Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Somatostatin release from dispersed hypothalamic cells: effects of diabetes


We examined the release of growth hormone-release inhibiting factor (somatostatin) from dispersed hypothalamic cells obtained from mature diabetic rodents and normal age-matched controls, in an attempt to demonstrate a possible hypothalamic defect which might underlie some of the reported abnormalities in somatotrophic function in diabetes mellitus. Insulinopoenic diabetes was induced by either streptozotocin or alloxan. Somatostatin release from cells from diabetic rats was diminished both basally and after stimulation by membrane depolarisation. Stimulated release was calcium dependent in cells from both normal and diabetic animals. The defect was present in both streptozotocin and alloxan induced diabetes. We also compared hypothalamic somatostatin release from cells obtained from obese hyperinsulinaemic C57 BL/Ks db/db diabetic mice and non diabetic lean litter mates (db/-). Despite longstanding marked hyperglycaemia, no significant alteration in somatostatin release was apparent. Likewise, starvation of rats for 5 days did not result in significant diminution of somatostatin release. These observations document a defect in hypothalamic somatostatin release in experimentally induced insulinopoenic diabetes, which is not apparent in the db/db mouse, suggesting that glucose per se is not responsible. Rather than the anticipated increase in hypothalamic somatostatin release in insulinopoenic diabetes, a reduction in release was observed. These observations are compatible with the hypothesis that increased hypothalamic somatostatin release is not responsible for abnormal growth hormone secretion in this model.


  1. 1.

    Williams RH, Porte D, Jr (1974) The pancreas. In: Williams RH (ed) Textbook of endocrinology. Saunders, Philadelphia, pp 502–626

  2. 2.

    Gerris DR, Smith C, Davis D, Diani AR and Gerritsen GC (1982) Morphometric evaluations of the hypothalamic-ovarian axis of the ketonuric, diabetic Chinese hamster: relationship to the reproductive cycle. Diabetologia 23: 275–279

  3. 3.

    Bray GA, York DA (1979) Hypothalamic and genetic obesity in experimental animals: an anatomic and endocrine hypothesis. Physiol Rev 59: 719–809

  4. 4.

    Hansen AP, Johansen K (1971) Diurnal serum growth hormone levels in poorly and well controlled juvenile diabetics. Diabetes 20: 239–245

  5. 5.

    Hansen AP (1970) Abnormal serum growth hormone response to exercise in juvenile diabetes. J Clin Invest 49: 1467–1478

  6. 6.

    Merimee TJ, Fitzgerald CR, Gold LA, McCourt JP (1979) Characteristics of growth hormone secretion in clinically stable diabetes. Diabetes 28: 308–312

  7. 7.

    Desjardins C (1969) Pituitary growth hormone and its hypothalamic releasing factor in normal and genetically diabetic mice. Proc Soc Exp Biol Med 130: 1–4

  8. 8.

    Deslex P, Rossi GL (1976) Quantitative evaluation of somatotrophic cells in the adenohypophysis of normal and diabetic male Chinese hamsters. Diabetologia 12: 489–493

  9. 9.

    Tannenbaum GS (1981) Growth hormone secretory dynamics in streptozotocin diabetes: evidence of a role for endogenous circulating somatostatin. Endocrinology 108: 76–82

  10. 10.

    Tannenbaum GS, Colle E, Gurd W, Wannamaker L (1981) Dynamic time-course studies of the spontaneously diabetic BB Wistar rat. Longitudinal profiles of plasma growth hormone, insulin and glucose. Endocrinology 100: 1872–1879

  11. 11.

    Patel YC, Cameron DP, Bankier A, Malaisse-Lagae F, Ravazzola M, Studer P, Orci L (1978) Changes in somatostatin concentration in pancreas and other tissues of streptozotocin diabetic rats. Endocrinology 103: 917–923

  12. 12.

    Dolais-Kitabgi J, LaMarschaud-Brustel Y, Freychet P (1979) Somatostatin in the pancreas and hypothalamus of obese mice. Diabetologia 17: 277–281

  13. 13.

    Makino H, Matsushima Y, Kanatsuka A, Yamamoto M, Kumagai A, Nishimura M (1979) Changes in pancreatic somatostatin constant in spontaneously diabetic mice, as determined by radioimmunoassay and immunohistochemical methods. Endocrinology 104: 243–247

  14. 14.

    Patel YC, Cameron DP, Stefan Y, Malaisse-Lagae F, Orci L (1977) Somatostatin: widespread abnormality in tissue of spontaneoulsy diabetic mice. Science 198: 930–931

  15. 15.

    Richardson SB, Greenleaf PW, Hollander CS (1983) Somatostatin release from dispersed hypothalamic cells. Effects of membrane depolarization, calcium and glucose deprivation. Brain Res 266: 75–81

  16. 16.

    Richardson SB, Nguyen T, Hollander CS (1983) Dopamine stimulates somatostatin release from perifused rat hypothalamus cells. Am J Physiol (E&M) 244: E560–566

  17. 17.

    Richardson SB, Twente S (1985) Mouse hypothalamic somatostatin release: roles of calcium and calmodulin. Endocrinology 117: 369–375

  18. 18.

    Richardson SB, Twente S (1986) Inhibition of rat hypothalamic somatostatin release by somatostatin: evidence for somatostatin ultrashort-loop feedback. Endocrinology 118: 2076–2082

  19. 19.

    Fischer LJ, Rickert DE (1975) Pancreatic islet cell toxicity. CRC Crit Rev Toxicol 231–263

  20. 20.

    Coleman DL (1978) Obese and diabetes: two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia 14: 141–148

  21. 21.

