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Titolo:
Physiological hyperinsulinemia impairs insulin-stimulated glycogen synthase activity and glycogen synthesis
Autore:
Iozzo, P; Pratipanawatr, T; Pijl, H; Vogt, C; Kumar, V; Pipek, R; Matsuda, M; Mandarino, LJ; Cusi, KJ; DeFronzo, RA;
Indirizzi:
Univ Texas, Hlth Sci Ctr, Dept Med, Diabet Div, San Antonio, TX 78284 USA Univ Texas San Antonio TX USA 78284 Diabet Div, San Antonio, TX 78284 USA Univ Texas, Hlth Sci Ctr, Dept Biochem, Diabet Div, San Antonio, TX 78284 USA Univ Texas San Antonio TX USA 78284 Diabet Div, San Antonio, TX 78284 USA
Titolo Testata:
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
fascicolo: 5, volume: 280, anno: 2001,
pagine: E712 - E719
SICI:
0193-1849(200105)280:5<E712:PHIIGS>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEPENDENT DIABETES-MELLITUS; HUMAN SKELETAL-MUSCLE; II MESSENGER-RNA; GLUCOSE-TRANSPORT; TYROSINE PHOSPHORYLATION; C-CBL; RECEPTOR SUBSTRATE-1; INDIRECT CALORIMETRY; 3T3-L1 ADIPOCYTES; TRANSGENIC MICE;
Keywords:
hexokinase II; glucose transporter 4; skeletal muscle; insulin resistance;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: DeFronzo, RA Univ Texas, Hlth Sci Ctr, Dept Med, Diabet Div, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA Univ Texas 7703 Floyd Curl Dr San Antonio TX USA 78284 84 USA
Citazione:
P. Iozzo et al., "Physiological hyperinsulinemia impairs insulin-stimulated glycogen synthase activity and glycogen synthesis", AM J P-ENDO, 280(5), 2001, pp. E712-E719

Abstract

Although chronic hyperinsulinemia has been shown to induce insulin resistance, the basic cellular mechanisms responsible for this phenomenon are unknown. The present study was performed 1) to determine the time-related effect of physiological hyperinsulinemia on glycogen synthase (GS) activity, hexokinase II (HKII) activity and mRNA content, and GLUT-4 protein in muscle from healthy subjects, and 2) to relate hyperinsulinemia-induced alterationsin these parameters to changes in glucose metabolism in vivo. Twenty healthy subjects had a 240-min euglycemic insulin clamp study with muscle biopsies and then received a low-dose insulin infusion for 24 (n = 6) or 72 h (n = 14) (plasma insulin concentration = 121 +/- 9 or 143 +/- 25 pmol/l, respectively). During the baseline insulin clamp, GS fractional velocity (0.075 /- 0.008 to 0.229 +/- 0.02, P < 0.01), HKII mRNA content (0.179 +/- 0.034 to 0.354 +/- 0.087, P < 0.05), and HKII activity (2.41 +/- 0.63 to 3.35 +/-0.54 pmol . min(-1) . ng(-1), P < 0.05), as well as whole body glucose disposal and nonoxidative glucose disposal, increased. During the insulin clamp performed after 24 and 72 h of sustained physiological hyperinsulinemia, the ability of insulin to increase muscle GS fractional velocity, total body glucose disposal, and nonoxidative glucose disposal was impaired tall P <0.01), whereas the effect of insulin on muscle HKII mRNA, HKII activity, GLUT-4 protein content, and whole body rates of glucose oxidation and glycolysis remained unchanged. Muscle glycogen concentration did not change [116 /- 28 vs. 126 +/- 29 mu mol/kg muscle, P = nonsignificant (NS)1 and was not correlated with the change in nonoxidative glucose disposal (r = 0.074, P= NS). In summary, modest chronic hyperinsulinemia may contribute directly(independent of change in muscle glycogen concentration) to the development of insulin resistance by its impact on the GS pathway.

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Documento generato il 05/04/20 alle ore 03:54:33