Human skeletal muscle metabolism during hyperinsulinemic-hyperglycemia

L. S. Sidossis, G. D. Lopaschuk, S. Klein, R. R. Wolfe

Research output: Contribution to journalArticle

Abstract

Our goal was to examine changes in muscle acetyl-CoA, long-chain acylcarnitine (LCA), and short-chain acylcamitine (SCA) concentrations in response to hyrerinsulinemic-hyperglycemia. Seven healthy volunteers had a muscle biopsy taken from the lateral aspect of the vastus lateralis muscle approximately 15 cm above the patella, in the morning after they had fasted overnight (basal). Immediately following the basal period a hyperinsulinemic-hyperglycemic clamp (insulin=275 μU/mL, glucose=140 mg/dL) was started and continued for 5 h. Plasma FFA concentration was kept constant by means of variable infusions of Intralipid and heparin. A second muscle biopsy was taken from the same incision site at the end of the study. Carbohydrate oxidation significantly increased during the clamp (5.1±1.3 to 26.8±3.0 nmol/kg.min, P<0.01). However, despite the significant increase in pyruvate flux through pyruvate dehydrogenase, we did not observe any significant change in the acetyl-CoA-to-CoA ratio, suggesting that the contribution of β-oxidation-derived acetyl-CoA decreased during the clamp. The significant decrease in SCA concentration (5064±1776 to 2192±448 nmol/g dry wt., P<0.05), suggested that fatty acid oxidation was limited at a step preceding β-oxidation. This was confirmed by the observed decrease in LCA concentration during the clamp (855±270 to 377±83 nmol/g dry wt, P<0.05), in concert with the notion that high pyruvate flux blocks fatty acid entry into the mitochondria via inhibition of carnitine palmitoyltransferase I. (Supported by NIH grants DK-34817 and DK-46017 and Shriners Hospital grant 15849. ).

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number3
StatePublished - 1996

Fingerprint

Clamping devices
hyperglycemia
Metabolism
Hyperglycemia
Acetyl Coenzyme A
Muscle
skeletal muscle
Skeletal Muscle
Pyruvic Acid
Muscles
Oxidation
muscles
metabolism
Biopsy
Organized Financing
oxidation
pyruvate dehydrogenase (lipoamide)
biopsy
Fatty Acids
Fluxes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Sidossis, L. S., Lopaschuk, G. D., Klein, S., & Wolfe, R. R. (1996). Human skeletal muscle metabolism during hyperinsulinemic-hyperglycemia. FASEB Journal, 10(3).

Human skeletal muscle metabolism during hyperinsulinemic-hyperglycemia. / Sidossis, L. S.; Lopaschuk, G. D.; Klein, S.; Wolfe, R. R.

In: FASEB Journal, Vol. 10, No. 3, 1996.

Research output: Contribution to journalArticle

Sidossis, LS, Lopaschuk, GD, Klein, S & Wolfe, RR 1996, 'Human skeletal muscle metabolism during hyperinsulinemic-hyperglycemia', FASEB Journal, vol. 10, no. 3.
Sidossis LS, Lopaschuk GD, Klein S, Wolfe RR. Human skeletal muscle metabolism during hyperinsulinemic-hyperglycemia. FASEB Journal. 1996;10(3).
Sidossis, L. S. ; Lopaschuk, G. D. ; Klein, S. ; Wolfe, R. R. / Human skeletal muscle metabolism during hyperinsulinemic-hyperglycemia. In: FASEB Journal. 1996 ; Vol. 10, No. 3.
@article{becedc8408c6481e808236624a11ecfd,
title = "Human skeletal muscle metabolism during hyperinsulinemic-hyperglycemia",
abstract = "Our goal was to examine changes in muscle acetyl-CoA, long-chain acylcarnitine (LCA), and short-chain acylcamitine (SCA) concentrations in response to hyrerinsulinemic-hyperglycemia. Seven healthy volunteers had a muscle biopsy taken from the lateral aspect of the vastus lateralis muscle approximately 15 cm above the patella, in the morning after they had fasted overnight (basal). Immediately following the basal period a hyperinsulinemic-hyperglycemic clamp (insulin=275 μU/mL, glucose=140 mg/dL) was started and continued for 5 h. Plasma FFA concentration was kept constant by means of variable infusions of Intralipid and heparin. A second muscle biopsy was taken from the same incision site at the end of the study. Carbohydrate oxidation significantly increased during the clamp (5.1±1.3 to 26.8±3.0 nmol/kg.min, P<0.01). However, despite the significant increase in pyruvate flux through pyruvate dehydrogenase, we did not observe any significant change in the acetyl-CoA-to-CoA ratio, suggesting that the contribution of β-oxidation-derived acetyl-CoA decreased during the clamp. The significant decrease in SCA concentration (5064±1776 to 2192±448 nmol/g dry wt., P<0.05), suggested that fatty acid oxidation was limited at a step preceding β-oxidation. This was confirmed by the observed decrease in LCA concentration during the clamp (855±270 to 377±83 nmol/g dry wt, P<0.05), in concert with the notion that high pyruvate flux blocks fatty acid entry into the mitochondria via inhibition of carnitine palmitoyltransferase I. (Supported by NIH grants DK-34817 and DK-46017 and Shriners Hospital grant 15849. ).",
author = "Sidossis, {L. S.} and Lopaschuk, {G. D.} and S. Klein and Wolfe, {R. R.}",
year = "1996",
language = "English (US)",
volume = "10",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "3",