    Richardson SB, Hollander CS, DeLetto RD, Greenleaf PW, Thaw C (1980) Acetylcholine inhibits the release of somatostatin from rat hyothalamus in vitro. Endocrinology 107: 122–129

  22. 22.

    Berelowitz M, Dudlak D, Frohman LA (1982) Release of somatostatin-like immunoreactivity from incubated hypothalamus and cerebral cortex. Effects of glucose and glucoregulatory hormones. J Clin Invest 69: 1293–1301

  23. 23.

    Lengyel AM, Grossman A, Nieuwenhuyzen-Kruseman AC, Ackland J, Rees LH, Besser GM (1984) Glucose modulation of somatostatin and LHRH release from rat hypothalamic fragments in vitro. Neuroendocrinology 39: 31–38

  24. 24.

    Hollander CS, Richardson S, Ferdinand P, Greenleaf P (1979) Thyrotropin releasing factor secretion from dispersed rat hypothalamic cells is stimulated by potassium depolarization and glucose deprivation. Proceedings of the Annual Endocrine Society Meeting 426 (Abstract)

  25. 25.

    Molina JM, Premdas FH, Klenck RE, Eddlestone G, Oldham SB, Lipson LG (1984) The dynamic insulin secretory response of isolated pancreatic islets of the diabetic mouse. Diabetes 33: 1120–1123

  26. 26.

    Shapiro B, Berelowitz M, Pimstone BL, Kronheim S, Sheppard M (1979) Tissue and serum somatostatin-like immunoreactivity in fed, 15 h-fasted and 72 h fasted rats. Diabetes 28: 182–184

  27. 27.

    Tannenbaum GS, Rorstad O, Brazeau P (1979) Effects of prolonged food deprivation on the ultradian growth hormone rhythm and immunoreactive somatostatin tissue levels in the rat. Endocrinology 104: 1733–1738

  28. 28.

    Malthaei S, Horuk R, Olefsky JM (1986) Blood-brain glucose transfer in diabetes mellitus: decreased number of glucose transporters at blood-brain barrier. Diabetes 35: 1181–1184

  29. 29.

    Chu PCV, Lin MT, Shian LR, Len SY (1986) Alterations in physiological functions and in brain monoamine content in streptozotocin-diabetic rats. Diabetes 35: 481–485

  30. 30.

    Tesone M, Lodenheim RG, Cheb-Terrab R, Chiauzzi V, Solano A, Podesta E, Charreau EH (1986) Comparison between bioactive and immunoreactive luteinizing hormone (LH) in ovariectomized streptozotocin induced diabetic rats: response to LH-releasing hormone. Endocrinology 119: 2412–2416

  31. 31.

    Gibson MJ, DeNicola AF, Krieger DT (1985) Streptozotocin-induced diabetes is associated with reduced immunoreactive Betaendorphin concentrations in neurointermediate pituitary lobe and with disrupted circadian periodicity of plasma corticosterone levels. Neuroendocrinology 41: 64–71

  32. 32.

    Forman LJ, Marquis DE, Stevens R, Adler R, Vasilenko P (1985) Diabetes induced by streptozotocin results in a decrease in immunoreactive Beta endorphin levels in the pituitary and hypothalamus of female rats. Diabetes 34: 1104–1107

  33. 33.

    Palmer GG, Wilson GL, Chronister RB (1983) Streptozotocin-induced diabetes produces alterations in adenylate cyclase in rat cerebrum, cerebral microvessels and retina. Life Sci 32: 365–374

  34. 34.

    Lozovsky D, Saller CF, Kopin IJ (1981) Dopamine receptor binding is increased in diabetic rats. Science 214: 1031–1033

  35. 35.

    Schusdziarra V, Dobbs RE, Harris, Unger RH (1977) Immunoreactive somatostatin levels in plasma of normal and alloxan diabetic dogs. FEBS Lett 81: 69–72

  36. 36.

    Patel YC, Weir GG (1976) Increased somatostatin content of islets from streptozotocin diabetic rats. Clin Endocrinol (Oxf) 5: 191–194

  37. 37.

    Berelowitz M, Shapiro B, Pimstone B, Kronheim S (1979) Growth hormone release inhibitory hormone like immunoreactivity in pancreas and gut in streptozotocin diabetes and response to insulin administration. Clin Endocrinol (Oxf) 10: 195–198

  38. 38.

    Berelowitz M, Szabo M, Frohman LA, Firestone S, Chu L, Hintz RL (1981) Somatomedin-C mediates growth hormone negative feedback by effects on both the hypothalamus and pituitary. Science 212: 1279–1281

  39. 39.

    Sheppard MC, Kronheim S, Pimstone BL (1978) Stimulation by growth hormone of somatostatin release from the rat hypothalamus in vitro. Clin Endocrinol (Oxf) 9: 583–586

  40. 40.

    Phillips LS, Young HS (1976) Nutrition and somatomedin II. Serum somatomedin activity and cartilage growth activity in streptozotocin-diabetic rats. Diabetes 25: 516–527

  41. 41.

    Peterfreund RA, Vale WW (1984) Somatostatin analogs inhibit somatostatin secretion from cultured hypothalamus cells. Neuroendocrinol 39: 397–402

  42. 42.

    Lumpkin M, Negro-Vilar A, McCann SM (1981) Paradoxical elevation of growth hormone by intraventricular somatostatin: possible ultrashort-loop feedback. Science 211: 1072–1074

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Richardson, S.B., Twente, S. Somatostatin release from dispersed hypothalamic cells: effects of diabetes. Diabetologia 30, 893–898 (1987).

Download citation

Key words

  • Somatostatin
  • hypothalamus
  • diabetes
  • streptozotocin