Summary
Glucose counter-regulation during insulin-induced hypoglycaemia was studied in Type 1 diabetic patients without evidence of autonomic neuropathy and compared with that of a non-diabetic control group. The glucose recovery rate following hypoglycaemia was delayed in the diabetic compared with the control subjects and this was most pronounced for the initial, rapid phase of glucose increase (glucose increase in 15 min, control: 1.1±0.1 versus 0.4±0.1 mmol/l; p<0.01). The release of glucagon during hypoglycaemia was blunted in the diabetic patients (maximal plasma levels, control: 148±25 versus 70±10pg/ml; p< 0.01). The adrenaline levels were also lower compared with the control subjects (maximal plasma levels, control: 7.23±1.21 versus 3.27±0.87 nmol/l; p<0.05). To evaluate the importance of the blunted glucagon response for the delayed glucose compensation, glucagon was infused during the hypoglycaemia. Overall glucose recovery rate was improved but did not return to normal. Consequently impaired glucagon release in the diabetic patients cannot alone explain impaired glucoregulation; the lower adrenaline levels and/or an effect of the previous glucose levels per se on hepatic glucose production are probably also of importance.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Lager I, Blohmé G, Smith U (1979) Effect of cardioselective and non-selective β-blockade on the hypoglycaemic response in insulin-dependent diabetics. Lancet 1: 458–462
Viberti GC, Keen H, Bloom SR (1980) Beta blockade and diabetes mellitus: Effect of oxprenolol and metoprolol on the metabolic, cardiovascular, and hormonal response to insulin-induced hypoglycaemia in insulin-dependent diabetics. Metabolism 29: 873–879
Bolli G, Calabrese G, DeFeo P, Compagnucci P, Zega G, Angeletti G, Cartechini MG, Santeusanio F, Brunetti P (1982) Lack of glucagon response in glucose counter-regulation in Type I (insulindependent) diabetics: absence of recovery after prolonged optimal insulin therapy. Diabetologia 22: 100–105
Hilsted J, Madsbad S, Krarup T, Sestoft L, Christenson NJ, Tronier B, Galbo H (1981) Hormonal, metabolic, and cardiovascular responses to hypoglycemia in diabetic autonomic neuropathy. Diabetes 30: 626–633
Lager I, Blohmé G, von Schenck H, Smith U (1982) Importance of glucose control for the recovery from hypoglycemia in insulin-dependent diabetics. Diabetes 31: 771–775
Rizza RA, Cryer PE, Gerich JE (1979) Role of glucagon, catecholamines, and growth hormone in human glucose counterregulation. J Clin Invest 64: 62–71
Garber AJ, Cryer PE, Santiago JV, Haymond MW, Pagliara AS, Kipnis DM (1976) The role of adrenergic mechanisms in the substrate and hormonal response to insulin-induced hypoglycaemia in man. J Clin Invest 58: 7–17
Gerich J, Cryer P, Rizza R (1980) Hormonal mechanisms in acute glucose counterregulation: the relative roles of glucagon, epinephrine, norepinephrine, growth hormone, and cortisol. Metabolism 29: 1164–1175
Feldman JM, Plonk JW, Bivens CH (1975) The role of cortisol and growth hormone in the counter-regulation of insulin-induced hypoglycaemia. Horm Metabol Res 7: 378–381
Lager I, Jagenburg R, von Schenk H, Smith U (1980) Effect of beta-blockade on hormone release during hypoglycaemia in insulindependent diabetics. Acta Endocrinol (Copenh) 95: 364–371
Gerich JE, Langlois M, Noacco C, Karam JH, Forsham PH (1973) Lack of glucagon response to hypoglycaemia in diabetes: evidence for an intrinsic pancreatic alpha cell defect. Science 182: 171–173
Benson JW, Johnson DG, Palmer J, Werner PL, Ensinck JW (1977) Glucagon and catecholamine secretion during hypoglycaemia in normal and diabetic man. J Clin Endocrinol Metab 44: 459–464
Campbell LW, Kraegen EW, Lazarus L (1977) Defective blood glucose counterregulation in diabetics is a selective form of autonomic neuropathy. Br Med J 2: 1527–1529
Santiago JV, Clarke WL, Shah SD, Cryer PE (1980) Epinephrine, norepinephrine, glucagon, and growth hormone release in association with physiological decrements in the plasma glucose concentration in normal and diabetic man. J Clin Endocrinol Metab 51: 877–883
