Skip to main content
SpringerLink
Log in

Untersuchungen zur Glukagon-, STH- und Cortisolsekretion bei insulininduzierter Hypoglykämie bei insulinabhängigen Diabetikern (JDD) ohne autonome Neuropathie

Glucagon, growth hormone, and cortisol response to insulin-induced hypoglycemia in insulin-dependent diabetics (IDD) without autonomic neuropathy

  • Originalien
  • Published:
Klinische Wochenschrift Aims and scope Submit manuscript

Summary

Insulin-induced hypoglycemias are a sign of non-sufficient counterregulation, in which different contra-insulinary hormones participate. The aim of the study was to investigate, whether there exists a difference between IDD and non-diabetics regarding secretion of glucagon, cortisol, and growth hormone during an insulin-induced hypoglycemia and further on pointing out, expecially, the importance of glucagon.

Insulin-induced hypoglycemias are counterregulated in non-diabetics, not in IDD. The missing glucagon secretion during insulin-induced hypoglycemia in IDD seems to be independent from an autonomic neuropathy. Only after high doses of exogenous glucagon can one see a counterregulating increase of glucose.

The STH secretion is similar in non-diabetics and IDD during an insulin-induced hypoglycemia and has evidently only a secondary effect in hypoglycemic counterregulation. The STH secretion may be the expression of a diencephal-triggered stress situation.

The cortisol secretion is the same in both groups. The gluconeogenetic effect of cortisol is not sufficient to accomplish a fast compensation of hypoglycemia. This does not exclude long-term effects.

When inhibiting the secretion of insulin and different contra-insulinary hormones with somatostatin, one is able to demonstrate that glucagon alone is a sufficiently counterregulatory hormone in insulin-induced hypoglycemias.

Zusammenfassung

Insulininduzierte Hypoglykämien bei Diabetes mellitus sind Ausdruck unzureichender Gegenregulation, an der verschiedene kontrainsulinäre Hormone beteiligt sind. Ziel der vorgelegten Studie war es zu untersuchen, ob zwischen insulinabhängigen Diabetikern und Stoffwechselgesunden Unterschiede im Sekretionsverhalten von Glukagon, Cortisol und STH während einer insulininduzierten Hypoglykämie bestehen, und welche Bedeutung insbesondere Glukagon bei der Regulation insulininduzierter Hypoglykämien zukommt.

Insulininduzierte Hypoglykämien werden nur bei Stoffwechselgesunden und nicht aber bei insulinabhängigen Diabetikern durch endogenes Glukagon gegenregulatorisch beeinflußt. Während einer insulininduzierten Hypoglykämie bei insulinabhängigen Diabetikern ist die fehlende Glukagonsekretion während einer insulininduzierten Hypoglykämie nicht an das Vorliegen einer autonomen diabetischen Neuropathie gebunden, sondern scheint davon unabhängig zu sein. Bei insulinabhängigen Diabetikern wird ein gegenregulatorischer Glukoseanstieg erst nach Zufuhr relativ hoher Dosen exogenen Glukagons erreicht.

Die STH-Sekretion verhält sich während einer insulininduzierten Hypoglykämie bei Stoffwechselgesunden und insulinabhängigen Diabetikern ähnlich und hat offenbar für eine schnelle Hypoglykämiegegenregulation, wenn überhaupt, nur eine untergeordnete Bedeutung. Sie könnte vielmehr Ausdruck einer dienzephal ausgelösten Streßsituation sein.

Die Cortisolsekretion verhält sich wie die STH-Sekretion in beiden Kollektiven gleich. Der glukoneogenetische Effekt von Cortisol reicht nicht aus, um eine schnelle Hypoglykämiekompensation zu erzielen. Dies schließt langfristige Effekte nicht aus.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Literatur

  1. Bennett T, Farquhar IK, Hosking DJ, Hampton JR (1978) Assessment of methods for estimating autonomic nervous control of the heart in patients with diabetes mellitus. Diabetes 27:1167

    PubMed  Google Scholar 

  2. Benson JW, Johnson DG, Palmer JP, Werner PL, Ensinck JW (1977) Glucagon and catecholamine secretion during hypoglycemia in normal and diabetic man. J Clin Endocrinol Metab 44:459

    PubMed  Google Scholar 

  3. Bloom SR, Vaughan NJA, Russell RCG (1974) Vagal control of glucagon release in man. Lancet 2:546

    PubMed  Google Scholar 

  4. Cahill GF jr (1971) Action of adrenal cortical steroids on carbohydrate metabolism. In: Christy NP (ed) The human adrenal cortex. Harper and Row, New York, pp 205–239

