Skip to main content
SpringerLink
Log in

Glucagon and the Control of Appetite

  • Chapter
Glucagon III

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 123))

Abstract

Recent progress in behavioral neuroscience indicates that peripheral neural and endocrine feedback signals are crucial controls for the initiation, maintenance, and termination of meals, and, therefore, for total food intake and the maintenance of body weight (Campfield and Smith 1990; Scharrer and Langhans 1988; Smith and Gibbs 1992; Blundell 1991). I review here evidence that glucagon is one such signal. Results from tests of administration of glucagon or glucagon antagonists suggest that, under many conditions, glucagon released from the pancreas during meals acts in the liver to initiate a neural signal that is conveyed by vagal afferents to the brain, where it contributes to the termination of the meal.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Berthoud H-R, Jeanrenaud B (1982) Sham feeding-induced cephalic phase insulin release in the rat. Am J Physiol 242: E280–E285

    PubMed  CAS  Google Scholar 

  • Berthoud H-R, Fox EA, Powley TL (1990) Localization of vagal preganglionics that stimulate insulin and glucagon secretion. Am J Physiol 258: R160–R168

    PubMed  CAS  Google Scholar 

  • Berthoud H-R, Carlson NR, Powley TL (1991) Topography of efferent vagal innervation of the rat gastrointestinal tract. Am J Physiol 260: R200–R207

    PubMed  CAS  Google Scholar 

  • Berthoud H-R, Kressel M, Neuhuber WL (1992) An anterograde tracing study of the vagal innervation of rat liver, portal vein and biliary system. Anat Embryol 186: 431–442

    Article  PubMed  CAS  Google Scholar 

  • Blackmore PF, Mojsov S, Exton JH, Habener JF (1991) Absence of insulinotropic glucagon-like peptide-1 (7–37) receptors on isolated rat liver hepatocytes. FEBS Lett 283: 7–10

    Article  PubMed  CAS  Google Scholar 

  • Blundell JE (1991) Pharmacological approaches to appetite suppression. Trends Pharmacol Sci 12: 147–157

    Article  PubMed  CAS  Google Scholar 

  • Braatvedt GD, Stanners A, Newrick PG, Halliwell M, Corrall RJM (1993) Evidence against a putative role for glucagon as a physiological splanchnic vasodilator in man. Clin Sci 84: 193–199

    PubMed  CAS  Google Scholar 

  • Brand CL, Rolin B, Jorgensen PN, Svendsen I, Kristensen JS, Holst JJ (1994) Immunoneutralization of endogenous glucagon with monoclonal glucagon antibody normalizes hyperglycaemia in moderately streptozotocin-diabetic rats. Diabetologia 37: 985–993

    Article  PubMed  CAS  Google Scholar 

  • Campfield LA, Smith FJ (1990) Systemic factors in the control of food intake. In: Stricker EM (ed) Neurobiology of food and fluid intake. Plenum, New York, pp 183–206 (Handbook of behavioral neurobiology, vol 10)

    Google Scholar 

  • Chiou GCY, Chuang CY (1988) Treatment of hypoglycemia with glucagon eye drops. J Ocular Pharm 4: 179–186

    Article  CAS  Google Scholar 

  • Clayton GW, Librik L (1963) Therapy of exogenous obesity in childhood and adolescence. Pediatr Clin North Am 10: 99–107

    PubMed  CAS  Google Scholar 

  • D’Almeida MS, Lautt WW (1991) Glucagon pharmacodynamics and modulation of sympathetic nerve and norepinephrine-induced constrictor responses in the superior mesenteric artery of the cat. J Pharmacol Exp Ther 259: 118–123

    PubMed  Google Scholar 

  • Day J, Johansen LK, Ganda OP, Soeldner JS, Gleason RE, Medgley W (1978) Factors governing insulin and glucagon response during normal meals. Clin Endocrinol (Oxf) 9: 443–454

    Article  CAS  Google Scholar 

  • DeCastro JM, Paullin SK, DeLugas GM (1978) Insulin and glucagon as determinants of body weight set point and microregulation in rats. J Comp Physiol Psychol 92: 571–579

    Article  CAS  Google Scholar 

  • Deetz LE, Wangsness PJ (1981) Influence of intrajugular administration of insulin, glucagon and propionate on voluntary feed intake of sheep. J Anim Sci 53: 427–433

