Circulating Blood Glucose and Hypothalamic-Pituitary Secretion

  • M. Grino
  • V. Guillaume
  • A. Caraty
  • B. Conte-Devolx
  • P. Joanny
  • F. Boudouresque
  • G. Pesce
  • J. Steinberg
  • G. Peyre
  • A. Dutour
  • P. Giraud
  • C. Oliver
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 274)


Normally glucose accounts for more than 90% of the metabolic fuel of the brain (1). A constant supply and utilization of glucose is essential for normal cerebral metabolism since brain carbohydrate stores are very small. Hypoglycemia as well as diabetes mellitus result in a variety of neuroendocrine alterations probably through changes in the rate of glucose uptake and metabolism in the hypothalamus. At the hypothalamic-pituitary level, two metabolic conditions can be realized: either increased glucose disposal after administration of exogenous glucose, or glucopenia due to hypoglycemia or diabetes. In the latter condition, blood glucose increased, but cannot be utilized in brain cells because of the lack of insulin secretion. Changes in pituitary hormone release under these acute or chronic alterations in blood glucose levels have been well characterized. However, the role of the hypothalamus in driving these variations in pituitary function is still controversial due to difficulties in measuring the secretion of the hypophysiotropic factors. Therefore, the mechanisms by which hyper-or hypoglycemia exerts an influence on hypothalamic neurons remain to be determined. In this report, we will briefly review this tropic including some results from our laboratory, keeping in mind the potential clinical applications of animal studies.


Thyroid Stimulate Hormone Mediobasal Hypothalamus LHRH Release Thyroid Stimulate Hormone Secretion Hypophysial Portal Blood 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Pardridge, W.B., Brain metabolism. A perspective from the blood-brain barrier,Physiol Rev63: 1481–1535, 1983.PubMedGoogle Scholar
  2. 2.
    Vierhapper, H., B. Grubeck-Loebenstein, P. Bratush-Marrain, S. Panzer, and W. Waldhausl, The impact of euglycemia and hyperglycemia on stimulated pituitary hormone release in insulin-dependent diabetics, JClin Endocrinol Metab52: 1230–1234, 1981.PubMedCrossRefGoogle Scholar
  3. 3.
    Shibasaki, T., A. Masuda, M. Hotta, N. Yamauchi, N. Hizuka, K. Takano, H. Demura, and K. Shizume, Effects of ingestion of glucose on GH and TSH secretion: evidence for stimulation of somatostatin release from the hypothalamus by acute hyperglycemia in normal man and its impairment in acromegalic patients,Life Sci44: 431–438, 1989.PubMedCrossRefGoogle Scholar
  4. 4.
    Ježová-Repβekovác, D., M. Vigaš, and I. Klimeš, Decreased plasma Cortisol response to pharmacological stimuli after glucose load in man,Endocrinol Exp14: 113–120, 1980Google Scholar
  5. 5.
    Bestetti, G.E., M.J. Reymond, I.V. Perrin, P.C. Kniel, T. Lemarchand-Beraud, and G.L. Rossi, Thyroid and pituitary secretory disorders in streptozotocin-diabetic rats are associated with severe structural changes of these glands,Virchows Arch B Cell Pathol53: 69–78, 1987.CrossRefGoogle Scholar
  6. 6.
    Bestetti, G.E., H.P. Jacob, C.E. Boujon, M.J. Reymond, and G.L. Rossi, Le diabète induit par la streptozotocine altère le fonctionnement et la morphologie de 1’hypothalamus médiobasal du rat mâle: étude des axones à TRH dans 1’ éminence médiane à 1’ aide d’ un modèlein vitro, Congrès de la Société de Neuroendocrinologie Exp é rimentale, Anales d’ Endocrinologie,Rennes, September, 1988, p. 15 N.Google Scholar
  7. 7.
    Wilber, J.F., A. Banergi, C. Prasa, and M. Mori, Alterations in hypothalamic pituitary-thyroid regulation produced by diabetes mellitus,Life Sci28: 1757–1763, 1981.PubMedCrossRefGoogle Scholar
  8. 8.
