Effect of Simulated Microgravity on Endocrine Response to Insulin-Induced Hypoglycemia in Physically Fit Men

Abstract

Adaptation to microgravity is associated with alteration in some endocrine functions. In the present longitudinal study, the counterregulatory hormonal response to insulin-induced hypoglycemia (ITT, 0.1 IU/kg short acting insulin i. v.) was evaluated under simulated microgravity conditions in 15 physically fit subjects. ITT was performed at the beginning of the investigation, and again after completion of 6 weeks of endurance training and after a subsequent period of 4 days of head-down bed rest at a backward tilt of 6° from the horizontal. Endurance training showed a significant increase in maximal aerobic capacity in previously well-trained subjects (increase by 12 %), as well as on attenuation of counterregulatory response of epinephrine to hypoglycemia. After 4 days of bed rest, basal concentrations of plasma norepinephrine was diminished (p < 0.002) and plasma renin activity was enhanced (p < 0.02). After bed rest, decreased responses of the two catecholamines (norepinephrine, p < 0.001; epinephrine, p < 0.001), growth hormone (p < 0.001), and cortisol (p < 0.05) were observed. Response of plasma renin activity after bed rest was increased (p < 0.01). This longitudinal study indicated that 4 days of bed rest in endurance-trained subjects induced increased response of PRA to hypoglycemia and attenuation of other counterregulatory neuroendocrine responses.