    PubMed  CAS  Google Scholar 

  • DeJong A, Strubbe JH, Steffens AB (1977) Hypothalamic influence on insulin and glucagon release in the rat. Am J Physiol 233: E380–E388

    CAS  Google Scholar 

  • Denker H, Hedner P, Holst J, Tranberg KG (1975) Pancreatic glucagon response to an ordinary meal. Scand J Gastroenterol 10: 471–474

    Google Scholar 

  • Dinneen S, Alzaid A, Turk D, Rizza R (1995) Failure of glucagon suppression contributes to postprandial hyperglycaemia in IDDM. Diabetologia 38: 337–343

    Article  PubMed  CAS  Google Scholar 

  • Dourish CT, Rycroft W, Iversen SD (1989) Postponement of satiety by blockade of brain cholecystokinin (CCK-8) receptors. Science 245: 1509–1511

    Article  PubMed  CAS  Google Scholar 

  • Duss M (1986) Untersuchungen zur Sättingungswirkung von Glucagon. University of Zurich, Inaugural Dissertation. Maus, Konstanz

    Google Scholar 

  • Foster D (1984) From glycogen to ketones — and back. Diabetes 33: 1188–1199

    PubMed  CAS  Google Scholar 

  • Friedman MI, Ketchum M, Ulrich P, Breslin PAS, DellaCorte C (1994) Evidence for innervation of the hepatic parenchyma in the rat. Soc Neurosci Abstr 20: 1226 (abstract)

    Google Scholar 

  • Geary N (1987) Glucagon 1–21 fails to inhibit feeding. Peptides 8: 943–945

    Article  PubMed  CAS  Google Scholar 

  • Geary N (1990) Pancreatic glucagon signals postprandial satiety. Neurosci Biobehav Rev 14: 323–338

    Article  PubMed  CAS  Google Scholar 

  • Geary N (1995) A failure of pulsatile infusion to increase glucagon’s satiating potency. Physiol Behav 59: 613–616

    Article  Google Scholar 

  • Geary N, Smith GP (1982) Pancreatic glucagon fails to inhibit sham feeding in the rat. Peptides 3: 163–166

    Article  PubMed  CAS  Google Scholar 

  • Geary N, Smith GP (1983) Selective hepatic vagotomy blocks pancreatic glucagon’s satiety effect. Physiol Behav 31: 391–394

    Article  PubMed  CAS  Google Scholar 

  • Geary N, Farhoody N, Gersony A (1987) Food deprivation dissociates pancreatic glucagon’s effects on satiety and hepatic glucose production at dark onset. Physiol Behav 39: 507–511

    Article  PubMed  CAS  Google Scholar 

  • Geary N, Kissileff HR, Pi-Sunyer FX, Hinton V (1992) Individual, but not simultaneous, glucagon and cholecystokinin infusions inhibit feeding in men. Am J Physiol 262: R975–R980

    PubMed  CAS  Google Scholar 

  • Geary N, Le Sauter J, Noh N (1993) Glucagon acts in the liver to control spontaneous meal size in rats. Am J Physiol 264: R116–R122

    PubMed  CAS  Google Scholar 

  • Geary N, Asarian L, Langhans W (1995) Insulin does not increase glucagon’s potency to reduce meal size in spontaneously feeding rats. Soc Neurosci Abstr 21: 8 (abstract)

    Google Scholar 

  • Gutniak M, Grill V, Efendic S (1986) Effect of composition of mixed meals—low- versus high-carbohydrate content — on insulin, glucagon, and somatostatin release in healthy humans and in patients with NIDDM. Diabetes Care 9 (3): 244–249

    Article  PubMed  CAS  Google Scholar 

  • Hager J, Hansen L, Vaisse C, Vionnet N, Philippi A, Poller W, Velho G, Carcassi C, Contu L, Julier C, Cambien F, Passa P, Lathrop M, Kindsvogel W, Demenais F, Nishimura E, Froguel P (1995) A missense mutation in the glucagon receptor gene is associated with non-insulin-dependent diabetes mellitus. Nature Genet 9: 299–304