    Google Scholar 

  5. Campbell IW, Ewing DJ, Clarke BF (1980) Tests of cardiovascular reflex function in diabetic autonomic neuropathy. Workshop on diabetic encephalopathy and neuropathy, Düsseldorf, May 3–4, 1978. In: Hormone and metabolic research (Suppl). Thieme, Stuttgart (in press)

    Google Scholar 

  6. Cicmir I, Gries FA (1980) Studies of heart rate oscillations at rest in diabetes mellitus. Workshop on diabetic encephalopathy and neuropathy, Düsseldorf May 3–4, 1978. In: Hormone and metabolic research (Suppl). Thieme, Stuttgart (in press)

    Google Scholar 

  7. Cerasi E, Luft R (1970) Diabetes mellitus — a disorder of cellular information transmission? Horm Metab Res 2:246

    PubMed  Google Scholar 

  8. Christensen NJ (1974) Plasma norepinephrine and epinephrine in untreated diabetics, during fasting and after insulin administration. Diabetes 23:1

    PubMed  Google Scholar 

  9. Cryer PE (1976) Isotope-derivate measurements of plasma nore-pinephrine and epinephrine in man. Diabetes 25:1071

    PubMed  Google Scholar 

  10. Cryer PE, Silverberg AB, Santiago JV, Shah SD (1978) Plasma catecholamines in diabetes: The syndromes of hypoadrenergic and hyperadrenergic postural hypotension. Am J Med 64:407

    PubMed  Google Scholar 

  11. Defronzo RA, Andres R, Bledsoe TA, Boden GA, Faloona GA, Tobin JD (1977) A test of the hypothesis that the rate of fall in glucose concentration triggers counterregulatory hormonal responses in man. Diabetes 26:445

    PubMed  Google Scholar 

  12. Donald RA (1971) Plasma immunoreactive corticotrophin and cortisol response to insulin hypoglycemia in normal subjects and patients with pituitary disease. J Clin Endocrinol 32:225

    Google Scholar 

  13. Drost H (1978) Untersuchungen zur Glukagonsekretion und ihre metabolische Bedeutung bei Erkrankungen des Kohlenhydrat-und Fettstoffwechsels. Habilitationsschrift Düsseldorf

  14. Ensinck JW, Walter RM, Palmer JP, Brodows RG, Campbell RG (1976) Glucagon responses to hypoglycemia in adrenalectomized man. Metabolism 25:227

    PubMed  Google Scholar 

  15. Fatourechi V, Molnar D, Service FJ, Ackerman E, Rosevear JW, Moxness KE, Taylor WF (1969) Growth hormone and glucose interrelationships in diabetes: studies with insulin infusion during continuous blood glucose analysis. J Clin Endocrinol 29:319

    Google Scholar 

  16. Gerich JE, Karam JH, Forsham PH (1973) Stimulation of glucagon secretion by epinephrine in man. J Clin Endocrinol Metab 37:479

    PubMed  Google Scholar 

  17. Gerich JE, Langlois M, Noacco C, Karam JH, Forsham PH (1973) Lack of glucagon response to hypoglycemia in diabetes: Evidence for an intrinsic pancreatic alpha cell defect. Science 182:171

    PubMed  Google Scholar 

  18. Gerich JE, Schneider V, Dippe SE, Langlois M, Noacco C, Karam JH, Forsham PH (1974) Characterization of the glucagon response to hypoglycemia in man. J Clin Endocrinol Metab 38:77

    PubMed  Google Scholar 

  19. Gerich JE, Lorenzi M, Karam JH, Schneider V, Forsham PH (1975) Abnormal pancreatic glucagon secretion and postprandial hyperglycemia in diabetes mellitus. JAMA 234:159

    PubMed  Google Scholar 

  20. Gerich JE, Lorenzi M, Tsalikian E, Karam JH (1976) Studies on the mechanism of epinephrine-induced hyperglycemia in man. Diabetes 25:65

    PubMed  Google Scholar 

  21. Gerich JE, Davis J, Lorenzi M, Bohannon N, Cryer P (1977) Interaction of catecholamines and glucagon in glucose counter-regulation. Diabetes 26:[Suppl 1] 384

