Summary
Fourteen insulin-treated diabetics were submitted to an arginine infusion test performed with either 11.7 or 5.85mg kg-1 min-1 arginine monohydrochloride infused during 40 min with or without previous oral administration of a low (75+50 mg) or a high (75 mg + 3 mg/kg) dose of indomethacin. Blood glucose, plasma non-esterified fatty acids, insulin, C-peptide and glucagon were determined at regular intervals before, during and after the arginine infusion. These parameters were totally unaffected by the two doses of indomethacin both in the basal state and during the arginine infusions at the two loads tested. Eight subjects had a basal C-peptide level above 0.07 pmol/ml and a mean (± SEM) maximal rise of 0.21±0.04 pmol/ml during the arginine infusion, whereas the remaining six patients had virtually zero values throughout the tests. The arginine-induced plasma glucagon rise was similar for the two rates of arginine infusion; the sum of the increments in plasma glucagon averaged 877±120 and 647±92 pg/ml (p>0.1) for the high and low rates of arginine infusion, respectively. The magnitude of the blood glucose rise appeared independent of the amount of arginine infused. Confirming previous reports, we found that the blood glucose rise after arginine was three to four times higher in subjects without C-peptide than in subjects with C-peptide. The mean glucagon response did not differ significantly between subjects with or without C-peptide. Thus, residual B cell function determines the magnitude of the blood glucose rise but not the glucagon response after intravenous arginine.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Bratusch-Marrain P, Björkman O, Hagenfeldt L, Waldhäusl W, Wahren J (1979) Influence of arginine on splanchnic glucose metabolism in man. Diabetes 28: 126–131
Chen M, Robertson RP (1978) Restoration of the acute insulin response by sodium salicylate. A glucose dose-related phenomenon. Diabetes 27: 750–756
Christiansen AaH (1973) Radioimmunoelectrophoresis in the determination of insulin binding to IgG. Methodological studies. Horm Metab Res 5: 147–154
Dole VP, Meinertz H (1960) Microdetermination of long chain fatty acids in plasma and tissues. J Biol Chem 235: 2395–2399
Ekstrand R, Alván G, L'e Orme M, Lewander R, Palmer L, Sarby B (1980) Double-bind dose-response study of indomethacin in rheumatoid arthritis. Eur J Clin Pharmacol 17: 437–442
Flores AGA, Sharp GWG (1972) Endogenous prostaglandins and osmotic water flow in the toad bladder. Am J Physiol 223: 1392–1397
Giugliano D, Luyckx AS, Lefèbvre PJ (1980) Effect of acetylsalicylic acid on blood glucose, plasma FFA, glycerol, 3-hydroxybutyrate, alanine, C-peptide, glucagon and growth hormone responses to arginine in insulin-dependent diabetics. Diab Metab (Paris) 6: 39–46
Giugliano D, Torella R, Sgambato S, D'onofrio F (1978) Prostaglandin E1 increases basal glucagon in man. Pharmacol Res Commun 10: 813–821
Gonen B, Goldman J, Baldwin D, Goldberg RB, Ryan WG, Blix PM, Schanzlin D, Fritz KJ, Rubenstein AH (1979) Metabolic control in diabetic patients. Effect of insulin secretory reserve (measured by plasma C-peptide levels) and circulating insulin antibodies. Diabetes 28: 749–753
Hales CN, Randle PJ (1963) Immunoassay of insulin with insulin-antibody precipitate. Biochem J 88: 137–146
Heding LG (1975) Radioimmunological determination of human C-peptide in serum. Diabetologia 11: 541–548
Hendriksen C, Faber OK, Drejer J, Binder C (1977) Prevalence of residual beta cell function in insulin treated diabetics evaluated on the C-peptide response to intravenous glucagon. Diabetologia 13: 615–629
Lefèbvre PJ, Luyckx AS (1978) Stimulation of gastric-glucagon release by prostaglandin E1. Prostaglandins Med 1: 419–420
Lefèbvre PJ, Luyckx AS (1979) Glucagon and diabetes: A reappraisal. Diabetologia 16: 347–354