    Article  PubMed  CAS  Google Scholar 

  • Hildebrandt W, Blech W, Kohnert K-D (1991a) Kinetic studies on hepatic handling of glucagon using the model of non-recirculating perfused rat livers. Horm Metab Res 23: 410–413

    Article  PubMed  CAS  Google Scholar 

  • Hildebrandt W, Blech W, Kohnert K-D (1991b) Hepatische Reaktion auf pulsatile Anderungen der Pankreasglukagonkonzentration. Wiss Z Univ Halle 40: 137–149

    CAS  Google Scholar 

  • Hildebrandt W, Blech W, Kohnert K-D (1992) Amplitude smoothing and phase shifting effect of the isolated perfused rat liver on oscillating insulin and glucagon. Horm Metab Res 24: 345–346

    Article  PubMed  CAS  Google Scholar 

  • Holst JJ (1983) Glucagon in obesity. In: Lefèbvre PJ (ed) Glucagon II. Springer, Berlin Heidelberg New York, pp 507–521 (Handbook of experimental pharmacology, vol 66/II)

    Google Scholar 

  • Holst JJ, Schwartz TW, Lovgreen NA, Pedersen O, Beck-Nielsen H (1983) Diurnal profile of pancreatic polypeptide, pancreatic glucagon, gut glucagon and insulin in human morbid obesity. Int J Obes 7: 529–538

    PubMed  CAS  Google Scholar 

  • Howes GA, Forbes JM (1987) A role for the liver in the effects of glucagon on food intake in domestic fowl. Physiol Behav 39: 587–592

    Article  PubMed  CAS  Google Scholar 

  • Ishida R, Field JB (1983) Hepatic handling of glucagon. In: Lefèbvre PJ (ed) Glucagon II. Springer, Berlin Heidelberg New York, pp 361–388 (Handbook of experimental pharmacology, vol 66/II)

    Google Scholar 

  • Johnson PR, Greenwood MRC, Horwitz BA, Stern JS (1991) Animal models of obesity: genetic aspects. Annu Rev Nutr 11: 325–353

    Article  PubMed  CAS  Google Scholar 

  • Kalogeris TJ, Reidelberger RD, Mendel VE, Solomon TE (1991) Interaction of cholecystokinin-8 and pancreatic glucagon in control of food intake in dogs. Am J Physiol 260: R688–R692

    PubMed  CAS  Google Scholar 

  • Langhans W, Scharrer E (1987) Evidence for a role of the sodium pump of hepatocytes in the control of food intake. J Auton Nery Syst 20: 199–205

    Article  CAS  Google Scholar 

  • Langhans W, Scharrer E (1992) Metabolic control of eating, energy expenditure and the bioenergetics of obesity. In: Simopoulos AP (ed) World review of nutrition and dietetics. Karger, Basel, pp 1–67

    Google Scholar 

  • Langhans W, Geary N, Scharrer N (1982a) Liver glycogen content decreases during meals in rats. Am J Physiol 243: R450–R453

    PubMed  CAS  Google Scholar 

  • Langhans W, Zieger U, Scharrer E, Geary N (1982b) Stimulation of feeding in rats by intraperitoneal injection of antibodies to glucagon. Science 218: 894–896

    Article  PubMed  CAS  Google Scholar 

  • Langhans W, Pantel K, Muller-Schell W, Eggengerger E, Scharrer E (1984) Hepatic handling of pancreatic glucagon and glucose during meals in rats. Am J Physiol 247: R827–R832

    PubMed  CAS  Google Scholar 

  • Langhans W, Duss M, Scharrer E (1987) Decreased feeding and supraphysiological plasma levels of glucagon after glucagon injection in rats. Physiol Behav 41: 31–35

    Article  PubMed  CAS  Google Scholar 

  • Le Sauter J, Geary N (1991) Hepatic portal glucagon infusion decreases spontaneous meal size in rats. Am J physiol 261: R154–R161

    PubMed  Google Scholar 

  • Le Sauter J, Geary N (1993) Le glucagon pancréatique: signal physiologique de la satiété post prandiale. Ann Endocrinol 54: 149–161

    Google Scholar 

  • Le Sauter J, Noh U, Geary N (1991) Hepatic portal infusion of glucagon antibodies increases spontaneous meal size in rats. Am J Physiol 261: R162–R165