    Google Scholar 

  22. Glick SM (1970) Hypoglycemic threshold for human growth hormone release. J Clin Endocrinnol 30:619

    Google Scholar 

  23. Grady HJ, Lamar MA (1959) Glucose determination by automatic chemical analysis. Clin Chem 5:542

    PubMed  Google Scholar 

  24. Greenwood FC, Landon J, Stamp TCB (1966) The plasma sugar, free fatty acid, cortisol and growth hormone response to insulin. I. In control subjects. J Clin Invest 45:429

    PubMed  Google Scholar 

  25. Gundersen HJG, Neubauer B (1977) A long-term diabetic autonomic nervous abnormality: Reduced variations in resting heart rate measured by a simple an sensitive method. Diabetologia 13:137

    PubMed  Google Scholar 

  26. Harries M, Prout BJ (1970) Relative hypoglycemia. Lancet 2:317

    Google Scholar 

  27. Heding LG, Rasmussen SM (1972) Determination of pancreatic and gut-glucagon immunoreactivity (GLI) in normal and diabetic subjects. Diabetologia 8:408

    PubMed  Google Scholar 

  28. Howell SL, Edwards JC, Montague W (1974) Regulation of adenylate cyclase and cyclic dependent protein kinase activities in A2-cell rich guinea pig islets of Langerhans. Horm Metab Res 6:49

    PubMed  Google Scholar 

  29. Jahnke K, Miß HD, Drost H (1974) Kriterien und Bewertung der Diabeteseinstellung. Dtsch Med Wochenschr 17:870

    Google Scholar 

  30. Kley HK, Krüskemper HL (1971) Bestimmung von 11-Hydroxy-und 11-Desoxycorticoiden aus der gleichen Plasmaprobe als Basis eines Metopironkurztestes. Z Klin Chem Klin Biochem 9:520

    PubMed  Google Scholar 

  31. Koh CS, Kohn J, Catt KJ, Burger HG (1968) Lack of relation between plasma-growth-hormone levels and small decrements in blood-sugar. Lancet 1:13

    PubMed  Google Scholar 

  32. Leclercq-Meyer V, Marchand J, Malaisse WJ (1976) The role of calcium in glucagon release, interactions between glucose and calcium. Diabetologia 12:531

    PubMed  Google Scholar 

  33. Lloyd-Mostyn RH, Watkins PJ (1975) Defective innervation of heart in diabetic autonomic neuropathy. Br Med J 3:15

    PubMed  Google Scholar 

  34. Lorenzi E, Tsalikian E, Karam JH, Gustafson G, Forsham PH (1975) Differential glucagon responses tol-Dopa, epinephrine and insulin-induced hypoglycemia in normal and insulin-dependent diabetic subjects. Diabetes 24:[Suppl 1] 411

    Google Scholar 

  35. Luft R, Cerasi E (1968) Human growth hormone as a regulator of blood glucose concentration and as a diabetogenic substance. Diabetologia 4:1

    PubMed  Google Scholar 

  36. Maher TD, Tanenberg RJ, Greenberg BZ, Hoffmann J, Doe RP, Goetz FC (1977) Lack of glucagon response to hypoglycemia in diabetic autonomic neuropathy Diabetes 26:196

  37. Marco J, Calle C, Roman D, Diaz-Fierros M, Villanueva ML, Valverde I (1973) Hyperglucagonism induced by glucocorticoid treatment in man. N Engl J Med 288:128

    PubMed  Google Scholar 

  38. Müller WA, Faloona GR, Aguilar-Parada E, Unger RH (1970) Abnormal alpha-cells function in diabetes N Engl J Med 283:109

    PubMed  Google Scholar 

  39. Murray A, Ewing DJ, Campbell IW, Neilson JMM, Clarke BF (1975) RR interval variations in young male diabetics. Br Heart J 37:882

    PubMed  Google Scholar 

  40. Nakagawa K, Horiuchi Y, Mashimo K (1971) Further studies on the relation between growth hormone and corticotropin secretion in insulin-induced hypoglycemia. J Clin Endocrinol 32:183

    Google Scholar 

  41. Ohneda A, Parada E, Eisentraut AM, Unger RH (1968) Characterization of response of circulating glucagon to intraduodenal and intravenous administration of amino acids. J Clin Invest 47:2305

    PubMed  Google Scholar 

  42. Palmer JP, Henry DP, Benson JW, Johnson DG, Ensinck JW (1976) Glucagon response to hypoglycemia in sympathectomized man. J Clin Invest 57:522

