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Titre du document / Document title

Paradoxical changes of muscle glutamine release during hyperinsulinemia euglycemia and hypoglycemia in humans: Further evidence for the glucose-glutamine cycle

Auteur(s) / Author(s)

MEYER Christian (1) ; WOERLE Hans J. ; GERICH John ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

(1) Carl T. Hayden VA Medical Center, Phoenix, AZ, ETATS-UNIS
University of Arizona College of Medicine, Tuscon, AZ, ETATS-UNIS
Department of Medicine, University of Rochester School of Medicine, Rochester, NY, ETATS-UNIS

Résumé / Abstract

Insulin suppresses and counterregulatory hormones increase proteolysis. Therefore, if proteolysis were a major factor determining amino acid fluxes in plasma, one would expect release of glutamine into plasma to be suppressed by insulin under euglycemic conditions and to be stimulated under hypoglycemic conditions. However, release of glutamine into plasma remains unaltered or increases during euglycemic hyperinsulinemia and decreases during insulin-induced hypoglycemia. To investigate the mechanisms for these paradoxical observations and the role of skeletal muscle, we infused overnight fasted volunteers with [U-14C] glutamine and measured release of glutamine into plasma, its removal from plasma, and forearm glutamine net balance, fractional extraction, uptake and release during 4-hour euglycemic (--5.0 mmol/L, n = 7) and hypoglycemic (∼3.1 mmol/L, n = 8) hyperinsulinemic (∼230 pmol/L) clamp experiments. During the euglycemic clamps, plasma glutamine uptake and release (both P <.05) and forearm muscle glutamine fractional extraction (P <.05), uptake (P < .02) and release (P <.01) all increased, whereas forearm glutamine net balance remained unchanged. The increase in muscle glutamine release (from 1.85 ± 0.26 to 2.18 ± 0.30 μmol . kg-1 . min-1) accounted for approximately 60% of the increase in total glutamine release into plasma (from 5.54 ± 0.47 to 6.10 ± 0.64 μmol . kg-1 . min-1) and correlated positively with the increase in muscle glucose uptake (r = 0.80, P <.03). During the hypoglycemic clamps, plasma glutamine uptake and release and forearm glutamine release remained unaltered, but forearm glutamine fractional extraction and uptake decreased approximately 25% (both P <.01) so that forearm glutamine net release increased from 0.37 ± 0.06 to 0.61 ± 0.09 μmol . kg-1. min-1 (P <.03). We conclude that skeletal muscle is largely responsible for the increased release of glutamine into plasma during euglycemic hyperinsulinemia in humans, and that this may be due to increased conversion of glucose to glutamine as part of the glucose-glutamine cycle; during hypoglycemic hyperinsulinemia decreased glutamine uptake by skeletal muscle may be important for providing substrate for increased glutamine gluconeogenesis.

Revue / Journal Title

Metabolism, clinical and experimental    ISSN  0026-0495 

Source / Source

2004, vol. 53, no9, pp. 1208-1214 [7 page(s) (article)] (40 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, New York, NY, ETATS-UNIS  (1952) (Revue)

Mots-clés anglais / English Keywords

Endocrinopathy

;

Pancreatic hormone

;

Gluconeogenesis

;

Substrate

;

Uptake

;

Forearm

;

Hypoglycemic agent

;

Blood plasma

;

Aminoacid

;

Proteolysis

;

Insulin

;

Glucose

;

Human

;

Induced hypoglycemia

;

Euglycemia

;

Release

;

Glutamine

;

Striated muscle

;

Hyperinsulinemia

;

Mots-clés français / French Keywords

Endocrinopathie

;

Hormone pancréatique

;

Glycémie normale

;

Gluconéogenèse

;

Substrat

;

Captation

;

Avant bras

;

Hypoglycémiant

;

Plasma sanguin

;

Aminoacide

;

Protéolyse

;

Insuline

;

Glucose

;

Homme

;

Hypoglycémie provoquée

;

Normoglycémie

;

Libération

;

Glutamine

;

Muscle strié

;

Hyperinsulinémie

;

Mots-clés espagnols / Spanish Keywords

Endocrinopatía

;

Hormona pancreática

;

Gluconeogénesis

;

Substrato

;

Captación

;

Antebrazo

;

Hipoglicemiante

;

Plasma sanguíneo

;

Aminoácido

;

Proteolisis

;

Insulina

;

Glucosa

;

Hombre

;

Hipoglicemia provocada

;

Normoglycemia

;

Liberación

;

Glutamina

;

Músculo estriado

;

Hiperinsulinemia

;

Localisation / Location

INIST-CNRS, Cote INIST : 6965, 35400012225034.0210

Nº notice refdoc (ud4) : 16115950



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