}

TY - JOUR

T1 - Human skeletal muscle metabolism during hyperinsulinemic-hyperglycemia

AU - Sidossis, L. S.

AU - Lopaschuk, G. D.

AU - Klein, S.

AU - Wolfe, R. R.

PY - 1996

Y1 - 1996

N2 - Our goal was to examine changes in muscle acetyl-CoA, long-chain acylcarnitine (LCA), and short-chain acylcamitine (SCA) concentrations in response to hyrerinsulinemic-hyperglycemia. Seven healthy volunteers had a muscle biopsy taken from the lateral aspect of the vastus lateralis muscle approximately 15 cm above the patella, in the morning after they had fasted overnight (basal). Immediately following the basal period a hyperinsulinemic-hyperglycemic clamp (insulin=275 μU/mL, glucose=140 mg/dL) was started and continued for 5 h. Plasma FFA concentration was kept constant by means of variable infusions of Intralipid and heparin. A second muscle biopsy was taken from the same incision site at the end of the study. Carbohydrate oxidation significantly increased during the clamp (5.1±1.3 to 26.8±3.0 nmol/kg.min, P<0.01). However, despite the significant increase in pyruvate flux through pyruvate dehydrogenase, we did not observe any significant change in the acetyl-CoA-to-CoA ratio, suggesting that the contribution of β-oxidation-derived acetyl-CoA decreased during the clamp. The significant decrease in SCA concentration (5064±1776 to 2192±448 nmol/g dry wt., P<0.05), suggested that fatty acid oxidation was limited at a step preceding β-oxidation. This was confirmed by the observed decrease in LCA concentration during the clamp (855±270 to 377±83 nmol/g dry wt, P<0.05), in concert with the notion that high pyruvate flux blocks fatty acid entry into the mitochondria via inhibition of carnitine palmitoyltransferase I. (Supported by NIH grants DK-34817 and DK-46017 and Shriners Hospital grant 15849. ).

AB - Our goal was to examine changes in muscle acetyl-CoA, long-chain acylcarnitine (LCA), and short-chain acylcamitine (SCA) concentrations in response to hyrerinsulinemic-hyperglycemia. Seven healthy volunteers had a muscle biopsy taken from the lateral aspect of the vastus lateralis muscle approximately 15 cm above the patella, in the morning after they had fasted overnight (basal). Immediately following the basal period a hyperinsulinemic-hyperglycemic clamp (insulin=275 μU/mL, glucose=140 mg/dL) was started and continued for 5 h. Plasma FFA concentration was kept constant by means of variable infusions of Intralipid and heparin. A second muscle biopsy was taken from the same incision site at the end of the study. Carbohydrate oxidation significantly increased during the clamp (5.1±1.3 to 26.8±3.0 nmol/kg.min, P<0.01). However, despite the significant increase in pyruvate flux through pyruvate dehydrogenase, we did not observe any significant change in the acetyl-CoA-to-CoA ratio, suggesting that the contribution of β-oxidation-derived acetyl-CoA decreased during the clamp. The significant decrease in SCA concentration (5064±1776 to 2192±448 nmol/g dry wt., P<0.05), suggested that fatty acid oxidation was limited at a step preceding β-oxidation. This was confirmed by the observed decrease in LCA concentration during the clamp (855±270 to 377±83 nmol/g dry wt, P<0.05), in concert with the notion that high pyruvate flux blocks fatty acid entry into the mitochondria via inhibition of carnitine palmitoyltransferase I. (Supported by NIH grants DK-34817 and DK-46017 and Shriners Hospital grant 15849. ).

UR - http://www.scopus.com/inward/record.url?scp=33749143588&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749143588&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33749143588

VL - 10

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 3

ER -