    PubMed  Google Scholar 

  43. Plonk JW, Bivens CH, Feldman JM (1974) Inhibition of hypoglycemia-induced cortisol secretion by the serotonin antagonist cyproheptadine. J Clin Endocrinol Metab 38:836

    PubMed  Google Scholar 

  44. Reynolds C, Molnar GD, Jiang NS, Jones JD, Taylor WF (1973) Abnormal glucagon response to hypoglycemia in unstable diabetics. Diabetes 22:[Suppl 1] 327

    Google Scholar 

  45. Roth J, Glick SM, Yalow RS, Berson SA (1964) The influence of blood glucose on the plasma concentration of growth hormone. Diabetes 13:355

    PubMed  Google Scholar 

  46. Sönksen PH, Tompkins CV, Srivastava MC, Nabarro JDN (1972) Growth hormone and cortisol responses to insulin infusion in patients with diabetes mellitus. Lancet 2:155

    PubMed  Google Scholar 

  47. Träger L (1977) Steroidhormone. Biosynthese, Stoffwechsel, Wirkung. Springer, Berlin Heidelberg New York, S 141–152

    Google Scholar 

  48. Unger RH, Aguilar-Parada E, Müller WA (1970) Studies of panceatic alpha-cells function in normal and diabetic subjects. J Clin Invest 49:837

    PubMed  Google Scholar 

  49. Unger RH, Lefebvre PJ (1972) Glucagon physiology. In: Lefebvre PJ, Unger RH (eds) Glucagon, molecular, physiology, clinical and therapeutic implications. Pergamon Press, Oxford, pp 213–244

    Google Scholar 

  50. Unger RH, Lefebvre PJ (1972) Glucagon, molecular physiology, clinical and therapeutic implications. Pergamon Press, Oxford

    Google Scholar 

  51. Walter RM, Dudl RJ, Palmer JP, Ensinck JW (1974) The effect of adrenergic blockade on the glucagon responses to starvation and hypoglycemia in man. J Clin Invest 54:1214

    PubMed  Google Scholar 

  52. Wheeler T, Watkins PJ (1973) Cardiac denervation in diabetes. Br Med J 4:584

    PubMed  Google Scholar 

  53. Wide L, Porath J (1966) Radioimmunoassay of proteins with the use of Sephadex-coupled antibodies. Biochim Biophys Acta (Amsterdam) 130:157

    Google Scholar 

  54. Wiegelmann W (1973) Wachstumshormon and Gonadotropine bei Erkrankungen des Hypothalamus-Hypophysen-Systems. Urban und Schwarzenberg, München Berlin Wien

    Google Scholar 

  55. Wiegelmann W, Kley HK, Solbach HG, Krüskemper HL (1974) Wachstumshormon, Gonadotropine und Cortisol im Plasma von Männern unter kombinierter Anwendung des Insulinhypoglykämie/LH-RH-Stimulationstestes. Klin Wochenschr 52:194

    PubMed  Google Scholar 

  56. Wise JK, Hendler R, Felig P (1973) Influence of glucocorticoids on glucagon secretion and plasma amino acid concentrations in man. J Clin Invest 52:277

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinische Abteilung des Diabetes-Forschungsinstitutes, Germany

    H. Drost, D. Grüneklee & F. A. Gries

  2. Medizinische Klinik und Poliklinik C, Universität Düsseldorf, Germany

    H. K. Kley, W. Wiegelmann & H. L. Krüskemper

Authors
  1. H. Drost
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Grüneklee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. K. Kley
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W. Wiegelmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. L. Krüskemper
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F. A. Gries
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Mit Unterstützung der Deutschen Forschungsgemeinschaft (SFB „113“ Diabetologie Düsseldorf)

Durch Inhibition der Sekretion von Insulin und verschiedener kontrainsulinärer Hormone mit Somatostatin kann gezeigt werden, daß Glukagon allein zur Gegenregulation der insulininduzierten Hypoglykämie ausreicht.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Drost, H., Grüneklee, D., Kley, H.K. et al. Untersuchungen zur Glukagon-, STH- und Cortisolsekretion bei insulininduzierter Hypoglykämie bei insulinabhängigen Diabetikern (JDD) ohne autonome Neuropathie. Klin Wochenschr 58, 1197–1205 (1980). https://doi.org/10.1007/BF01478876

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01478876

Key words

Schlüsselwörter

Search

Navigation