Summary
Pancreatic glucagon responses to different amounts of intravenous arginine and glucose were studied in 10 insulin-dependent diabetics, 14 healthy controls (high insulin responders) and 15 subjects with decreased insulin response to glucose but normal intravenous glucose tolerance (low insulin responders). The dose-kinetics of the glucagon response was studied by using four different arginine doses. The suppressive effect of glucose was evaluated by infusing three glucose doses during a submaximal stimulation with arginine. The diabetics were tested first when under fair metabolic control and then following intensive treatment with insulin to produce near-normalisation of blood glucose. Finally, five subjects underwent insulin-induced hypoglycaemia. The changes in plasma glucagon and blood α-amino-nitrogen in response to the four arginine doses were significantly correlated in all groups but the slope of the dose response curve was steeper in the poorly controlled-diabetics than in the non-diabetics. These diabetics displayed higher fasting plasma glucagon values than healthy controls (high insulin responders) (224±4 versus 151±22 pg/ml, p<0.01), higher plasma glucagon responses to arginine and an absence of inhibition by glucose of the arginine-stimulated glucagon release. In strictly controlled diabetic patients, fasting plasma glucagon levels (176±16 pg/ml) were not significantly different from healthy controls, the glucagon response to arginine returned to the normal range, A cell suppressibility by glucose was restored and A cell stimulation by hypoglycaemia reappeared. In the low insulin responders, fasting plasma glucagon was not different from that of high responders (107±12 pg/ml), the slope of the dose response curve to arginine was similar in both groups and the A cells were inhibited by glucose to a similar extent. These results support the concept that islet A cell dysfunction in diabetes is not a primary phenomenon.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Unger RH (1976) Diabetes and the alpha cell. Diabetes 25: 136–151
Gerich JE, Lorenzi M, Karam JH, Schneider V, Forsham PH (1975) Abnormal pancreatic glucagon secretion and postprandial hyperglycaemia in diabetes mellitus. J Am Med Assoc 234: 159–165
Felig R, Wahren T, Sherwin R, Hendler R (1976) Insulin, glucagon and somatostatin in normal physiology and diabetes mellitus. Diabetes 25: 1901–1099
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
Gerich JE, Tsalikian E, Lorenzi M, Karam JH, Schneider V, Gustafson G, Bohannon NV (1975) Normalization of fasting hyperglucagonaemia and excessive glucagon responses to I. V. arginine in human diabetes mellitus by prolonged perfusion of insulin. J Clin Endocrinol Metab 41: 1178–1180
Raskin P, Unger RH (1978) Effects of insulin therapy on the profile of plasma immunoreactive glucagon in juvenile type and adult-type diabetics. Diabetes 27: 411–419
Raskin P, Unger RH (1978) Hyperglucagonaemia and its suppression. N Engl J Med 299: 433–436
Raskin R, Pietri A, Unger RH (1979) Changes in glucagon levels after 4 to 5 weeks of glucoregulation by portable insulin infusion pumps. Diabetes 28: 1033–1035
Cerasi E, Luft R (1967) The plasma insulin response to glucose infusion in healthy subjects and in diabetes mellitus. Acta Endocrinol 55: 278–304
Cerasi E, Luft R (1967) Follow-up of non-diabetic subjects with normal and decreased insulin response to glucose infusion. First report. Horm Metab Res (Suppl) 5: 111–120
Hugget ASG, Nixon DA (1957) Use of glucose oxidase, peroxi-dase, and O-dianisidine in determination of blood and urinary glucose. Lancet 2: 368–370
Malangeau P, Bourdon R, Nicaise AM, Masson B (1963) Dosage des acides aminés dans les liquides de l'organisme. Ann Biol Clin 21: 3–9
Williamson DH (1970) Alanine. In: Bergmeyer HU (ed) Methoden der enzymatischen Analyse. Verlag Chemie, Weinheim 1364–1373
Assan R, Tchobroutsky G, Derot M (1971) Glucagon radioimmunoassay, technical problems and recent data. Horm Metab Res (Suppl) 3: 82–90
Snedecor GW (1956) Statistical methods, 5th ed. Towa State College Press
Assan R, Hautecouverture M, Guillemant S, Dauchy F, Protin P, Derot M (1969) Evolution de paramètres hormonaux (glucagon, cortisol, hormone somatotrope) et énergétiques (glucose, acides gras libres, glycérol) dans 10 acidocétoses diabétiques graves traitées. Pathol Biol 17: 1095–1105
Assan R, Rosselin G, Drouet J, Dolais J, Tchobroutsky G (1966) Taux plasmatique du glucagon chez les diabétiques. Ann Endocrinol (Paris) 27: 6–12
Unger RH, Aguilar-Parada E, Müller WA, Eisentraut AM (1970) Studies of pancreatic alpha cell function in normal and diabetic subjects. J Clin Invest 49: 837–848
Müller WA, Faloona GR, Aguilar-Parada E, Unger RH (1970) Abnormal alpha cell function in diabetes: responses to carbohydrate and protein ingestion. N Engl J Med 283: 109–115
Gerich JE, Langlois M, Noacco C, Lorenzi M, Karam JH, Forsham PH (1976) Comparison of the suppressive effects of elevated plasma glucose and free fatty acid levels on glucagon secretion in normal and insulin-dependent diabetic subjects. J Clin Invest 58: 320–325
