The purpose of this study
was to investigate the involvement of growth hormone in the diurnal variation
of insulin sensitivity in healthy adults. Afternoon (16:00 hr) or night (23:00
hr) pretreatment with a subcutaneous injection of normal saline, human growth
hormone to mimic the normal nocturnal rise in growth hormone, or octreotide to
inhibit endogenous growth hormone secretion to create a state of relative
nocturnal growth hormone deficiency, was given 16 hours before undergoing the
modified insulin suppression test in healthy subjects. The morning and evening
experiments were separated by an interval of at least 3 days. Thus, each
subject was tested on six separate occasions arranged in a random order. A
higher value of the steady-state plasma glucose (SSPG) is indicative of lower
insulin sensitivity. Plasma glucose, serum insulin, insulin-like growth
factor-1, nonesterified fatty acids (NEFA), and metabolic clearance rate of
insulin (MCRI) were measured. In the normal saline and human growth hormone
groups, SSPG levels were lower in the morning than in the evening. Evening SSPG
levels, MCRI, and NEFA concentrations were higher in the participants treated
with normal saline and growth hormone than in the octreotide group. Differences
in SSPG levels between the morning and evening values were higher in the
participants pretreated with normal saline and growth hormone than in those
treated with octreotide. A diurnal variation in insulin sensitivity existed in
healthy subjects. These results provided direct evidence that the role of
growth hormone in regulating insulin sensitivity might be related to changes in
the MCRI and the metabolism of NEFA in healthy subjects.
References
[1]
Malherbe, C., De Gasparo, M., De Hertogh, R. and Hoet, J.J. (1969) Circadian Variations of Blood Sugar and Plasma Insulin Levels in Man. Diabetologia, 5, 397-404. http://dx.doi.org/10.1007/BF00427978
[2]
Whichelow, M.J., Sturge, R.A., Keen, H., Jarrett, R.J., Stimmler, L. and Grainger, S. (1974) Diurnal Variation in Response to Intravenous Glucose. British Medical Journal, 1, 488-491. http://dx.doi.org/10.1136/bmj.1.5906.488
[3]
Wu, M.S., Ho, L.T., Jap, T.S., Kwok, C.F. and Chen, J.J. (1986) Diurnal Variation of Insulin Clearance and Sensitivity in Normal Man. Proceedings of the National Science Council, Republic of China, Part B, Life Sciences, 10, 64-69.
[4]
Bolli, G.B., De Feo, P., De Cosmo, S., Perriello, G., Ventura, M.M., Calcinaro, F., Lolli, C., Campbell, P., Brunetti, P. and Gerich, J.E. (1984) Demonstration of a Dawn Phenomenon in Normal Human Volunteers. Diabetes, 33, 1150-1153. http://dx.doi.org/10.2337/diab.33.12.1150
[5]
Nielsen, M.F., Dinneen, S., Basu, A., Basu, R., Alzaid, A. and Rizza, R.R. (1998) Failure of Nocturnal Changes in Growth Hormone to Alter Carbohydrate Tolerance the Following Morning. Diabetologia, 41, 1064-1072.
http://dx.doi.org/10.1007/s001250051031
[6]
Fineberg, S. and Merimee, T.J. (1974) Acute Metabolic Effects of Human Growth Hormone. Diabetes, 23, 499-504.
http://dx.doi.org/10.2337/diab.23.6.499
[7]
Sassin, J.F., Parker, D.C., Mace, J.W., Gotlin, R.W., Johnson, L.C. and Rossman, L.G. (1969) Human Growth Hormone Release: Relation to Slow-Wave Sleep and Sleep-Walking Cycles. Science, 165, 513-515.
http://dx.doi.org/10.1126/science.165.3892.513
[8]
Campbell, P.J., Bolli, G.B., Cryer, P.E. and Gerich, J.E. (1985) Pathogenesis of the Dawn Phenomenon in Patients with Insulin-Dependent Diabetes Mellitus. Accelerated Glucose Production and Impaired Glucose Utilization Due to Nocturnal Surges in Growth Hormone Secretion. New England Journal of Medicine, 312, 1473-1479.