Lefèbvre PJ, Luyckx AS (1979) Glucagon. In: Gray CH, James VHT (eds) Hormones in blood, 3rd edn Academic Press, London, pp 171–223
Luyckx AS (1972) Immunoassays for glucagon. In: Lefèbvre PJ, Unger RH (eds) Glucagon: Molecular physiology. Clinical and Therapeutic implications. Pergamon Press, Oxford, p 285–298
Luyckx AS, Deliège M, Jardon-Jeghers CI, Lefèbvre PJ (1981) Insulin, prostaglandin E2 and glucagon release by human insuloma tissue incubated in vitro, influence of indomethacin. Diab Metab (Paris) 7: 13–17
Luyckx AS, Lefèbvre PJ (1978) Possible role of endogenous prostaglandins in glucagon secretion by isolated guinea-pig islets. Diabetologia 15: 411–416
Luyckx AS, Lefèbvre PJ (1979) Further studies on the role of prostaglandins in glucagon secretion. In: Abstracts of the Fourth International Prostaglandin Conference, Washington DC, 27–31 May p 72
Luyckx AS, Lefèbvre PJ (1980) Further studies on the role of prostaglandins in glucagon secretion. In: Andreani D, Lefèbvre PJ, Marks V (eds) Current views on hypoglycemia and glucagon. Proc of the Serono Symposia, vol 30. Academic Press, London, pp 47–56
Luyckx AS, Lefèbvre PJ (1980) Endogenous prostaglandins modulate glucagon secretion by isolated guinea-pig islets. In: Samuelsson B, Ramwell P, Paoletti R (eds) Advances in prostaglandin and thromboxane research, vol 8. Raven Press, New York, pp 1299–1302
McRae JR, Chen M, Robertson RP (1979) Improvement of defective insulin responses to glucose, arginine and adrenergic stimulation in diabetics by sodium salicylate. In: Abstracts of the Fourth International Prostaglandin Conference, Washington DC, 27–31 May, pp 79
Micossi P, Montiroli A, Baron SH, Tamayo RC, Mengel F, Bevilacqua M, Raggi U, Rorbiato G, Foa PP (1978) Aspirin stimulates insulin and glucagon secretion and increases glucose tolerance in normal and diabetic subjects. Diabetes 27: 1196–1204
Pace-Asciak C, Cole S (1975) Inhibitors of prostaglandin catabolism. I. Differential sensitivity of 9-PGDH, 13-PGR and 15-PGDH to low concentrations of indomethacin. Experientia 31: 143–147
Pek S, Tai TY, Elster E (1978) Stimulatory effects of prostaglandins E1, E2 and F2-alpha on glucagon and insulin release in vitro. Diabetes 27: 801–809
Robertson PR, Chen M (1977) A role for prostaglandin E in defective insulin secretion and carbohydrate intolerance in diabetes mellitus. J Clin Invest 60: 747–753
Sacca L, Perez G (1976) Influence of prostaglandins on plasma glucagon levels in the rat. Metabolism 25: 127–130
Shima K, Tanaka R, Morishita S, Tarui S, Kumahara Y, Nishikawa M (1977) Studies on the etiology of “Brittle diabetes”. Relationship between diabetic instability and insulinogenic reserve. Diabetes 26: 717–725
Soldin SJ, Gero T (1979) A liquid chromatography analysis for indomethacin in serum. Clin Chem 25: 589–591
Torella R, Giugliano D, Siniscalchio N, Sgambato S, D'Onofrio F (1979) Influence of acetylsalicylic acid on plasma glucose, insulin, glucagon and growth hormone levels following tolbutamide stimulation in man. Metabolism 28: 887–889
Torella R, Siniscalchio N, Improta L (1979) The influence of acetylsalicylic acid on insulin, glucagon and growth hormone plasma levels following glucose and arginine in man. Il Farmaco 34: 131–137
Vane JR (1971) Inhibition of prostaglandin synthesis as a mechanism of action of aspirin-like drugs. Nature New Biol 231: 232–235
Vierhapper H, Bratusch-Marrain P, Waldhaüsl W (1980) Unchanged arginine-induced stimulation of insulin, glucagon, growth hormone and prolactin after pretreatment with indomethacin in normal man. J Clin Endocrinol Metab 50: 1131–1134
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Luyckx, A.S., Mendoza, E. & Lefebvre, P.J. Failure of indomethacin to affect arginine-induced C-peptide and glucagon release in insulin-treated diabetics. Diabetologia 21, 376–382 (1981). https://doi.org/10.1007/BF00252685
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00252685