Ohneda A, Ishii S, Horigome K, Yamagata S (1975) Glucagon response to arginine after treatment of diabetes mellitus. Diabetes 24: 811–819
Unger RH, Madison LL, Müller WA (1972) Abnormal cell function in diabetes. Response to insulin. Diabetes 21: 301–307
Braaten JT, Faloona GR, Unger RH (1974) The effect of insulin on the alpha-cell response to hyperglycaemia in long-standing alloxan diabetes. J Clin Invest 53: 1017–1021
Raskin P, Aydin I, Unger RH (1976) Effect of insulin on the exaggerated glucagon response to arginine stimulation in diabetes mellitus. Diabetes 25: 227–229
Raskin P, Fujita Y, Unger RH (1975) Effect of insulin-glucose infusions on plasma glucagon levels in fasting diabetics and non-diabetics. J Clin Invest 56: 1132–1138
Gerich JE, Lorenzi M, Tsalikian E, Bohannon NV, Schneider V, Karam JH, Forsham PH (1976) Effects of acute insulin withdrawal and administration on plasma glucagon responses to intravenous arginine in insulin-dependent diabetic subjects. Diabetes 25: 955–960
Kerner W, Pfeiffer EF (1977) Glucagon secretion in diabetics during glucose-controlled insulin infusion. Diabetologia 13: 408
Unger RH, Madison LL, Müller WA (1972) Abnormal alpha-cell function in diabetics: response to insulin. Diabetes 21: 301–307
Unger RH, Raskin P, Srikant CG, Orci L (1977) Glucagon and the A-cell. Rec Prog Horm Res 33: 477
Aronoff SL, Bennett PH, Rushforth NB, Miller M, Unger RH (1976) Arginine-stimulated hyperglucagonaemia in diabetic Pima Indians. Diabetes 25: 404–407
Aronoff SL, Bennett PH, Unger RH (1977) Immunoreactive glucagon (IRG) response to intravenous glucose in pre-diabetes among Pima Indians and normal Caucasians. J Clin Endocrinol Metab 44: 968–972
Pagliara AS, Stillings SN, Raymond MW, Hover BA, Matschinsky FM (1975) Insulin and glucose as modulators of the amino-acid-induced glucagon release in the isolated pancreas of alloxan and streptozotocin diabetic rats. J Clin Invest 55: 244–255
Weir GC, Knowlton SD, Atkins RF, Mac Kennan KX, Martin DB (1976) Glucagon secretion from the perfused pancreas of streptozotocin-treated rats. Diabetes 25: 275–282
Bennett PH, Aronoff SL, Unger RH (1976) Evidence for an insulin-independent alpha-cell abnormality in human diabetes. Metabolism 25: 1527–1529
Turner RC, Harris E, Bloom SR, Wren C (1977) Relationship of fasting plasma glucose concentration to plasma insulin and glucagon concentrations.Studies in latent diabetics and women who have produced large-for-date babies. Diabetes 26: 166–171
Ganda OP, Soeldner JS, Gleason RE, Smith TM, Kilo C, Willanson JR (1977) Monozygotic triplets with discordance for diabetes mellitus and diabetic microangiopathy. Diabetes 26: 469–479
Day JL, Tattersall RB (1975) Glucagon secretion in unaffected monozygotic twins of juvenile diabetics. Metabolism 24: 145–151
Kirk RD, Dunn PJ, Reaven DW, Donald RA (1975) Abnormal pancreatic alpha-cell function in first-degree relatives of known diabetics. J Clin Endocrinol Metab 40: 913–916
Cerasi E, Wahren J, Luft R, Felig P, Hendler R (1973) The regulation of splanchnic glucose production in subjects with low insulin response. A compensatory mechanism in prediabetes? Eur J Clin Invest 3: 193–200
Cherrington A, Vranic M (1974) Effect of interaction between insulin and glucagon on glucose turnover and FFA concentration in normal and depancreatized dogs. Metabolism 23: 729–744
Sherwin R, Wahren J, Felig P (1976) Evanescent effects of hypo and hyperglucagonaemia on blood glucose homeostasis. Metabolism 25: 1381–1383
Bomboy JD, Lewis SB, Lacy WW, Sinclair-Smith BC, Liljenquist JE (1977) Transient stimulatory effect of sustained hyperglucagonaemia on splanchnic glucose production in normal and diabetic man. Diabetes 26: 1777–1784
Raskin P, Unger RH (1977) Effects of exogenous hyperglucagonaemia in insulin-treated diabetics. Diabetes 26: 1034–1039
Barnes AJ, Bloom SR, Mashiter K, Alberti KGMM, Smythe P, Turnell D (1977) Persistent metabolic abnormalities in diabetes in the absence of glucagon. Diabetologia 13: 71–75
Dobbs R, Sakurai H, Sazaki H, Faloona G, Valverde I, Baetens D, Orci L, Unger RH (1975) Glucagon: role in the hyperglycaemia of diabetes mellitus. Science 187: 544–547
Mc Garry JD, Foster DW (1977) Hormonal control of ketogenesis. Arch Intern Med 137: 495–501
Rizza RA, Gerich JE (1979) Persistent effect of sustained hyperglucagonaemia on glucose production in man. J Clin Endocrinol Metab 48: 352–355
Rizza R, Verdonk C, Miles J, Service FJ, Gerich JE (1979) Effect of intermittent endogenous hyperglucogonaemia on glucose homeostasis in normal and diabetic man. J Clin Invest 63: 1119–1123
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Assan, R., Efendic, S., Luft, R. et al. Dose-kinetics of pancreatic glucagon responses to arginine and glucose in subjects with normal and impaired pancreatic B cell function. Diabetologia 21, 452–459 (1981). https://doi.org/10.1007/BF00257785
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00257785