Effects of free fatty acids, insulin, glucagon and adrenaline on ketone body production in humans.

J. M. Miles, M. W. Haymond, J. E. Gerich

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

In normal human subjects, when plasma insulin, glucagon and growth hormone were 'clamped' at basal concentrations (by infusion of somatostatin plus replacement infusion of these hormones), infusion of Intralipid and heparin increased plasma free fatty acid (FFA) concentrations to approx. 1.3 mM, and ketone body production increased 4-5 fold to approx. 11 mumol . kg -1 . min-1. Hyperglucagonaemia did not further increase ketogenesis. In conditions of combined insulin and glucagon deficiency (by infusion of somatostatin without insulin and glucagon), administration of Intralipid and heparin increased plasma FFA concentrations to approx. 2.2 mM but a further increase in ketone body production did not accompany this increase. In these conditions hyperglucagonaemia increased ketogenesis by 2-3 fold the increment seen in control studies. Infusion of adrenaline (epinephrine) in conditions in which insulin secretion was not inhibited caused only a transient increase in plasma FFA concentrations and in ketone body production. These data indicate: (1) that in humans increased FFA availability can markedly augment ketogenesis in the absence of insulin deficiency and without hyperglucagonaemia; (2) that glucagon can increase ketone body production during insulin deficiency but not in its absence; and (3) that insulin deficiency may be accompanied by increased ketogenesis only because of a lack of its restraint on lipolysis and because of the action of glucagon. Glucagon may be important in determining the magnitude of ketone body production for a given degree of FFA availability and insulin deficiency, and may be necessary for attainment of maximal rates of ketogenesis. Adrenaline increases ketone body production in humans, but whether this is primarily due to a direct effect on the liver or is mediated through enhancement of lipolysis remains to be determined.

Original languageEnglish (US)
Pages (from-to)192-213
Number of pages22
JournalCiba Foundation symposium
Volume87
StatePublished - 1982
Externally publishedYes

Fingerprint

Ketone Bodies
Glucagon
Nonesterified Fatty Acids
Epinephrine
Insulin
Lipolysis
Somatostatin
Heparin
Growth Hormone
Hormones
Liver

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effects of free fatty acids, insulin, glucagon and adrenaline on ketone body production in humans. / Miles, J. M.; Haymond, M. W.; Gerich, J. E.

In: Ciba Foundation symposium, Vol. 87, 1982, p. 192-213.

Research output: Contribution to journalArticle

Miles, J. M. ; Haymond, M. W. ; Gerich, J. E. / Effects of free fatty acids, insulin, glucagon and adrenaline on ketone body production in humans. In: Ciba Foundation symposium. 1982 ; Vol. 87. pp. 192-213.
@article{3e84c4cfe20747ef9370e41d9134e91d,
title = "Effects of free fatty acids, insulin, glucagon and adrenaline on ketone body production in humans.",
abstract = "In normal human subjects, when plasma insulin, glucagon and growth hormone were 'clamped' at basal concentrations (by infusion of somatostatin plus replacement infusion of these hormones), infusion of Intralipid and heparin increased plasma free fatty acid (FFA) concentrations to approx. 1.3 mM, and ketone body production increased 4-5 fold to approx. 11 mumol . kg -1 . min-1. Hyperglucagonaemia did not further increase ketogenesis. In conditions of combined insulin and glucagon deficiency (by infusion of somatostatin without insulin and glucagon), administration of Intralipid and heparin increased plasma FFA concentrations to approx. 2.2 mM but a further increase in ketone body production did not accompany this increase. In these conditions hyperglucagonaemia increased ketogenesis by 2-3 fold the increment seen in control studies. Infusion of adrenaline (epinephrine) in conditions in which insulin secretion was not inhibited caused only a transient increase in plasma FFA concentrations and in ketone body production. These data indicate: (1) that in humans increased FFA availability can markedly augment ketogenesis in the absence of insulin deficiency and without hyperglucagonaemia; (2) that glucagon can increase ketone body production during insulin deficiency but not in its absence; and (3) that insulin deficiency may be accompanied by increased ketogenesis only because of a lack of its restraint on lipolysis and because of the action of glucagon. Glucagon may be important in determining the magnitude of ketone body production for a given degree of FFA availability and insulin deficiency, and may be necessary for attainment of maximal rates of ketogenesis. Adrenaline increases ketone body production in humans, but whether this is primarily due to a direct effect on the liver or is mediated through enhancement of lipolysis remains to be determined.",
author = "Miles, {J. M.} and Haymond, {M. W.} and Gerich, {J. E.}",
year = "1982",
language = "English (US)",
volume = "87",
pages = "192--213",
journal = "Ciba Foundation symposium",
issn = "0300-5208",
publisher = "Wiley Subscription Services",

}

TY - JOUR

T1 - Effects of free fatty acids, insulin, glucagon and adrenaline on ketone body production in humans.