    Tesone, M., R.G. Ladenheim, and E.H. Charreau, Alterations in the prolactin secretion in strep-tozotocin-induced diabetic rats. Correlation with pituitary and hypothalamus estradiol receptors,Mol Cell Endocrinol43: 135–140, 1985.PubMedCrossRefGoogle Scholar
  9. 9.
    Reymond, M.J., and T. Lemarchand-Beraud, Hyperactivity of the hypothalamic dopaminergic neurons and hyposecretion of prolactin in diabetic rats: influence of the thyroid status,8th International Congress of Endocrinology,July 17–23, Kyoto, Japan, Abstract 08-19-045, 1988.Google Scholar
  10. 10.
    Reymond, M.J., and T. Lemarchand-Beraud, Effects of thyroid hormones on the hypothalamic dopaminergic neurons, In J.C. Porter and D. Ježová (eds)Circulating Regulatory Factors and Neuroendocrine Function,Plenum Press, New York, pp.257–270, 1990.Google Scholar
  11. 11.
    Mooradian, A.D., J.E. Morlay, C.J. Billington, M.F. Slag, M.K. Elson, and R.R. Shafer, Hyperprolac-tinoemia in male diabetics,Postgraduate Med J61: 11–14, 1985.CrossRefGoogle Scholar
  12. 12.
    Mooradian, A.D., Diabetic complications of the central nervous system,Endocrine Rev9: 346–356,1988.CrossRefGoogle Scholar
  13. 13.
    L’Age, M., J. Langholz, W. Fechner, and H. Salzman, Disturbances of the hypothalamo-hypophysial-adrenocortical system in the alloxan diabetic rat,Endocrinology95: 760–765,, 1974.PubMedCrossRefGoogle Scholar
  14. 14.
    De Nicola, A.F., O. Fridman, E.J. Del Castillo, and V.G. Foglia, The influence of streptozotocin diabetes on adrenal function in male rats,Horm Metab Res8: 388–392, 1976.PubMedCrossRefGoogle Scholar
  15. 15.
    De Nicola, A.F., O. Fridman, E.J. Del Castillo, and V.G. Foglia, Abnormal regulation of adrenal function in rats with streptozotocin diabetes,Horm Metab Res9: 469–473, 1977.PubMedCrossRefGoogle Scholar
  16. 16.
    Locatelli, V., F. Petraglia, N. Tirloni, and E.E. Müller, Beta-endorphin concentrations in the hypothalamus, pituitary and plasma of streptozotocin-diabetic rats with and without insulin substitution therapy,Life Sci38: 379–386, 1986.PubMedCrossRefGoogle Scholar
  17. 17.
    Brooks, D.P., D.F. Nutting, J.T. Crofton, and L. Share, Vasopressin in rats with genetic and strep-tozotocin-induced diabetes,Diabetes38: 54–57, 1989.PubMedCrossRefGoogle Scholar
  18. 18.
    Thompson, C.J., J. Thow, I.R. Jones, and P.H. Baylis, Vasopressin secretion during insulin-induced hypoglycemia: exaggerated response in people with type 1 diabetes,Diabetic Med6: 158–163, 1989.PubMedCrossRefGoogle Scholar
  19. 19.
    Bestetti, G.E., V. Locatelli, F. Tirone, G.L. Rossi, and E.E. Müller, One month of streptozotocin-diabetes induces different neuroendocrine and morphological alterations in the hypothalamo-pituitary axis of male and female rats,Endocrinology117: 208–216, 1985.PubMedCrossRefGoogle Scholar
  20. 20.
    Bestetti, G.E., C.E. Boujon, M.J. Reymond, and G.L. Rossi, Functional and morphological changes in mediobasal hypothalamus of streptozotocin-induced diabetic rats:in vitrostudy of LHRH release,Diabetes38: 471–476, 1989.PubMedCrossRefGoogle Scholar
  21. 21.