    PubMed  Google Scholar 

  • Lee JA, Ahmed Q, Burt AD (1992) Disappearance of hepatic parenchymal nerves in human liver cirrhosis. Gut 33: 87–91

    Article  PubMed  CAS  Google Scholar 

  • Levine S, Sievert CE, Morley JE, Gosnell BA, Silvis SE (1984) Peptidergic regulation of feeding in the dog (Canis familiaris). Peptides 5: 675–679

    Article  PubMed  CAS  Google Scholar 

  • Maclssac L, Geary N (1985) Partial liver denervations dissociate the inhibitory effects of pancreatic glucagon and epinephrine on feeding. Physiol Behav 35: 233–237

    Article  Google Scholar 

  • Madsen OD, Karlsen C, Blume N, Jensen HI, Larsson L-I, Holst JJ (1995) Transplantable glucagonomas derived from pluripotent rat islet tumor tissue cause severe anorexia and adipsia. Scand J Clin Lab Invest 55 [Suppl 220]: 27–36

    Google Scholar 

  • Martin JR, Novin D (1977) Decreased feeding in rats following hepatic-portal infusion of glucagon. Physiol Behav 19: 461–466

    Article  PubMed  CAS  Google Scholar 

  • Martin JR, Novin D, VanderWeele DA (1978) Loss of glucagon suppression of feeding after vagotomy in rats. Am J Physiol 234: E314–E318

    PubMed  CAS  Google Scholar 

  • McHugh P, Moran T, Barton GN (1975) A graded behavioral phenomenon regulating caloric intake. Science 190: 167–169

    Article  PubMed  CAS  Google Scholar 

  • McLaughlin CL, Gingerich RL, Baffle CA (1986) Role of glucagon in the control of food intake in Zucker obese and lean rats. Brain Res Bull 17: 419–426

    Article  PubMed  CAS  Google Scholar 

  • Miesner J, Smith GP, Gibbs J, Tyrka A (1992) Intravenous infusion of CCKA-receptor antagonist increases food intake in rats. Am J Physiol 262: R216–R219

    PubMed  CAS  Google Scholar 

  • Muller WA, Faloona GR, Aguilar-Parada E, Unger RH (1970) Abnormal alpha-cell function in diabetes. N Engl J Med 283: 109–115

    Article  PubMed  CAS  Google Scholar 

  • Nilsson G, Uvnas-Wallenstein K (1977) Effect of teasing and sham feeding on plasma glucagon concentration in dogs. Acta Physiol Scand 100: 298–302

    Article  PubMed  CAS  Google Scholar 

  • Palmer JP, Porte D Jr (1983) Neural control of glucagon secretion. In: Lefèbvre PJ (ed) Glucagon II. Springer, Berlin Heidelberg New York, pp 115–132 (Handbook of experimental pharmacology, vol 66/II)

    Google Scholar 

  • Penick SB, Hinkle LE Jr (1961) Depression of food intake induced in healthy subjects by glucagon. N Engl J Med 264: 893–897

    Article  PubMed  CAS  Google Scholar 

  • Polonsky KS, Jaspan JB, Rubenstein AH (1983) The metabolic clearance rate of glucagon. In: Lefèbvre PJ (ed) Glucagon II. Springer, Berlin Heidelberg New York, pp 353–359 (Handbook of experimental pharmacology, vol 66/11)

    Google Scholar 

  • Prechtl JC, Powley TL (1987) A light and electron microscopic examination of the vagal hepatic branch of the rat. Anat Embryol (Berl) 176: 115–126

    Article  CAS  Google Scholar 

  • Ritter S, Weatherford SC (1986) Capsaicin pretreatment blocks glucagon-induced suppression of food intake. Appetite 7: 291

    Google Scholar 

  • Ritter S, Weatherford SC, Stone SL (1986) Glucagon-induced inhibition of feeding is impaired by hepatic portal alloxan injection. Am J Physiol 250: R682–R690

    PubMed  CAS  Google Scholar 

  • Sawchenko PE, Friedman MI (1979) Sensory functions of the liver — a review. Am J Physiol 236: R5–R20

    PubMed  CAS  Google Scholar 

  • Scharrer E, Langhans W (1988) Metabolic and hormonal factors controlling food intake. Int J Vit Nutr Res 58: 249–261

