Skip to main content
View expanded cover

Glucagon II pp 223–237Cite as

Glucagon and Starvation

  • Chapter

Part of the Handbook of Experimental Pharmacology book series (HEP,volume 66 / 2)

Abstract

When food supply is interrupted, survival is dependent upon a highly integrated metabolic response directed at maintaining glucose homeostasis and conserving body protein. Initially, the predominant metabolic requirement is the maintenance of a continuing supply of blood glucose for utilization by obligate glucose-consuming tissues, especially brain. Because liver glycogen stores are rapidly exhausted, continuing hepatic glucose production to maintain normoglycemia depends on an early acceleration of hepatic gluconeogenesis. However, since amino acids represent the sole precursors for de novo glucose synthesis, the demand for continuing glucose production imposes a steady drain on the body’s protein stores. Inasmuch as significant depletion of body protein (beyond 30%–50%) is generally fatal, survival during prolonged starvation ultimately depends upon a reduction of glucose consumption and a shift toward maximal utilization of fat, the body’s major storage fuel. The overall response to starvation may thus be characterized as biphasic, with the early, gluconeogenic phase most pronounced during the first 3–5 days, and the later, protein-conserving phase dominating after 2–4 weeks (Saudek and Felig 1976).

Keywords

  • Glucose Production
  • Ketone Body
  • Hepatic Glucose Production
  • Insulin Deficiency
  • Hepatic Gluconeogenesis

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-3-642-69019-8_12
  • Chapter length: 15 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   139.00
Price excludes VAT (USA)
  • ISBN: 978-3-642-69019-8
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   179.99
Price excludes VAT (USA)

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Altszuler N, Gottlieb B, Hampshire J (1976) Interaction of somatostatin, glucagon, and insulin on hepatic glucose output in the normal dog. Diabetes 25: 116–121

    PubMed  CrossRef  CAS  Google Scholar 

  • Benedict FG (1915) A study of prolonged fasting. Publication No 203. Carnegie Institute, Washington, DC

    Google Scholar 

  • Burman KD, Smalleridge RC, Jones L, Ramos EA, O’Brian JT, Wright FD, Wartofsky L (1980) Glucagon kinetics in fasting: physiological elevations in serum 3,5,3′-triiodothyronine increase the metabolic clearance rate of glucagon. J Clin Endocrinol Metab 51: 1158–1165

    PubMed  CrossRef  CAS  Google Scholar 

  • Cahill GF Jr (1970) Starvation in man. N Engl J Med 282: 668–675

    PubMed  CrossRef  CAS  Google Scholar 

  • Cahill GF Jr (1971) Physiology of insulin in man. Diabetes 20: 785–799

    PubMed  CAS  Google Scholar 

  • Cahill GF Jr, Herrera MG, Morgan AP, Soeldner JS, Steinke J, Levy PL, Reich GA Jr, Kipnis DM (1966) Hormone-fuel interrelationships during fasting. J Clin Invest 45: 1751–1769

    PubMed  CrossRef  CAS  Google Scholar 

  • Cherrington AD, Chiasson JL, Liljenquist JE, Jennings AS, Keller U, Lacy WW (1976) The role of insulin and glucagon in the regulation of basal glucose production in the postabsorptive dog. J Clin Invest 58: 1407–1418

    PubMed  CrossRef  CAS  Google Scholar 

  • Cherrington AD, Lacy WW, Chiasson JL (1978) Effect of glucagon on glucose production during insulin deficiency in the dog. J Clin Invest 62: 664–677

    PubMed  CrossRef  CAS  Google Scholar 

  • Cherrington AD, Liljenquist JE, Shulman GI, Williams P, Lacy WW (1979) Importance of hypoglycemia-induced glucose production during isolated glucagon deficiency. Am J Physiol 236: E263–E271

    PubMed  CAS  Google Scholar 

  • Cherrington AD, Williams PE, Shulman GI, Lacy WW (1981) Differential time course of glucagon’s effect on glycogenolysis and gluconeogenesis in the conscious dog. Diabetes 30: 1980–1987

    CrossRef  Google Scholar 

  • Chiasson JL, Cook J, Liljenquist JE, Lacy WW (1974) Glucagon stimulation of gluconeogenesis from alanine in the intact dog. Am J Physiol 227: 19–23

    PubMed  CAS  Google Scholar 

  • Chiasson JL, Liljenquist JE, Sinclair-Smith BC, Lacy WW (1975) Gluconeogenesis from alanine in normal postabsorptive man: intrahepatic stimulatory effect of glucagon. Diabetes 24: 574–584

    PubMed  CrossRef  CAS  Google Scholar 

  • Chiasson JL, Liljenquist JE, Lacy WW, Jennings AS, Cherrington AD (1977) Gluconeogenesis: methodological approaches in vivo. Fed Proc 36: 229–235

    PubMed  CAS  Google Scholar 

  • DeFronzo RA, Soman V, Sherwin RS, Hendler R, Felig P (1978) Insulin binding to monocytes and insulin action in human obesity, starvation, and refeeding. J Clin Invest 62: 204–213