Key words

Bed Rest - Catecholamines - Adenopituitary Hormones - PRA

References

• 1 Arbeille P H, Gauquelin G, Pottier J M, Pourcelot L, Guell A, Gharib C. Results of a 4-week head down tilt with and without LBNP countermeasure: II. Cardiac and peripheral hemodynamics - comparison with a 25-days spaceflight.  Aviat Space Environ Med. 1992;  63 9-13
• 2 Leach Hunton C S, Grigoriev A L, Natochin Y V. Fluid and electrolyte regulation in spaceflight. San Diego; American Astronautical Society 1998: 81-131
• 3 Hargens A R, Watenpaugh D E. Cardiovascular adaptation to spaceflight.  Med Sci Sports Exerc. 1996;  28 (8) 977-982
• 4 Vernikos J, Dallman M F, Keil L C, O Hara D, Convertino V A. Gender differences in endocrine responses to posture and 7 days of -6 degrees head-down bed rest.  Am J Physiol. 1993;  265 (1 Pt 1) E153-6161
• 5 Sigaudo D, Fortrat J O, Maillet A, Allevard A M, Pavy-Le Traon A, Hughson R L, Guell A, Gharib C, Gauquelin-Koch G. Comparison of 4-day confinement and head-down tilt on endocrine response and cardiovascular variability in humans.  Eur J App Physiol. 1996;  73 28-37
• 6 Pavy-Le Traon A, Louisy F, Vasseur-Clausen P, Guell A, Gharib C. Contributory factors to orthostatic intolerance after simulated weightlessness.  Clinical Physiology. 1999;  19 360-368
• 7 Smorawinski J, Kaciuba-Uscilko H, Nazar K, Kubala P, Kaminska E, Ziemba A W, Adrian J, Greenleaf J E. Effect of three-day bed-rest on metabolic, hormonal and circulatory responses to an oral glucose load in endurance or strength trained athletes an untrained subjects.  J Physiol Pharmacol. 2000;  51 279-289
• 8 Smorawinski J, Nazar K, Kaciuba-Uscilko H, Kaminska E, Cybulski E, Kodrzycka A, Bicz B, Greeleaf J E. Effect of three-day bed-rest on physiological responses to graded exercise in endurance athletes, body builders and sedentary men.  J Appl Physiol. 2001;  91 249-257
• 9 Peuler J D, Johnson G A. Simultaneous single isotope radioenzymatic assay of plasma norepinephrine, epinephrine and dopamine.  Life Sci. 1977;  21 625-636
• 10 Borg W P, Sherwin R S, During M J, Borg M A, Shulman G I. Local ventromedial hypothalamus glucopenia triggers counterregulatory hormone release.  Diabetes. 1995;  44 180-184
• 11 Bolli G B, Fanelli C G. Physiology of glucose counterregulation to hypoglycaemia.  Endocrinology and Metabolism Clinics of North America. 1999;  28 467-492
• 12 Vigas M, Tatar P, Jurcovicova J, Jezova D. Glucoreceptors located in different areas mediate the hypoglycemia-induced release of growth hormone, prolactin and adrenocorticotropin in man.  Neuroendocrinology. 1990;  51 365-368
• 13 Bischof M G, Ludwig C, Hofer A, Kletter K, Krebs M, Stingl H, Nowotny P, Waldhäusl W, Roden M. Hormonal and metabolic counterregulation during and after high-dose insulin-induced hypoglycemia in diabetes mellitus type 2.  Horm Metab Res. 2000;  32 417-423
• 14 Jezova D, Kvetnansky R, Kovacs K, Oprsalova Z, Vigas M, Makara G B. Insulin-induced hypoglycaemia activates the release of adrenocorticotropin predominantly via central and propranolol insensitive mechanisms.  Endocrinology. 1987;  120 409-415
• 15 Hardin D S, Azzarelli B, Edwards J, Wiglesworth J, Maianu L, Brechtel G, Johnson A, Baron A, Garwey W T. Mechanism of enhanced insulin sensitivity in endurance-trained athletes: effects on blood flow and differential expression of GLUT 4 in skeletal muscles.  J Clin Endocrinol Metab. 1995;  80 2437-2446
• 16 Tatar P, Vigas M. Role of alpha 1 and alpha 2 - adrenergic receptors in the GH and prolactin response to insulin-induced hypoglycaemia in man.  Neuroendocrinology. 1984;  39 275-280
• 17 Vukovich M D, Arciero P J, Kohrt W M, Racette S B, Hansen P A, Holloszy J O. Changes in insulin action and GLUT-4 with 6 days of inactivity in endurance runners.  J Appl Physiol. 1996;  80 240-244
• 18 Stallknecht B, Larsen J J, Mikines K J, Simonsen L, Bulow J, Galbo H. Effect of training on insulin sensitivity of glucose uptake and lipolysis in human adipose tissue.  Am J Physiol Endocrinol Metab. 2000;  279 E376-85
• 19 Kjaer M, Farrell P A, Christensen N J, Galbo H. Increased epinephrine responses and inaccurate glycoregulation in exercising athletes. J.  Appl Physiol. 1986;  61 1693-1700
• 20 Kjaer M. Adrenal medulla and exercise training.  Eur J Appl Physiol. 1998;  77 195-199
• 21 Kjaer M, Mikines K J, Christensen N J, Tronier B, Vinten J, Sonne B, Richter E A, Galbo H. Glucose turnover and hormonal changes during insulin-induced hypoglycemia in trained humans.  J Appl Physiol. 1984;  57 21-27
• 22 Convertino V A, Karst G M, Kirby C R, Goldwater D J. Effect of simulated weightlessness on exercise-induced anaerobic threshold.  Aviat Space Environ Med. 1986;  57 325-331
• 23 Tremblay A, Pinsard D, Covenay S, Catellier C, Laferriere G, Richard D, Nadeau A. Counterregulatory response to insulin-induced hypoglycemia in trained and nontrained humans.  Metabolism. 1990;  39 1138-1143
• 24 Greenleaf J E, Vernikos J, Wade C E, Barnes P R. Effect of leg exercise training on vascular volumes during 30 days of 6° head-down bed rest.  J Appl Physiol. 1992;  72 1887-1894
• 25 Goldstein D S, Vernikos J, Holmes C, Convertino V A. Catecholaminergic effect of prolonged head-down bed rest.  J Appl Physiol. 1995;  78 1023-1029
• 26 Vigas M, Kvetnansky R, Jurcovicova J, Jezova D, Tatar P. Comparison of catecholamine and adenopituitary hormone responses to various stress stimuli in man.  In: Stress - The Role of Catecholamines and Other Neurotransmitters. Usdin E, Kvetnansky R, Axelrod J (eds) New York; Gordon and Breach. Sci Pub 1984: 865-882
• 27 Jezova D, Jurankova E, Kvetnansky R, Kaciuba-Uscilko H, Nazar K, Vigas M. Low ambient temperature and neuroendocrine response to hypoglycemia in men.  Obesity Research. 1995;  3 713-719
• 28 Kvetňansk¿ R, Macho l, Koška J, Pacák K, Hoff T, Kšinantová L, Noskov V B, Kobzev E, Grigoriev A I, Vigaš M. Effect of microgravity on plasma catecholamine responses to various stressors during space flight.  J Gravitational Physiol accepted in press.
• 29 Macho L, Koška J, Kšinantová L, Vigaš M, Noskov V B, Grigoriev A I, Kvetňansk¿ R. Plasma hormone levels in human subject during stress loads in microgravity and at readadaptation to earth’s gravity.  J Gravitational Physiol accepted in press.
• 30 Lipman L R, Ulvedal F, Schnure J J, Bradley E M, Lecocq F R. Gluco-regulatory hormone response to 2-deoxy-d-glucose infusion in normal subjects at bedrest.  Metabolism. 1970;  19 980-987
• 31 Kawai Y, Murthy G, Watenpaugh D E, Breit G A, Deroshia C W, Hargens A R. Cerebral blood flow in humans exposed to 24 h of head-down tilt.  J Appl Physiol. 1993;  74 3046-3051
• 32 Frey M A, Mader T H, Bagian J P, Charles J B, Meehan R T. Cerebral blood velocity and other cardiovascular responses to 2 days of head-down tilt.  J Appl Physiol. 1993;  74 319-325
• 33 Chumak O B, Kliueva V N. Specific aspects of the nervous system and brain blood supply in women during prolonged anti-orthostatic hypokinesia.  Aviakosm Ekolog Med. 1999;  33 9-11
• 34 Chaudhuri A, Kanjwal Y, Mohanty P, Rao S, Sung B H, Wilson M F, Dandona P. Insulin-induced vasodilatation of internal carotid artery.  Metabolism. 1999;  48 1470-1473
• 35 Holden R J. The role of brain insulin in the neurophysiology of serious mental disorders.  Med Hypotheses. 1999;  52 193-200