    Conte-Devolx, B., C. Oliver, and J.L. Codaccioni, Diabete et function Leydigienne,Progrès en Andrologie2: 39–45, 1989.Google Scholar
  22. 22.
    Djursing H., C. Hagen, H.C. Hyholm, L. Carstensen, and A.N. Andersen, Gonadotropin responses to gonadotropin-releasing hormone and prolactin responses to thyrotropin-releasing hormone and metoclopramide in women and amenorrhea and insulin-treated diabetes mellitus, JClin Endocrinol Metab56: 1016–1021, 1983.PubMedCrossRefGoogle Scholar
  23. 23.
    Tannenbaum, G.S., Growth hormone secretion dynamics in streptozotocin diabetes: evidence of a role for endogenous-circulating somatostatin,Endocrinology108: 76–82, 1981.PubMedCrossRefGoogle Scholar
  24. 24.
    Tannenbaum, G.S., E. Colle, W. Gurd, and L. Wanamaker, Dynamic time-course studies of the spontaneously diabetic BB Wistar rat. I. Longitudinal profiles of plasma growth hormone, insulin, and glucose,Endocrinology109: 1872–1879, 1981.PubMedCrossRefGoogle Scholar
  25. 25.
    Joanny, P., G. Peyre, J. Steinberg, B. Conte-Devolx, and C. Oliver, Secretion hypothalamique de somatostatine chez les rats diabétiques,Diab è te et Métabolisme(Abstract 76) 14: 168, 1988.Google Scholar
  26. 26.
    Jones, P.M., J.M. Burrin, Y. Yiangou, and S.R. Bloom, Altered synthesis of hypothalamic somatostatin and growth hormone releasing factor may explain growth hormone abnormalities in the streptozotocin diabetic rat,Diabetic Med 5 [Suppl P20],1988.Google Scholar
  27. 27.
    Welsh, J.B., and M. Szabo, Impaired suppression of growth hormone release by somatostatin in cultured adenohypophyseal cells of spontaneously diabetic BB/W rats,Endocrinology123: 2230–2234, 1988.PubMedCrossRefGoogle Scholar
  28. 28.
    Locatelli, V., S. Rovati, H. Miyoshi, and E.E. Müller, Growth hormone hyperresponsiveness to human pancreatic growth hormone releasing hormone in streptozotocin-diabetic rats,Horm Metab Res16: 507, 1984.PubMedCrossRefGoogle Scholar
  29. 29.
    Serri, O., and P. Brazeau, Growth hormone responsivenessin vivoandin vitroto growth hormone releasing factor in the spontaneously diabetic BB Wistar rat,Neuroendocrinology46: 162–166, 1987.PubMedCrossRefGoogle Scholar
  30. 30.
    Müller, E.E., Neural control of somatotropic function,PhysiologRev67: 962–1053, 1987.Google Scholar
  31. 31.
    Hansen, A.P., and K. Johansen, Diurnal pattern of blood glucose, serum free fatty acids, insulin, glucagon and growth hormone in normals and juvenile diabetics,Diabetologia6: 27–33, 1970.PubMedCrossRefGoogle Scholar
  32. 32.
    Press, M., Tamborlane, W.V., and R.S. Sherwin, Importance of raised growth hormone levels in mediating the metabolic derangements of diabetes,N Engl J Med310: 810–815, 1984.PubMedCrossRefGoogle Scholar
  33. 33.
    Holly, J.M.P., S.A. Amiel, R. Sandhu, L.H. Rees, and J.A.H. Wass, The role of growth hormone in diabetes mellitus, JEndocrinology118: 353–364, 1988.CrossRefGoogle Scholar
  34. 34.
    Affolter, V., P. Boujon, G. Bestetti, and G.L. Rossi, Hypothalamic and cortical neurons of normotensive and spontaneously hypertensive rats are differently affected by streptozotocin diabetes,Acta Neuropathol70: 135–141, 1986.PubMedCrossRefGoogle Scholar
  35. 35.