http://dx.doi.org/10.1056/NEJM198506063122302
[9]
Hwu, C.M., Kwok, C.F., Lai, T.Y., Shih, K.C., Lee, T.S., Hsiao, L.C., Lee, S.H., Fang, V.S. and Ho, L.T. (1997) Growth Hormone (GH) Replacement Reduces Total Body Fat and Normalizes Insulin Sensitivity in GH-Deficient Adults: A Report of One-Year Clinical Experience. The Journal of Clinical Endocrinology and Metabolism, 82, 3285-3292. http://dx.doi.org/10.1210/jc.82.10.3285
[10]
Shih, K.C., Ho, L.T., Kou, H.F., Liu, P.C., Hsiao, L.C., Li, S.H., Liu, Y.F. and Wu, M.S. (1992) Diurnal Variation in Insulin Sensitivity in NIDDM Patients and Normal Subjects. Journal of the Formosan Medical Association, 91, 263-269.
[11]
Yalow, R.S., Goldsmith, S.J. and Berson, S.A. (1969) Influence of Physiologic Fluctuations in Plasma Growth Hormone on Glucose Tolerance. Diabetes, 18, 402-408. http://dx.doi.org/10.2337/diab.18.6.402
[12]
Hartman, M.L., Faria, A.C., Vance, M.L., Johnson, M.L., Thorner, M.O. and Veldhuis, J.D. (1991) Temporal Structure of in Vivo Growth Hormone Secretory Events in Humans. American Journal of Physiology, 260, E101-E110.
[13]
Butler, P., Kryshak, E. and Rizza, R. (1991) Mechanism of Growth Hormone-Induced Postprandial Carbohydrate Intolerance in Humans. American Journal of Physiology, 260, E513-E520.
[14]
Ho, L.T., Chang, Z.Y., Wang, J.T., Li, S.H., Liu, Y.F., Chen, Y.D. and Reaven, G.M. (1990) Insulin Insensitivity in Offspring of Parents with Type 2 Diabetes Mellitus. Diabetic Medicine, 7, 31-34.
http://dx.doi.org/10.1111/j.1464-5491.1990.tb01303.x
[15]
Noma, A., Okabe, H. and Kita, M. (1973) A New Colorimetric Micro-Determination of Free Fatty Acids in Serum. Clinica Chimica Acta, 43, 317-320. http://dx.doi.org/10.1016/0009-8981(73)90468-3
[16]
MacGorman, L.R., Rizza, R.A. and Gerich, J.E. (1981) Physiological Concentrations of Growth Hormone Exert Insulin-Like and Insulin Antagonistic Effects on Both Hepatic and Extrahepatic Tissues in Man. The Journal of Clinical Endocrinology and Metabolism, 53, 556-559. http://dx.doi.org/10.1210/jcem-53-3-556
[17]
Shih, K.C., Hsieh, S.H., Kwok, C.F., Hwu, C.M., Hsieh, P.S. and Ho, L.T. (2013) Effect of Growth Hormone on Dawn Phenomenon in Patients with Type 2 Diabetes. Growth Factors, 31, 66-73.
http://dx.doi.org/10.3109/08977194.2013.772996
[18]
Shih, K.C., Liu, L.Y., Kwok, C.F., Hwu, C.M., Juan, C.C., Hsu, Y.P. and Ho, L.T. (2007) Effect of Reversing Dark-Light Cycles on Normal Diurnal Variation and Related Metabolic Disturbance in Rats. Chinese Journal of Physiology, 50, 69-76.
