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Titolo:
Effects of adenovirus-mediated liver-selective overexpression of protein tyrosine phosphatase-1b on insulin sensitivity in vivo
Autore:
Wang, J; Cheung, AT; Kolls, JK; Starks, WW; Martinez-Hernandez, A; Dietzen, D; Bryer-Ash, M;
Indirizzi:
Univ Tennessee, Memphis, TN USA Univ Tennessee Memphis TN USAUniv Tennessee, Memphis, TN USA Vet Adm Med Ctr, Res Serv, Memphis, TN 38104 USA Vet Adm Med Ctr Memphis TN USA 38104 Ctr, Res Serv, Memphis, TN 38104 USA Louisiana State Univ, New Orleans, LA USA Louisiana State Univ New Orleans LA USA State Univ, New Orleans, LA USA Vet Adm Med Ctr, Dept Pathol, Memphis, TN 38104 USA Vet Adm Med Ctr Memphis TN USA 38104 , Dept Pathol, Memphis, TN 38104 USA
Titolo Testata:
DIABETES OBESITY & METABOLISM
fascicolo: 5, volume: 3, anno: 2001,
pagine: 367 - 380
SICI:
1462-8902(200110)3:5<367:EOALOO>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEPENDENT DIABETES-MELLITUS; GROWTH-FACTOR RECEPTORS; HUMAN SKELETAL-MUSCLE; ADIPOSE-TISSUE; HUMAN-PLACENTA; PHOSPHOTYROSINE PHOSPHATASE; OBESE SUBJECTS; IN-VIVO; INCREASED ABUNDANCE; GLUCOSE-TOLERANCE;
Keywords:
glucose clamp; liver; skeletal muscle; fat; insulin signalling;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
67
Recensione:
Indirizzi per estratti:
Indirizzo: Bryer-Ash, M Univ Calif Los Angeles, Dept Endocrinol, Div Endocrinol, 900 Vet Ave,Suite24-130, Los Angeles, CA 90095 USA Univ Calif Los Angeles 900 Vet Ave,Suite 24-130 Los Angeles CA USA 90095
Citazione:
J. Wang et al., "Effects of adenovirus-mediated liver-selective overexpression of protein tyrosine phosphatase-1b on insulin sensitivity in vivo", DIABET OB M, 3(5), 2001, pp. 367-380

Abstract

Aim: Protein tyrosine phosphatase-1B (PTP-1B) is an intracellular PTP known to dephosphorylate and inactivate upstream tyrosine phosphoproteins in the insulin signalling cascade. We and others reported increased abundance ofcatalytically impaired PTP-1B in tissue lysates from obese human subjects with and without type 2 diabetes, while genetic knockout of PTP-1B improvesinsulin sensitivity and prevents nutritionally mediated insulin resistanceand obesity. The aim of the present work was to further elucidate the roleof PTP-1B in glucose metabolism in vivo. Methods: We used adenoviral constructs incorporating cDNAs for either wild-type (W/T) or a catalytically inactive (CS)-S-215 (C/S) mutant PTP-1B to achieve liver-selective PTP-1B overexpression in young Sprague-Dawley rats using tail vein injection, based on the high degree of hepatotropism of adenovirus 5 (Ad5). An Ad5-lacZ construct encoding beta -galactosidase was usedas a control for viral effects alone. A hyperinsulinaemic euglycaemic clamp was used to study whole body glucose disposal and endogenous glucose production rates. Results: Control studies in HIRcB cells confirmed catalytic activity and inactivity of W/T and C/S respectively. Mean PTP-1B abundance was 2.24 +/-0.02- and 2.33 +/- 0.04-fold of saline-treated control in liver lysates of W/T and C/S rats respectively. Liver selective overexpression was confirmed by analysis of tissue lysates from liver, fat and muscle tissues. Ad5 treatment did not result in a statistically or clinically significant liver injury, as determined by serum alanine aminotransferase and histological examination. Seven days post injection, no significant difference in rate of weight gain, fasting blood glucose or insulin levels were seen in any group. Similarly, under steady-state glucose clamp conditions, glucose disposal rate (R-d), endogenous glucose production rate (EGP) and serum insulin levels were similar in all groups. Conclusion: We conclude that moderate medium-term overabundance, to a degree resembling that seen in insulin-resistant states, of PTP-1B in liver tissue does not alter insulin action on glucose metabolism and that the major site of action of PTP-1B is presumably at insulin-responsive target tissue or tissues other than the liver.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/10/20 alle ore 20:50:14