 25 Siafarikas A, Watts K, Beye P. et al. Lack of effect of oral glucose loading on conduit vessel endothelial function in healthy subjects. Clin Sci (Lond) 2004; 107: 191-196
  • 26 Reed AS, Charkoudian N, Vella A. et al. Forearm vascular control during acute hyperglycemia in healthy humans. Am J Physiol Endocrinol Metab. 2004; 286: E472-E480
  • 27 Brownlee M. The pathobiology of diabetic complications: A unifying mechanism. Diabetes 2005; 54: 1615-1625
  • 28 Grover A, Padginton C, Wilson MF. et al. Insulin attenuates norepinephrine-induced venoconstriction. An ultrasonographic study. Hypertension 1995; 25: 779-784
  • 29 Yki-Jarvinen H, Utriainen T. Insulin-induced vasodilatation: Physiology or pharmacology?. Diabetologia 1998; 41: 369-379
  • 30 Hermann TS, Ihlemann N, Dominguez H. et al. Prolonged local forearm hyperinsulinemia induces sustained enhancement of nitric oxide-dependent vasodilation in healthy subjects. Endothelium 2004; 11: 231-239