[19]
Lindberg-Larsen, R., M?ller, N., Schmitz, O., Nielsen, S., Andersen, M., Orskov, H. and J?rgensen, J.O. (2007) The Impact of Pegvisomant Treatment on Substrate Metabolism and Insulin Sensitivity in Patients with Acromegaly. The Journal of Clinical Endocrinology and Metabolism, 92, 1724-1728. http://dx.doi.org/10.1210/jc.2006-2276
[20]
Campbell, P.J., Bolli, G.B. and Gerich, J.E. (1988) Prevention of the Dawn Phenomenon (Early Morning Hyperglycemia) in Insulin Dependent Diabetes Mellitus by Bedtime Intranasal Administration of Long Acting Somatostatin Analog. Metabolism, 37, 34-37. http://dx.doi.org/10.1016/0026-0495(88)90026-1
[21]
M?ller, N. and Jorgensen, J.O. (2009) Effects of Growth Hormone on Glucose, Lipid and Protein Metabolism in Human Subjects. Endocrine Reviews, 30, 152-177. http://dx.doi.org/10.1210/er.2008-0027
[22]
Krusenstjerna-Hafstr?m, T., Clasen, B.F., M?ller, N., Jessen, N., Pedersen, S.B., Christiansen, J.S. and J?rgensen, J.O. (2011) Growth Hormone (GH)-Induced Insulin Resistance is Rapidly Reversible: An Experimental Study in GH-Deficient Adults. The Journal of Clinical Endocrinology and Metabolism, 96, 2548-2557.
http://dx.doi.org/10.1210/jc.2011-0273
[23]
Perriello, G., De Feo, P., Torlone, E., Fanelli, C., Santeusanio, F., Brunetti, P. and Bolli, G.B. (1990) Nocturnal Spikes of Growth Hormone Secretion Cause the Dawn Phenomenon in Type 1 (Insulin Dependent) Diabetes Mellitus by Decreasing Hepatic (and Extrahepatic) Sensitivity to Insulin in the Absence of Insulin Waning. Diabetologia, 33, 52-59.
http://dx.doi.org/10.1007/BF00586461
[24]
Dux, S., White, N.H., Skor, D.A. and Santiago, J.V. (1985) Insulin Clearance Contributes to the Variability of Nocturnal Insulin Requirement in Insulin-Dependent Diabetes Mellitus. Diabetes, 34, 1260-1265.
http://dx.doi.org/10.2337/diab.34.12.1260
[25]
J?rgensen, J.O. (1991) Human Growth Hormone Replacement Therapy: Pharmacological and Clinical Aspects. Endocrine Reviews, 2, 189-207. http://dx.doi.org/10.1210/edrv-12-3-189
[26]
Bright, G.M., Melton, T.W., Rogol, A.D. and Reaven, G.M. (1980) Failure of Cortisol Blockade to Inhibit Early Morning Increases in Basal Insulin Requirements in Fasting Insulin-Dependent Diabetics. Diabetes, 29, 662-664.
http://dx.doi.org/10.2337/diab.29.8.662
[27]
Skor, D.A., White, N.H., Thomas, L., Shan, S.D., Cryer, P.E. and Santiago, J.V. (1983) Examination of the Role of the Pituitary-Adrenocortical Axis, Counterregulatory Hormones, and Insulin Clearance in Variable Nocturnal Insulin Requirements in Insulin-Dependent Diabetes. Diabetes, 32, 403-407. http://dx.doi.org/10.2337/diab.32.5.403
[28]
Xu, J. and Messina, J.K. (2009) Crosstalk between Growth Hormone and Insulin Signaling. Vitamins & Hormones, 80, 125-153. http://dx.doi.org/10.1016/S0083-6729(08)00606-7
[29]
Domenici, F.P., Argentino, D.P., Mu?oz, M.C., Miquet, J.G., Sotelo, A.I. and Turyn, D. (2005) Influence of the Crosstalk between Growth Hormone and Insulin Signaling on the Modulation of Insulin Sensitivity. Growth Hormone & IGF Research, 15, 324-336. http://dx.doi.org/10.1016/j.ghir.2005.07.001