    PubMed  CrossRef  CAS  Google Scholar 

  • Felig P (1973) The glucose-alanine cycle. Metabolism 22: 179–207

    PubMed  CrossRef  CAS  Google Scholar 

  • Felig P, Owen OE, Wahren J, Cahill GF Jr (1969 a) Amino acid metabolism during prolonged starvation. J Clin Invest 48: 584–594

    Google Scholar 

  • Felig P, Marliss E, Owen OE, Cahill GF Jr (1969 b) Role of substrate in the regulation of hepatic gluconeogenesis. Adv Enzyme Regul 7: 41–46

    Google Scholar 

  • Felig P, Pozefsky T, Marliss E, Cahill GF Jr (1970) Alanine: key role in gluconeogenesis. Science 167: 1003–1004

    PubMed  CrossRef  CAS  Google Scholar 

  • Fisher M, Sherwin RS, Hendler R, Felig P (1976) Kinetics of glucagon in man: effects of starvation. Proc Natl Acad Sei USA 73: 1734–1739

    Google Scholar 

  • Garber AJ, Menzel PH, Boden G, Owen OE (1974) Hepatic ketogenesis and gluconeogenesis in humans. J Clin Invest 54: 981–989

    PubMed  CrossRef  CAS  Google Scholar 

  • Gerich JE, Lorenzi M, Bier DM, Schneider V, Tsalikian E, Karam JH, Forsham PH (1975) Prevention of human diabetic ketoacidosis by somatostatin. N Engl J Med 292: 985–989

    PubMed  CrossRef  CAS  Google Scholar 

  • Hultman E, Nilsson LH (1971) Liver glycogen in man: effect of different diets and muscular exercise. Adv Exp Med Biol 11: 143–151

    Google Scholar 

  • Keller U, Chiasson JL, Liljenquist JE, Cherrington AD, Jennings AS, Crofford OB (1977) The roles of insulin, glucagon, and free fatty acids in the regulation of ketogenesis in dogs. Diabetes 26: 1040–1051

    PubMed  CAS  Google Scholar 

  • Keys A, Brozck J, Henschel A, Mickelson O, Taylor HL (1950) The biology of human starvation. University of Minnesota Press, Minneapolis

    Google Scholar 

  • Lilavivathana V, Campbell RG, Brodows RG (1978) Control of insulin secretion during fasting in man. Metabolism 27: 815–821

    PubMed  CrossRef  CAS  Google Scholar 

  • Liljenquist JE, Mueller GL, Cherrington AD, Keller U, Chiasson JL, Perry JM, Lacy WW, Rabinowitz D (1977) Evidence for an important role of glucagon in the regulation of hepatic glucose production in normal man. J Clin Invest 59: 369–374

    PubMed  CrossRef  CAS  Google Scholar 

  • Mallette LE, Exton JH, Park CR (1969) Control of gluconeogenesis from amino acids in the perfused rat liver. J Biol Chem 244: 5713–5723

    CAS  Google Scholar 

  • Marliss EB, Aoki TT, Unger RH, Soldner S, Cahill GF Jr (1970) Glucagon levels and metabolic effects in fasting man. J Clin Invest 49: 2256–2271

    PubMed  CrossRef  CAS  Google Scholar 

  • McGarry JD (1979) New perspectives in the regulation of ketogenesis. Diabetes 28: 517–523

    PubMed  CAS  Google Scholar 

  • McGarry JD, Foster DW (1976) Ketogenesis and its regulation. Am J Med 61: 9–13

    PubMed  CrossRef  CAS  Google Scholar 

  • McGarry JD, Foster DW (1977) Hormonal control of ketogenesis: biochemical considerations. Arch Intern Med 137: 495–501

    PubMed  CrossRef  CAS  Google Scholar 

  • McGarry JD, Foster DW (1981) Ketogenesis. In: Unger RH, Orci L (eds) Glucagon: physiology, pathophysiology, and morphology of the pancreatic A-cells. Elsevier, New York, p 273

    Google Scholar 

  • McGarry JD, Wright P, Foster D (1975) Hormonal control of ketogenesis: rapid activation of hepatic ketogenic capacity in fed rats by antiinsulin serum and glucagon. J Clin Invest 55: 1202–1209

    PubMed  CrossRef  CAS  Google Scholar 

  • Miles J, Nissen S, Haymond D (1981) Interaction of insulin, glucagon, and free fatty acids on ketone body production in man. Diabetes [Suppl 1] 30: 63A

    Google Scholar 

  • Owen OE, Reichard GA Jr (1971) Human forearm metabolism during progressive starvation. J Clin Invest 50: 1536–1545

    PubMed  CrossRef  CAS  Google Scholar 

  • Owen OE, Morgan AP, Kemp HG, Sullivan JM, Herrera MG, Cahill GF Jr (1967) Brain metabolism during fasting. J Clin Invest 46: 1589–1595

    PubMed  CrossRef  CAS  Google Scholar 

  • Owen OE, Felig P, Morgan AP, Wahren J, Cahill GF Jr (1969) Liver and kidney metabolism during prolonged starvation. J Clin Invest 48: 574–583