    CAS  Google Scholar 

  • Schulman JL, Carleton JL, Whitney G, Whitehorn JC (1957) Effect of glucagon on food intake and body weight in man. J Appl Physiol 11: 419–421

    PubMed  CAS  Google Scholar 

  • Seifter S, Englard S (1993) Energy metabolism. In: Arias IM, Jakoby WB, Popper H, Schachter D, Shafritz DA (eds) The liver: biology and pathobiology. Raven, New York, pp 279–315

    Google Scholar 

  • Smith CJV, Bright-Taylor B (1974) Does a glucostatic mechanism for food intake control exist in chickens? Poultry Sci 53: 1720–1724

    CAS  Google Scholar 

  • Smith GP, Gibbs J (1992) The development and proof of the CCK hypothesis of satiety. In: Dourish CT, Cooper SJ, Iversen SD, Iversen LL (eds) Multiple cholecystokinin receptors in the CNS. Oxford University Press, Oxford, pp 166–182

    Google Scholar 

  • Stockinger Z, Geary N (1989) Pancreatic glucagon does not alter intrameal gastric emptying of milk in the rat. Physiol Behav 45: 1259–1261

    Article  PubMed  CAS  Google Scholar 

  • Strubbe JH, Wolsink JG, Schutte AM, Prins AJA (1989) Hepatic-portal and cardiac infusion of CCK-8 and glucagon induce different effects on feeding. Physiol Behav 46: 643–646

    Article  PubMed  CAS  Google Scholar 

  • Stunkard AJ, Van Itallie TB, Reis BB (1955) The mechanism of satiety: effect of glucagon on gastric hunger contractions in man. Proc Soc Exp Biol Med 89: 258–261

    PubMed  CAS  Google Scholar 

  • Taborsky GJ Jr (1989) The endocrine pancreas: control of secretion. In: Patton HD, Fuchs AF, Hille B, Scher AM, Steiner R (eds) Textbook of physiology, 21st edn. Saunders, Philadelphia, pp 1522–1543

    Google Scholar 

  • VanderWeele DA, Geiselman PJ, Novin D (1979) Pancreatic glucagon, food deprivation and feeding in intact and vagotomized rabbits. Physiol Behav 23: 155–158

    Article  PubMed  CAS  Google Scholar 

  • Wallace B, Lasker J (1993) Stand and deliver: getting peptide drugs into the body. Science 260: 912–915

    Article  PubMed  CAS  Google Scholar 

  • Weatherford SC, Ritter S (1986) Glucagon satiety: diurnal variation after hepatic branch vagotomy or intraportal alloxan. Br Res Bull 17: 545–549

    Article  CAS  Google Scholar 

  • Weatherford SC, Ritter S (1988) Lesion of vagal afferent terminals impairs glucagoninduced suppression of food intake. Physiol Behav 43: 645–650

    Article  PubMed  CAS  Google Scholar 

  • Weick BG, Ritter S (1986a) Dose-related suppression of feeding by intraportal glucagon infusion in the rat. Am J Physiol 250: R676–R681

    PubMed  CAS  Google Scholar 

  • Weick BG, Ritter S (1986b) Stimulation of insulin release and suppression of feeding by hepatic portal glucagon. Physiol Behav 38: 531–536

    Article  PubMed  CAS  Google Scholar 

  • Weigle DS (1987) Pulsatile secretion of fuel-regulatory hormones. Diabetes 36: 764–775

    PubMed  CAS  Google Scholar 

  • Wynick D, Hammond P, Bloom S (1993) The glucagonoma syndrome. Clin Dermatol 11: 93–97

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. N. Geary
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Medicine, Centre Hospitalier Universitaire de Liège, B-4000, Liège 1, Belgium

    Pierre J. Lefèbvre M.D., Ph.D., FRCP

  2. Division of Diabetes, Nutrition, and Metabolic Disorders, C.H.U. Sart Tilman, B-4000, Liège 1, Belgium

    Pierre J. Lefèbvre M.D., Ph.D., FRCP

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Geary, N. (1996). Glucagon and the Control of Appetite. In: Lefèbvre, P.J. (eds) Glucagon III. Handbook of Experimental Pharmacology, vol 123. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-61150-6_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-61150-6_14

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-64718-5

  • Online ISBN: 978-3-642-61150-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation