Role of insulin in the regulation of leucine kinetics in the conscious dog

N. N. Abumrad, L. S. Jefferson, S. R. Rannels, P. E. Williams, A. D. Cherrington, W. W. Lacy

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Abstract

To study the effect of insulin on leucine kinetics, three groups of conscious dogs were studied after an overnight fast (16-18 h). One, saline-infused group (n = 5), served as control. The other two groups were infused with somatostatin and constant replacement amount of glucagon; one group (n = 6) received no insulin replacement, to produce acute insulin deficiency, and the other (n = 6) was constantly replaced with 600 μU/kg per min insulin, to produce twice basal hyperinsulinemia. Hepatic and extrahepatic splanchnic (gut) balance of leucine and α-ketoisocaproate (KIC) were calculated using the arteriovenous difference technique. L,4,5,[3H]Leucine was used to measure the rates (micromoles per kilogram per minute) of appearance (Ra) and disappearance (Rd), and clearance (Cl) of plasma leucine (milliliters per kilogram per minute). Saline infusion for 7 h resulted in isotopic steady state, where Ra and Rd were equal (3.2±0.2 μmol/kg per min). Acute insulin withdrawal of 4-h duration caused the plasma leucine to increase by 40% (P < 0.005). This change was caused by a decrease in the outflow of leucine (Cl) from the plasma, since Ra did not change. The net hepatic release of the amino acid (0.24±0.03 μmol/kg per min) did not change significantly; the arterio-deep femoral venous differences of leucine (-10±1 μmol/liter) and KIC (-12±2 μmol/liter) did not change significantly indicating net release of the amino and ketoacids across the hindlimb. Selective twice basal hyperinsulinemia resulted in a 36% drop in plasma leucine (from control levels of 128±8 to 82±7 μmol/liter, P < 0.005) within 4 h. This was accompanied by a 15% reduction in Ra and a 56% rise in clearance (P < 0.001, both). Net hepatic leucine production and net release of leucine and KIC across the hindlimb fell markedly. These studies indicate that physiologic changes in circulating insulin levels result in a differential dose-dependent effect on total body leucine metabolism in the intact animal. Acute insulin withdrawal exerts no effect on leucine rate of appearance, while at twice basal levels, insulin inhibited leucine rate of appearance and stimulated its rate of disappearance.

Original languageEnglish (US)
Pages (from-to)1031-1041
Number of pages11
JournalUnknown Journal
Volume70
Issue number5
DOIs
StatePublished - Jan 1 1982

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Leucine
Dogs
Insulin
Hyperinsulinism
Hindlimb
Liver
Viscera
Thigh
Somatostatin
Glucagon
Amino Acids

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Abumrad, N. N., Jefferson, L. S., Rannels, S. R., Williams, P. E., Cherrington, A. D., & Lacy, W. W. (1982). Role of insulin in the regulation of leucine kinetics in the conscious dog. Unknown Journal, 70(5), 1031-1041. https://doi.org/10.1172/JCI110690
Abumrad, N. N. ; Jefferson, L. S. ; Rannels, S. R. ; Williams, P. E. ; Cherrington, A. D. ; Lacy, W. W. / Role of insulin in the regulation of leucine kinetics in the conscious dog. In: Unknown Journal. 1982 ; Vol. 70, No. 5. pp. 1031-1041.
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Abumrad, NN, Jefferson, LS, Rannels, SR, Williams, PE, Cherrington, AD & Lacy, WW 1982, 'Role of insulin in the regulation of leucine kinetics in the conscious dog', Unknown Journal, vol. 70, no. 5, pp. 1031-1041. https://doi.org/10.1172/JCI110690

Role of insulin in the regulation of leucine kinetics in the conscious dog. / Abumrad, N. N.; Jefferson, L. S.; Rannels, S. R.; Williams, P. E.; Cherrington, A. D.; Lacy, W. W.

In: Unknown Journal, Vol. 70, No. 5, 01.01.1982, p. 1031-1041.

Research output: Contribution to journalArticle

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AU - Abumrad, N. N.

AU - Jefferson, L. S.

AU - Rannels, S. R.

AU - Williams, P. E.

AU - Cherrington, A. D.

AU - Lacy, W. W.

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Y1 - 1982/1/1

N2 - To study the effect of insulin on leucine kinetics, three groups of conscious dogs were studied after an overnight fast (16-18 h). One, saline-infused group (n = 5), served as control. The other two groups were infused with somatostatin and constant replacement amount of glucagon; one group (n = 6) received no insulin replacement, to produce acute insulin deficiency, and the other (n = 6) was constantly replaced with 600 μU/kg per min insulin, to produce twice basal hyperinsulinemia. Hepatic and extrahepatic splanchnic (gut) balance of leucine and α-ketoisocaproate (KIC) were calculated using the arteriovenous difference technique. L,4,5,[3H]Leucine was used to measure the rates (micromoles per kilogram per minute) of appearance (Ra) and disappearance (Rd), and clearance (Cl) of plasma leucine (milliliters per kilogram per minute). Saline infusion for 7 h resulted in isotopic steady state, where Ra and Rd were equal (3.2±0.2 μmol/kg per min). Acute insulin withdrawal of 4-h duration caused the plasma leucine to increase by 40% (P < 0.005). This change was caused by a decrease in the outflow of leucine (Cl) from the plasma, since Ra did not change. The net hepatic release of the amino acid (0.24±0.03 μmol/kg per min) did not change significantly; the arterio-deep femoral venous differences of leucine (-10±1 μmol/liter) and KIC (-12±2 μmol/liter) did not change significantly indicating net release of the amino and ketoacids across the hindlimb. Selective twice basal hyperinsulinemia resulted in a 36% drop in plasma leucine (from control levels of 128±8 to 82±7 μmol/liter, P < 0.005) within 4 h. This was accompanied by a 15% reduction in Ra and a 56% rise in clearance (P < 0.001, both). Net hepatic leucine production and net release of leucine and KIC across the hindlimb fell markedly. These studies indicate that physiologic changes in circulating insulin levels result in a differential dose-dependent effect on total body leucine metabolism in the intact animal. Acute insulin withdrawal exerts no effect on leucine rate of appearance, while at twice basal levels, insulin inhibited leucine rate of appearance and stimulated its rate of disappearance.

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Abumrad NN, Jefferson LS, Rannels SR, Williams PE, Cherrington AD, Lacy WW. Role of insulin in the regulation of leucine kinetics in the conscious dog. Unknown Journal. 1982 Jan 1;70(5):1031-1041. https://doi.org/10.1172/JCI110690