Flux control in the rat gastrocnemius glycogen synthesis pathway by in vivo 13C/31P NMR spectroscopy

被引:21
作者
Chase, JR
Rothman, DL
Shulman, RG
机构
[1] Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06510 USA
[2] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 2001年 / 280卷 / 04期
关键词
metabolic control analysis; glucose transport; hyperglycemia; hyperinsulinemia;
D O I
10.1152/ajpendo.2001.280.4.E598
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
To determine the relative contributions of glucose transport/hexokinase, glycogen synthase (GSase), and glycolysis to the control of insulin-stimulated muscle glycogen synthesis, we combined C-13 and P-31 NMR to quantitate the glycogen synthesis rate and glucose 6-phosphate (G-6-P) levels in rat (Sprague-Dawley) gastrocnemius muscle during hyperinsulinemia at euglycemic (E) and hyperglycemic (H) glucose concentrations under thiopental anesthesia. Flux control was calculated using metabolic control analysis. The combined control coefficient of glucose transport/hexokinase (GT/Hk) for glycogen synthesis was 1.1 +/- 0.03 (direct measure) and 1.14-1.16 (calculated for a range of glycolytic fluxes), whereas the control coefficient for GSase was much lower (0.011-0.448). We also observed that the increase in in vivo [G-6-P] from E to H (0.22 +/- 0.03 to 0.40 +/- 0.03 mM) effects a supralinear increase in the in vitro velocity of GSase, from 14.6 to 26.1 mU.kg(-1).min-1 (1.8-fold). All measurements suggest that the majority of the flux control of muscle glycogen synthesis is at the GT/Hk step.
引用
收藏
页码:E598 / E607
页数:10
相关论文
共 40 条
[1]   IN-VIVO P-31 NMR MEASUREMENT OF GLUCOSE-6-PHOSPHATE IN THE RAT MUSCLE AFTER EXERCISE [J].
BLOCH, G ;
CHASE, JR ;
AVISON, MJ ;
SHULMAN, RG .
MAGNETIC RESONANCE IN MEDICINE, 1993, 30 (03) :347-350
[2]   IN-VIVO REGULATION OF RAT MUSCLE GLYCOGEN RESYNTHESIS AFTER INTENSE EXERCISE [J].
BLOCH, G ;
CHASE, JR ;
MEYER, DB ;
AVISON, MJ ;
SHULMAN, GI ;
SHULMAN, RG .
AMERICAN JOURNAL OF PHYSIOLOGY, 1994, 266 (01) :E85-E91
[3]   CORRELATION BETWEEN MUSCLE GLYCOGEN-SYNTHASE ACTIVITY AND INVIVO INSULIN ACTION IN MAN [J].
BOGARDUS, C ;
LILLIOJA, S ;
STONE, K ;
MOTT, D .
JOURNAL OF CLINICAL INVESTIGATION, 1984, 73 (04) :1185-1190
[4]   GLUCOSE-TRANSPORT IN HUMAN SKELETAL-MUSCLE - THE INVIVO RESPONSE TO INSULIN [J].
BONADONNA, RC ;
SACCOMANI, MP ;
SEELY, L ;
ZYCH, KS ;
FERRANNINI, E ;
COBELLI, C ;
DEFRONZO, RA .
DIABETES, 1993, 42 (01) :191-198
[5]   Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes [J].
Cline, GW ;
Petersen, KF ;
Krssak, M ;
Shen, J ;
Hundal, RS ;
Trajanoski, Z ;
Inzucchi, S ;
Dresner, A ;
Rothman, DL ;
Shulman, GI .
NEW ENGLAND JOURNAL OF MEDICINE, 1999, 341 (04) :240-246
[6]   A COMPARTMENTAL MODEL TO QUANTITATE INVIVO GLUCOSE-TRANSPORT IN THE HUMAN FOREARM [J].
COBELLI, C ;
SACCOMANI, MP ;
FERRANNINI, E ;
DEFRONZO, RA ;
GELFAND, R ;
BONADONNA, R .
AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 257 (06) :E943-E958
[7]   INFLUENCE OF EPINEPHRINE + INSULIN ON URIDINE DIPHOSPHATE GLUCOSE-ALPHA-GLUCAN TRANSFERASE + PHOSPHORYLASE IN MUSCLE [J].
CRAIG, JW ;
LARNER, J .
NATURE, 1964, 202 (493) :971-&
[8]  
DANFORTH WH, 1965, J BIOL CHEM, V240, P588
[9]   EXPRESSION OF HUMAN GLUT4 IN MICE RESULTS IN INCREASED INSULIN ACTION [J].
DEEMS, RO ;
EVANS, JL ;
DEACON, RW ;
HONER, CM ;
CHU, DT ;
BURKI, K ;
FILLERS, WS ;
COHEN, DK ;
YOUNG, DA .
DIABETOLOGIA, 1994, 37 (11) :1097-1104
[10]   Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity [J].
Dresner, A ;
Laurent, D ;
Marcucci, M ;
Griffin, ME ;
Dufour, S ;
Cline, GW ;
Slezak, LA ;
Andersen, DK ;
Hundal, RS ;
Rothman, DL ;
Petersen, KF ;
Shulman, GI .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (02) :253-259