AU - Miles, J. M.

AU - Haymond, M. W.

AU - Gerich, J. E.

PY - 1982

Y1 - 1982

N2 - In normal human subjects, when plasma insulin, glucagon and growth hormone were 'clamped' at basal concentrations (by infusion of somatostatin plus replacement infusion of these hormones), infusion of Intralipid and heparin increased plasma free fatty acid (FFA) concentrations to approx. 1.3 mM, and ketone body production increased 4-5 fold to approx. 11 mumol . kg -1 . min-1. Hyperglucagonaemia did not further increase ketogenesis. In conditions of combined insulin and glucagon deficiency (by infusion of somatostatin without insulin and glucagon), administration of Intralipid and heparin increased plasma FFA concentrations to approx. 2.2 mM but a further increase in ketone body production did not accompany this increase. In these conditions hyperglucagonaemia increased ketogenesis by 2-3 fold the increment seen in control studies. Infusion of adrenaline (epinephrine) in conditions in which insulin secretion was not inhibited caused only a transient increase in plasma FFA concentrations and in ketone body production. These data indicate: (1) that in humans increased FFA availability can markedly augment ketogenesis in the absence of insulin deficiency and without hyperglucagonaemia; (2) that glucagon can increase ketone body production during insulin deficiency but not in its absence; and (3) that insulin deficiency may be accompanied by increased ketogenesis only because of a lack of its restraint on lipolysis and because of the action of glucagon. Glucagon may be important in determining the magnitude of ketone body production for a given degree of FFA availability and insulin deficiency, and may be necessary for attainment of maximal rates of ketogenesis. Adrenaline increases ketone body production in humans, but whether this is primarily due to a direct effect on the liver or is mediated through enhancement of lipolysis remains to be determined.

AB - In normal human subjects, when plasma insulin, glucagon and growth hormone were 'clamped' at basal concentrations (by infusion of somatostatin plus replacement infusion of these hormones), infusion of Intralipid and heparin increased plasma free fatty acid (FFA) concentrations to approx. 1.3 mM, and ketone body production increased 4-5 fold to approx. 11 mumol . kg -1 . min-1. Hyperglucagonaemia did not further increase ketogenesis. In conditions of combined insulin and glucagon deficiency (by infusion of somatostatin without insulin and glucagon), administration of Intralipid and heparin increased plasma FFA concentrations to approx. 2.2 mM but a further increase in ketone body production did not accompany this increase. In these conditions hyperglucagonaemia increased ketogenesis by 2-3 fold the increment seen in control studies. Infusion of adrenaline (epinephrine) in conditions in which insulin secretion was not inhibited caused only a transient increase in plasma FFA concentrations and in ketone body production. These data indicate: (1) that in humans increased FFA availability can markedly augment ketogenesis in the absence of insulin deficiency and without hyperglucagonaemia; (2) that glucagon can increase ketone body production during insulin deficiency but not in its absence; and (3) that insulin deficiency may be accompanied by increased ketogenesis only because of a lack of its restraint on lipolysis and because of the action of glucagon. Glucagon may be important in determining the magnitude of ketone body production for a given degree of FFA availability and insulin deficiency, and may be necessary for attainment of maximal rates of ketogenesis. Adrenaline increases ketone body production in humans, but whether this is primarily due to a direct effect on the liver or is mediated through enhancement of lipolysis remains to be determined.

UR - http://www.scopus.com/inward/record.url?scp=0020009902&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020009902&partnerID=8YFLogxK

M3 - Article

C2 - 7042239

AN - SCOPUS:0020009902

VL - 87

SP - 192

EP - 213

JO - Ciba Foundation symposium

JF - Ciba Foundation symposium

SN - 0300-5208

ER -