    Finegold, D., S.A. Lattimer, S. Nolle, M. Berstein, and DA. Green, Polyol pathway activity and myo-inositol metabolism. A suggested relationship in the pathogenesis of diabetic neuropathy,Diabetes32: 988–992, 1983.PubMedCrossRefGoogle Scholar
  36. 36.
    Cumming, D.C., M.E. Quigley, and S.S.C. Yen, Acute suppression of circulating testosterone levels by Cortisol in men, JClin Endocrinol Metab57: 671–673, 1983.PubMedCrossRefGoogle Scholar
  37. 37.
    Whitaker, M.D., B. Corenblum, P.J. Taylor, and P.H. Harasym, Control of the hypoglycemia release of prolactin, In M. L’Hermite and S.J. Judd (eds)Progress in Reproductive Biology: Advances in Prolactin,Volume 6, Karger, Basel, pp. 77–82, 1980.Google Scholar
  38. 38.
    Cryer, P.E., Glucose counterregulation in man,Diabetes30: 261–264, 1981.PubMedGoogle Scholar
  39. 39.
    Santeusanio, F., G. Bolli, M. Massi-Benedetti, P. Defeo, G. Angeletti, P. Compagnucci, G. Calabrese, and P. Brunetti, Counterregulatory hormones during moderate, insulin-induced, blood glucose decrements in man, JClin Endocrinol Metab52: 477–482, 1981.PubMedCrossRefGoogle Scholar
  40. 40.
    Sacca, L., R. Sherwin, R. Hendler, and P. Felig, Influence of continuous physiologic hyperinsulinemia on glucose kinetics and counterregulatory hormones in normal and diabetic man, /Clin Invest63: 849–857, 1979.CrossRefGoogle Scholar
  41. 41.
    Schwartz, N.S., W.E. Clutter, S.D. Shah, and P.E. Cryer, Glycemic thresholds for activation of glucose counterregulatory systems are higher than the threshold for symptoms, JClin Invest79: 777–781, 1987.PubMedCrossRefGoogle Scholar
  42. 42.
    Watabe, T., K. Tanaka, M. Kumagae, S. Itoh, F. Takeda, K. Morio, M. Hasegawa, T. Horiuchi, S. Miyabe, and N. Shimizu, Hormonal responses to insulin-induced hypoglycemia in man, JClin Endocrinol Metab65: 1187–1191, 1987.PubMedCrossRefGoogle Scholar
  43. 43.
    Keller-Wood, M.E., C.E. Wade, J. Shinsako, L.C. Keil, G.R. Van Loon, and M.F. Dallman, Insulin-induced hypoglycemia in conscious dogs: effect of maintaining carotid arterial glucose levels on the adrencorticotropin, epinephrine and vasopressin responses,Endocrinology112: 624–632, 1982.CrossRefGoogle Scholar
  44. 44.
    Karteszi, M., M.F. Dallman, G.B. Markara, and E. Stark, Regulation of the adenocortical response to insulin-induced hypoglycemia,Endocrinology111: 535–541, 1982.PubMedCrossRefGoogle Scholar
  45. 45.
    Mezey, E., T.D. Reisine, M.J. Brownstein, M. Palkovits, and J. Axelrod, β-adrenergic mechanism of insulin-induced adrenocorticotropin release from the anterior pituitary,Science226: 1085–1087, 1984.PubMedCrossRefGoogle Scholar
  46. 46.
    Ježová, D., R. Kvetanský, K. Kovács, Z. Opršalová, M. Vigaš, and G.B. Makara, Insulin-induced hypoglycemia activates the release of adrenocorticotropin predominantly via central and propranolol insensitive mechanisms,Endocrinology120: 409–415, 1987.PubMedCrossRefGoogle Scholar
  47. 47.
    Plotsky, P.M., T.O. Bruhn, and W. Vale, Hypophysiotropic regulation of adrenocorticotropin secretion in response to insulin-induced hypoglycemia,Endocrinology117: 323–329,1985.PubMedCrossRefGoogle Scholar
  48. 48.
