Summary
The present study aimed at investigating the hyperglycaemic, lipolytic and ketogenic effects of small doses of glucagon delivered continuously or in a pulsatile manner. The study was performed in eight healthy young volunteers (24.2±1.2 years) and in eight healthy aged subjects (69.4±2.0 years). In all the subjects, endogenous pancreatic hormone secretion was inhibited by somatostatin and only glucagon was replaced. Consequently, the effects of pulsatile and continuous glucagon delivery were studied in conditions of progressive somatostatin-induced insulin deficiency. In both the young and the aged subjects, pulsatile glucagon delivery resulted in increases in plasma glucose, non-esterified fatty acid, glycerol and β-hydroxybutyrate levels greater than those observed when the same amount of glucagon was delivered in a continuous manner. The net increases in plasma glucose, glycerol and non-esterified fatty acid levels were similar between the young and the aged subjects when glucagon was infused continuously; in contrast, the rise in plasma β-hydroxybutyrate in the aged was only about half that observed in the young subjects. Surprisingly, when glucagon was infused in a pulsatile manner, the rises in plasma glycerol, non-esterified fatty acid and β-hydroxybutyrate levels were all significantly smaller in the aged subjects, while no significant differences were observed in the blood glucose responses. We conclude that, in the presence of somatostatin-induced insulin deficiency, pulsatile glucagon exerts greater effects on blood glucose, plasma non-esterified fatty acid, glycerol and β-hydroxybutyrate levels than its continuous delivery. In the elderly, the lipolytic and ketogenic, but not the hyperglycaemic, responses to pulsatile glucagon are significantly reduced.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Goodner CJ, Walike BC, Koerker DJ, Ensinck JW, Brown AC, Chideckel E, Palmer JC, Kalnasy L (1977) Insulin, glucagon and glucose exhibit synchronous sustained oscillations in fasting monkeys. Science 195: 177–179
Lang DA, Matthews DR, Peto J, Turner RC (1979) Cyclic oscillations of basal plasma glucose and insulin concentrations in human beings. N Engl J Med 301: 1023–1027
Lefèbvre PJ, Paolisso G, Scheen AJ, Henquin JC (1987) Pulsatility of insulin and glucagon release: physiological significance and pharmacological implications. Diabetologia 30: 443–452
Matthews DR, Naylor BA, Jones RG, Ward GM, Turner RC (1983) Pulsatile insulin has greater hypoglycemic effect than continuous delivery. Diabetes 32: 617–621
Paolisso G, Sgambato S, Passariello N, Scheen AJ, D'Onofrio F, Lefèbvre PJ (1987) Greater efficacy of pulsatile insulin in type I diabetics critically depends on plasma glucagon levels. Diabetes 36: 566–570
Bratusch-Marrain PR, Komjati M, Waldhäusl WK (1986) Efficacy of pulsatile versus continuous insulin administration on hepatic glucose production and glucose utilization in type 1 diabetic humans. Diabetes 35: 922–926
Paolisso G, Scheen A, Lefèbvre PJ (1987) Greater inhibition of endogenous glucose production by pulsatile insulin delivery at basal glucagon levels in normal man. Diabetologia 30: 566A
Weigle DS, Koerker DJ, Goodner CJ (1984) Pulsatile glucagon delivery enhances production by perifused rat hepatocytes. Am J Physiol 247: E564-E568
Weigle DS, Goodner CJ (1986) Evidence that the physiological pulse frequency of glucagon secretion optimizes glucose production by perifused rat hepatocytes. Endocrinology 118: 1606–1613
Komjati M, Bratusch-Marrain P, Waldhäusl W (1986) Superior efficacy of pulsatile versus continuous hormone exposure on hepatic glucose production in vitro. Endocrinology 118: 312–319
Paolisso G, Scheen AJ, Luyckx AS, Lefèbvre PJ (1987) Pulsatile hyperglucagonemia fails to increase hepatic glucose production in normal man. Am J Physiol 252: E1-E7
Okuda Y, Kawai K, Yamashita K (1987) Age-related change in ketone body metabolism: diminished glucagon effect on ketogenesis in adult rats. Endocrinology 120: 2152–2157
Eggstein M, Kuhlmann E (1974) Triglycerides and glycerol; determination after alkaline hydrolysis. In: Bergmeyer HU (ed) Methods of enzymatic analysis, Vol 4. Verlag Chemie, Weinheim, and Academic Press Inc, New York, pp 1825–1831
Williamson DH, Mellanby J (1974) D-(-)-3 Hydroxybutyrate. In: Bergmeyer HU (ed) Methods of enzymatic analysis, Vol 4. Verlag Chemie Weinheim and Academic Press Inc, New York, pp 1836–1839
Dole VP, Meinertz H (1960) Microdetermination of long chain fatty acids in plasma and tissues. J Biol Chem 235: 2595–2599
Weigle DS (1987) Pulsatile secretion of fuel-regulatory hormones. Diabetes 36: 764–775
Unger RH, Lefèbvre PJ (1972) Glucagon physiology. In: Lefèbvre PJ, Unger RH (eds) Glucagon. Molecular physiology, clinical and therapeutic implications. Pergamon Press, Oxford, pp 213–244
Hansen BC, Jen K-LC, Koerker DJ, Goodner CJ, Wolfe RA (1982) Influence of nutritional state on periodicity in plasma insulin levels in monkeys. Am J Physiol 242: R255-R260
Jaspan JB, Lever E, Polonsky KS, Van Cauter E (1986) In vivo pulsatility of pancreatic islet peptides. Am J Physiol 251: E215-E226
Lefèbvre PJ (ed) (1983) Glucagon (Handbook of experimental pharmacology, vol 66 I and II). Springer, Berlin Heidelberg New York
Lefèbvre PJ (1983) Glucagon and adipose tissue lipolysis. In: Lefèbvre PJ (ed) Glucagon I. Handbook of experimental pharmacology, Vol 66. Springer, Berlin Heidelberg New York, pp 419–440
McGarry JD, Foster DW (1983) Glucagon and ketogenesis. In: Lefèbvre PJ (ed) Glucagon I. Handbook of experimental pharmacology, Vol 66. Springer, Berlin Heidelberg New York, pp 383–398
Holmm G, Jacobsson B, Björntorp P, Smith U (1975) Effect of age and cell size on rat adipose tissue metabolism. J Lipid Res 16: 461–464
Cooper B, Weinblatt F, Gregerman RI (1977) Enhanced activity of hormone-sensitive adenylate cyclase during dietary restriction in the rat: dependance on age and relation to cell size. J Clin Invest 59: 467–474
Bertrand HA, Masoro EJ, Byung PYU (1980) Maintenance of glucagon-promoted lipolysis in adipocytes by food restriction. Endocrinology 107: 591–595
Corvera S, Huerta-Bahena J, Pelton JT, Hruby VJ, Trivedi D, Garcia-Sainz JA (1984) Metabolic effects and cyclic AMP produced by glucagon, (1-N-triitrophenylhistidine, 12-homoarginine) glucagon, and forskolin in isolated rat hepatocytes. Bioch Bioph Acta 804: 434
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Paolisso, G., Buonocore, S., Gentile, S. et al. Pulsatile glucagon has greater hyperglycaemic, lipolytic and ketogenic effects than continuous hormone delivery in man: effect of age. Diabetologia 33, 272–277 (1990). https://doi.org/10.1007/BF00403320
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00403320