    PubMed  CrossRef  CAS  Google Scholar 

  • Palaiologos G, Felig P (1976) Effects of ketone bodies on amino acid metabolism in isolated rat diaphragm. Biochem J 154: 709–716

    PubMed  CAS  Google Scholar 

  • Pozefsky T, Tancredi RG, Moxley RT, Dupre J, Tobin JD (1976 a) Effects of brief starvation on muscle amino acid metabolism in nonobese man. J Clin Invest 57: 444–449

    Google Scholar 

  • Pozefsky T, Tancredi RG, Moxley RT, Dupre J, Tobin JD (1976 b) Metabolism of forearm tissues in man: studies with glucagon. Diabetes 25: 128–135

    Google Scholar 

  • Reinmuth OM, Scheinberg P, Bourne B (1965) Total cerebral blood flow and metabolism. Arch Neurol 12: 49–66

    Google Scholar 

  • Sacca L, Sherwin R, Hendler R, Felig P (1979) Influence of continuous physiologic hyperinsulinemia on glucose kinetics and counterregulatory hormones in normal and diabetic humans. J Clin Invest 63: 849–857

    PubMed  CrossRef  CAS  Google Scholar 

  • Sacca L, Yigorito C, Cicala M, Ungaro B, Sherwin RS (1982) Mechanisms of epinephrine-induced glucose intolerance in normal humans: role of the splanchnic bed. J Clin Invest 69: 284–293

    PubMed  CrossRef  CAS  Google Scholar 

  • Saudek CD, Felig P (1976) The metabolic events of starvation. Am J Med 60: 117–126

    PubMed  CrossRef  CAS  Google Scholar 

  • Schade DS, Eaton RP (1975) Glucagon regulation of plasma ketone body concentration in human diabetes. J Clin Invest 56: 1340–1344, 1975

    Google Scholar 

  • Schade DS, Eaton RP (1976) Modulation of fatty acid metabolism by glucagon in man. IV. Effects of a physiologic hormone infusion in normal man. Diabetes 25: 978–983

    Google Scholar 

  • Schneider SH, Fineberg SE, Blackburn GL (1981) The acute metabolic effects of glucagon and its interactions with insulin in forearm tissue. Diabetologia 20: 616–624

    PubMed  CrossRef  CAS  Google Scholar 

  • Sherwin RS, Felig P (1981) Hypoglycemia. In: Felig P, Baxter JD, Broadus AE, Frohmann LA (eds) Endocrinology and metabolism. McGraw-Hill, New York, p 869

    Google Scholar 

  • Sherwin RS, Hendler R, Felig P (1975) Effect of ketone infusions on amino acid and nitrogen metabolism in man. J Clin Invest 55: 1382–1390

    PubMed  CrossRef  CAS  Google Scholar 

  • Sherwin RS, Hendler RG, Felig P (1976) Effect of diabetes mellitus and insulin on the turnover and metabolic response to ketones in man. Diabetes 25: 776–784

    PubMed  CrossRef  CAS  Google Scholar 

  • Sherwin RS, Hendler R, DeFronzo R, Wahren J, Felig P (1977 a) Glucose homeostatis during prolonged suppression of glucagon and insulin secretion by somatostatin. Proc Natl Acad Sei USA 74: 348–352

    Google Scholar 

  • Sherwin RS, Tamborlane W, Hendler R, Sacca L, DeFronzo RA, Felig P (1977 b) Influence of glucagon replacement on the hyperglycemic and hyperketonemic response to prolonged somatostatin infusion in normal man. J Clin Endocrinol Metab 45: 1104–1107

    Google Scholar 

  • Shulman GI, Lacy WW, Liljenquist JE, Keller U, Williams PE, Cherrington AD (1980) Effect of glucose, independent of changes in insulin and glucagon secretion, on alanine metabolism in the conscious dog. J Clin Invest 65: 496–505, 1980

    Google Scholar 

  • Vagenakis AG, Burger A, Portnay GI, Rudolph M, O’Brian JT, Azizi F, Arky RA, Nicod P, Ingbar SH, Braverman LE (1975) Diversion of peripheral thyroxine metabolism from activating to inactivating pathways during complete fasting. J Clin Endocrinol Metab 44: 1002–1005

    Google Scholar 

  • Wahren J, Efendic S, Luft R, Hagenfeldt L, Bjorkman O, Felig P (1977) Influence of somatostatin on splanchnic glucose metabolism in postabsorptive and 60-hour fasted humans. J Clin Invest 59: 299–307

    PubMed  CrossRef  CAS  Google Scholar 

  • Williamson JR, Kreisberg RA, Felts PW (1966) Mechanism for the stimulation of gluconeogenesis by fatty acids in perfused rat liver. Proc Natl Acad Sei USA 56: 247–254

    CrossRef  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 1983 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Gelfand, R.A., Sherwin, R.S. (1983). Glucagon and Starvation. In: Lefebvre, P.J. (eds) Glucagon II. Handbook of Experimental Pharmacology, vol 66 / 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-69019-8_12

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-69019-8_12

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-69021-1

  • Online ISBN: 978-3-642-69019-8

  • eBook Packages: Springer Book Archive