Popp DA, Shah SD, Cryer PE (1982) Role of epinephrine-mediated β-adrenergic mechanisms in hypoglycaemic glucose counterregulation and posthypoglycemic hyperglycaemia in insulin-dependent diabetes mellitus. J Clin Invest 69: 315–326
Ewing DJ, Campbell I, Murray A, Nielson JMM, Clarke BF (1978) Immediate heart-rate response to standing: simple test for autonomic neuropathy in diabetes. Br Med J 1: 145–147
Mackay JD, Page M McB, Cambridge J, Watkins PJ (1980) Diabetic autonomic neuropathy. The diagnostic value of heart monitoring. Diabetologia 18: 471–478
Kuzuya H, Blix PM, Horwitz DL, Steiner DF, Rubenstein AH (1979) Determination of free and total insulin and C-peptide in insulin-treated diabetics. Diabetes 26: 22–29
von Schenck H (1977) Production and characterization of an antiserum against pancreatic glucagon. Clin Chim Acta 80: 455–463
von Schenck H, Nilsson O (1981) Radioimmunoassay of extracted glucagon compared with three non-extraction assays. Clin Chim Acta 109:183–191
Engelman K, Portnoy B (1970) A sensitive double-isotope derivate assay for norepinephrine and epinephrine. Circ Res 26: 53–55
Polonsky K, Bergenstal R, Pons G, Schneider M, Jaspan J, Rubenstein A (1982) Relation of counterregulatory responses to hypoglycaemia in Type I diabetics. N Engl J Med 307: 1105–1112
Hilsted J, Madsbad S, Krarup T, Heding LG, Sestoft L (1980) Metabolic responses to hypoglycemia in juvenile diabetics. Acta Med Scand 639: 25–28
Madsbad S, Hilsted J, Krarup R, Sestoft L, Christensen NJ, Faber OK, Tronier B (1982) Hormonal, metabolic and cardiovascular responses to hypoglycaemia in Type I (insulin-dependent) diabetes with and without residual B cell function. Diabetologia 23: 499–503
Bolli G, De Feo P, Compagnucci P, Cartechini MG, Angeletti G, Santeusanio F, Brunetti P, Gerich J (1983) Abnormal glucose counterregulation in insulin-dependent diabetes mellitus. Diabetes 32: 134–141
Palmer JP, Henry DP, Benson JW, Johnson DG, Ensinck JW (1976) Glucagon response to hypoglycaemia in sympathectomized man. J Clin Invest 57: 522–525
Walter RM, Dudl RJ, Palmer JP, Ensinck JW (1974) The effect of adrenergic blockade on the glucagon responses to starvation and hypoglycaemia in man. J Clin Invest 54:1214–1220
Ensinck JW, Walter RM, Palmer JP, Brodowns RG, Campbell RG (1976) Glucagon responses to hypoglycaemia in adrenalectomized man. Metabolism 25: 227–232
Palmer JP, Werner PL, Hollander P, Ensinck JW (1979) Evaluation of the control of glucagon secretion by the parasympathetic nervous system in man. Metabolism 28: 549–552
Corrall RM, Frier BM (1979) Acute hypoglycaemia in man: neural control of pancreatic islet cell function. Metabolism 30: 160–164
Patel DG (1983) Lack of glucagon response to hypoglycaemia in long-term experimental diabetic rats. Diabetes 32: 55–60
Hoeldtke R, Boden G, Shuman C, Owen O (1982) Reduced epinephrine secretion and hypoglycaemic unawareness in diabetic autonomic neuropathy. Ann Intern Med 96: 459–462
Otsuka K, Assaykeen TA, Goldfien A, Ganong WF (1970) Effect of hypoglycaemia on plasma renin activity in dogs. Endocrinology 87: 1306–1317
Blackard WG, Nelson NC, Andrews SS (1972) Portal and peripheral vein immunoreactive glucagon concentrations after arginine or glucose infusion. Diabetes 23: 199–202
Dencker H, Hedner P, Holst J, Tranberg K-G (1975) Pancreatic glucagon response to an ordinary meal. Scand J Gastroenterol 10: 471–474
Sacca L, Perez G, Carteni G, Rengo F (1977) Evaluation of the role of the sympathetic nervous system in the glucoregulatory response to insulin-induced hypoglycaemia in the rat. Endocrinology 101: 1016–1022
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lager, I., von Schenck, H. & Smith, U. Improved but not normalized glucose counter-regulation during glucagon infusion in Type 1 (insulin-dependent) diabetes. Diabetologia 26, 337–342 (1984). https://doi.org/10.1007/BF00266033
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00266033