    Guillaume, V., M. Grino, B. Conte-Devolx, F. Boudouresque, and C. Oliver, Corticotropin-releasing factor secretion increases in rat hypophysial portal blood during insulin-induced hypoglycemia,Neuroendocrinology49: 676–679, 1989.PubMedCrossRefGoogle Scholar
  49. 49.
    Caraty, A., M. Grino, A. Locatelli, and C. Oliver, Secretion of corticotropin releasing factor (CRF) and vasopressin (AVP) into hypophysial portal blood of conscious, unrestrained rams,Biochem Biophys Res Comm155: 841–849, 1988.PubMedCrossRefGoogle Scholar
  50. 50.
    Caraty, A., M. Grino, A. Locatelli, V. Guillaume, F. Boudouresque, B. Conte-Devolx, and C. Oliver, Effect of insulin-induced hypoglycemia on corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) secretion into hypophysial portal blood of conscious, unrestrained rams, JClin InvestSubmitted.Google Scholar
  51. 51.
    Oomura, Y., Glucose as a regulator of neuronal activity,Adv Metab Disorders10: 31–65, 1983.Google Scholar
  52. 52.
    Guillaume, V., B. Conte-Devolx, A. Szafarczyk, F. Malaval, N. Pares-Herbute, M. Grino, G. Alonso, I. Assenmacher, and C. Oliver, The corticotropin-releasing factor release in rat hypophysial portal blood is mediated by brain catecholamines,Neuroendocrinology46: 143–146, 1987.PubMedCrossRefGoogle Scholar
  53. 53.
    Szafarczyk, A., F. Malaval, A. Laurent, R. Gibaud, and I. Assenmacher, Further evidence for a central stimulatory action of catecholamines on adrenocorticotropin release in the rat,Endocrinology121: 883–892, 1987.PubMedCrossRefGoogle Scholar
  54. 54.
    Plotsky, P.M., Facilitation of immunoreactive corticotropin-releasing factor secretion into the hypophysial portal circulation after activation of catecholaminergic pathways or central norepinephrine injection,Endocrinology121: 924–930, 1987.PubMedCrossRefGoogle Scholar
  55. 55.
    Smythe, G.A, J.E. Bradshaw, M.V. Nicholson, H.S. Grunstein, and L.H. Storelien, Rapid bidirectional effects of insulin on hypothalamic noradrenergic and serotoninergic neuronal activity in the rat: role of glucose homeostasis,Endocrinology117: 1590–1597, 1985.PubMedCrossRefGoogle Scholar
  56. 56.
    Takahashi, K., W.H. Daughaday, and D.M. Kipnis, Regulation of immunoreactive growth hormone secretion in male rats,Endocrinology88: 909–917, 1971.PubMedCrossRefGoogle Scholar
  57. 57.
    Berelowitz, M., D. Dudlak, and LA. Frohman, Release of somatostatin-like immunoreactivity from incubated rat hypothalamus and cerebral cortex, JClin Invest69: 1293–1301, 1982.PubMedCrossRefGoogle Scholar
  58. 58.
    Berelowitz, M., N.C. Ting, and L. Murray, Glucopenia-mediated release of somatostatin from incubated rat hypothalamus: monosaccharide specificity and role of glycolytic intermediates,Endocrinology124: 826–830, 1989.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • M. Grino
    • 1
  • V. Guillaume
    • 1
  • A. Caraty
    • 1
    • 2
  • B. Conte-Devolx
    • 1
  • P. Joanny
    • 1
  • F. Boudouresque
    • 1
  • G. Pesce
    • 1
  • J. Steinberg
    • 1
  • G. Peyre
    • 1
  • A. Dutour
    • 1
  • P. Giraud
    • 1
  • C. Oliver
    • 1
  1. 1.Faculté de Médecine NordLaboratoire de Neuroendocrinologie Expérimentale, INSERM U 297Marseille Cédex 15France
  2. 2.Laboratoire de Neuroendocrinologie, Physiologie de la ReproductionINRANouzillyFrance

Personalised recommendations