AJP - Endo Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab 283: E682-E691, 2002; doi:10.1152/ajpendo.00038.2002
0193-1849/02 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (62)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lam, T. K. T.
Right arrow Articles by Giacca, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lam, T. K. T.
Right arrow Articles by Giacca, A.
Vol. 283, Issue 4, E682-E691, October 2002

Free fatty acid-induced hepatic insulin resistance: a potential role for protein kinase C-delta

Tony K. T. Lam1, Hidenori Yoshii1, C. Andrew Haber1, Elena Bogdanovic1, Loretta Lam1, I. George Fantus1,2, and Adria Giacca1,2

Departments of 1 Physiology and 2 Medicine, University of Toronto, Toronto M5S 1A8, Canada

The mechanisms of the impairment in hepatic glucose metabolism induced by free fatty acids (FFAs) and the importance of FFA oxidation in these mechanisms remain unclear. FFA-induced peripheral insulin resistance has been linked to membrane translocation of novel protein kinase C (PKC) isoforms, but the role of PKC in hepatic insulin resistance has not been assessed. To investigate the biochemical pathways that are induced by FFA in the liver and their relation to glucose metabolism in vivo, we determined endogenous glucose production (EGP), the hepatic content of citrate (product of acetyl-CoA derived from FFA oxidation and oxaloacetate), and hepatic PKC isoform translocation after 2 and 7 h Intralipid + heparin (IH) or SAL in rats. Experiments were performed in the basal state and during hyperinsulinemic clamps (insulin infusion rate, 5 mU · kg-1 · min-1). IH increased EGP in the basal state (P < 0.001) and during hyperinsulinemia (P < 0.001) at 2 and 7 h. Also, 7-h infusion of IH induced resistance to the suppressive effect of insulin on EGP (P < 0.05). Glycerol infusion (resulting in plasma glycerol levels similar to IH infusion) did not have any effect on EGP. IH increased hepatic citrate content by twofold, independent of the insulin levels and the duration of IH infusion. IH induced hepatic PKC-delta translocation from the cytosolic to membrane fraction in all groups. PKC-delta translocation was greater at 7 compared with 2 h (P < 0.05). In conclusion, 1) increased FFA oxidation may contribute to the FFA-induced increase in EGP in the basal state and during hyperinsulinemia but is not associated with FFA-induced hepatic insulin resistance, and 2) the progressive insulin resistance induced by FFA in the liver is associated with a progressive increase in hepatic PKC-delta translocation.

hepatic glucose production; free fatty acid oxidation; hyperinsulinemic-euglycemic clamp


This article has been cited by other articles:


Home page
 DiabetesHome page
R. Ross, P. Y.T. Wang, M. Chari, C. K.L. Lam, L. Caspi, H. Ono, E. D. Muse, X. Li, R. Gutierrez-Juarez, P. E. Light, et al.
Hypothalamic Protein Kinase C Regulates Glucose Production
Diabetes, August 1, 2008; 57(8): 2061 - 2065.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
J.-a Kim, Y. Wei, and J. R. Sowers
Role of Mitochondrial Dysfunction in Insulin Resistance
Circ. Res., February 29, 2008; 102(4): 401 - 414.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
E. Park, V. Wong, X. Guan, A. I Oprescu, and A. Giacca
Salicylate prevents hepatic insulin resistance caused by short-term elevation of free fatty acids in vivo
J. Endocrinol., November 1, 2007; 195(2): 323 - 331.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H.-Y. Liu, Q. F. Collins, Y. Xiong, F. Moukdar, E. G. Lupo Jr., Z. Liu, and W. Cao
Prolonged Treatment of Primary Hepatocytes with Oleate Induces Insulin Resistance through p38 Mitogen-activated Protein Kinase
J. Biol. Chem., May 11, 2007; 282(19): 14205 - 14212.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
C. D. Champagne, D. S. Houser, and D. E. Crocker
Glucose metabolism during lactation in a fasting animal, the northern elephant seal
Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2006; 291(4): R1129 - R1137.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
C. Everett-Grueter, D. S. Edgerton, E. P. Donahue, S. Vaughan, C. A. Chu, D. K. Sindelar, and A. D. Cherrington
The effect of an acute elevation of NEFA concentrations on glucagon-stimulated hepatic glucose output
Am J Physiol Endocrinol Metab, September 1, 2006; 291(3): E449 - E459.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
A. M. Hennige, N. Stefan, K. Kapp, R. Lehmann, C. Weigert, A. Beck, K. Moeschel, J. Mushack, E. Schleicher, and H.-U. Haring
Leptin down-regulates insulin action through phosphorylation of serine-318 in insulin receptor substrate 1
FASEB J, June 1, 2006; 20(8): 1206 - 1208.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
H. Yoshii, T. K. T. Lam, N. Gupta, T. Goh, C. A. Haber, H. Uchino, T. T. Y. Kim, V. Z. Chong, K. Shah, I. G. Fantus, et al.
Effects of portal free fatty acid elevation on insulin clearance and hepatic glucose flux
Am J Physiol Endocrinol Metab, June 1, 2006; 290(6): E1089 - E1097.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
A. Aziz, G. H. Anderson, A. Giacca, and F. Cho
Hyperglycemia after protein ingestion concurrent with injection of a GLP-1 receptor agonist in rats: a possible role for dietary peptides
Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2005; 289(3): R688 - R694.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
M. Trivedi and M. F. Lokhandwala
Rosiglitazone restores renal D1A receptor-Gs protein coupling by reducing receptor hyperphosphorylation in obese rats
Am J Physiol Renal Physiol, August 1, 2005; 289(2): F298 - F304.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
A. Charbonneau, A. Melancon, C. Lavoie, and J.-M. Lavoie
Alterations in hepatic glucagon receptor density and in Gs{alpha} and Gi{alpha}2 protein content with diet-induced hepatic steatosis: effects of acute exercise
Am J Physiol Endocrinol Metab, July 1, 2005; 289(1): E8 - E14.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
L. M. Watts, V. P. Manchem, T. A. Leedom, A. L. Rivard, R. A. McKay, D. Bao, T. Neroladakis, B. P. Monia, D. M. Bodenmiller, J. X.-C. Cao, et al.
Reduction of Hepatic and Adipose Tissue Glucocorticoid Receptor Expression With Antisense Oligonucleotides Improves Hyperglycemia and Hyperlipidemia in Diabetic Rodents Without Causing Systemic Glucocorticoid Antagonism
Diabetes, June 1, 2005; 54(6): 1846 - 1853.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
L. Puljak, M. J Pagliassotti, Y. Wei, I. Qadri, V. Parameswara, V. Esser, J. G. Fitz, and G. Kilic
Inhibition of cellular responses to insulin in a rat liver cell line. A role for PKC in insulin resistance
J. Physiol., March 1, 2005; 563(2): 471 - 482.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
M. E. Cleasby, N. Dzamko, B. D. Hegarty, G. J. Cooney, E. W. Kraegen, and J.-M. Ye
Metformin Prevents the Development of Acute Lipid-Induced Insulin Resistance in the Rat Through Altered Hepatic Signaling Mechanisms
Diabetes, December 1, 2004; 53(12): 3258 - 3266.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
Y. Wei and M. J. Pagliassotti
Hepatospecific effects of fructose on c-jun NH2-terminal kinase: implications for hepatic insulin resistance
Am J Physiol Endocrinol Metab, November 1, 2004; 287(5): E926 - E933.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
V. T. Samuel, Z.-X. Liu, X. Qu, B. D. Elder, S. Bilz, D. Befroy, A. J. Romanelli, and G. I. Shulman
Mechanism of Hepatic Insulin Resistance in Non-alcoholic Fatty Liver Disease
J. Biol. Chem., July 30, 2004; 279(31): 32345 - 32353.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
M. Muurling, A. M. van den Hoek, R. P. Mensink, H. Pijl, J. A. Romijn, L. M. Havekes, and P. J. Voshol
Overexpression of APOC1 in obob mice leads to hepatic steatosis and severe hepatic insulin resistance
J. Lipid Res., January 1, 2004; 45(1): 9 - 16.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
H. Kim, M. Haluzik, Z. Asghar, D. Yau, J. W. Joseph, A. M. Fernandez, M. L. Reitman, S. Yakar, B. Stannard, L. Heron-Milhavet, et al.
Peroxisome Proliferator-Activated Receptor-{alpha} Agonist Treatment in a Transgenic Model of Type 2 Diabetes Reverses the Lipotoxic State and Improves Glucose Homeostasis
Diabetes, July 1, 2003; 52(7): 1770 - 1778.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
T. K. T. Lam, A. Carpentier, G. F. Lewis, G. van de Werve, I. G. Fantus, and A. Giacca
Mechanisms of the free fatty acid-induced increase in hepatic glucose production
Am J Physiol Endocrinol Metab, May 1, 2003; 284(5): E863 - E873.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
T. K. T. Lam, G. Van de Werve, and A. Giacca
Free fatty acids increase basal hepatic glucose production and induce hepatic insulin resistance at different sites
Am J Physiol Endocrinol Metab, February 1, 2003; 284(2): E281 - E290.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online