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Titolo:
Prolonged elevation of plasma free fatty acids desensitizes the insulin secretory response to glucose in vivo in rats
Autore:
Mason, TM; Goh, T; Tchipashvili, V; Sandhu, H; Gupta, N; Lewis, GF; Giacca, A;
Indirizzi:
Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada Univ Toronto Toronto ON Canada M5S 1A8 ysiol, Toronto, ON M5S 1A8, Canada Univ Toronto, Dept Med, Toronto, ON M5S 1A8, Canada Univ Toronto Toronto ON Canada M5S 1A8 t Med, Toronto, ON M5S 1A8, Canada
Titolo Testata:
DIABETES
fascicolo: 3, volume: 48, anno: 1999,
pagine: 524 - 530
SICI:
0012-1797(199903)48:3<524:PEOPFF>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
PANCREATIC BETA-CELL; PYRUVATE-DEHYDROGENASE ACTIVITY; CHAIN ACYL-COA; MALONYL-COA; ISLETS; RELEASE; OBESITY; NIDDM; HYPERGLYCEMIA; PATHOGENESIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Giacca, A Univnadaonto, Dept Physiol, Med Sci Bldg,Room 3363, Toronto, ON M5S 1A8, Ca Univ Toronto Med Sci Bldg,Room 3363 Toronto ON Canada M5S 1A8 Ca
Citazione:
T.M. Mason et al., "Prolonged elevation of plasma free fatty acids desensitizes the insulin secretory response to glucose in vivo in rats", DIABETES, 48(3), 1999, pp. 524-530

Abstract

Prolonged exposure of pancreatic islets to free fatty acids (FFAs) inhibits glucose-stimulated insulin secretion (GSIS) in vitro. However, FFA inhibition of GSIS has not been clearly demonstrated in vivo. We examined the in vivo effect of prolonged elevation of plasma FFAs on GSIS using a two-step hyperglycemic clamp in rats treated with a 48-h intravenous infusion of either 20% Intralipid plus heparin (INT) (5 mu l/min plus heparin, 0.1 U/min; n = 8), oleate (OLE) (1.3 mu Eq/min; n = 6), saline (SAL) (n = 6), or bovine serum albumin (BSA) (vehicle for OLE; n = 5). Because there was no difference in any of the parameters between BSA and SAL rats, these groups were combined as control rats (CONT) (n = fl). At the end of the 48-h OLE/INT/CONT infusions, after an overnight fast, plasma glucose was clamped for 2 h at13 mmol/l and for another 2 h at 22 mmol/l. Preclamp plasma FFAs were elevated twofold (P < 0.01) versus CONT with both INT and OLE (NS, INT cs. OLE). Preclamp glucose, insulin, and C-peptide levels were higher in INT than in CONT rats (P < 0.05), suggesting insulin resistance, but they were not different in OLE and CONT rats. The insulin and C-peptide responses to the rise in plasma glucose from basal to 13 mmol/l were lower in OLE (336 +/- 72 pmol/l and 1.2 +/- 0.1 nmol/l, P < 0.01 and P < 0.05, respectively) than inCONT (552 +/- 54 and 1.9 +/- 0.1) rats, but they were not different between CONT and INT rats (648 +/- 150 and 2.0 +/- 0.4). The insulin and C-peptide responses to the rise in plasma glucose from 13 to 22 nmol/l n ere lower in both INT (1,188 +/- 204 pmol/l and 3.0 +/- 0.3 nmol/l, P < 0.01 and P < 0.001) and OLE (432 +/- 60 and 1.7 +/- 0.2, P < 0.001 vs. CONT or INT) ratsthan in CONT rats (1,662 +/- 174 and 5.0 +/- 0.6). In summary, 1) both INTand OLE decreased GSIS in vivo in rats, and 2) the impairing effect of INTon GSIS was less than that of OLE, which might be due to the different type of fatty acid (mostly polyunsaturated in INT versus monounsaturated as OLE) and/or to differential effects of INT and OLE on insulin sensitivity: Inconclusion, prolonged elevation of plasma FFAs can desensitize the insulinsecretory response to glucose in vivo, thus inducing a P-cell defect that is similar to that found in type 2 diabetes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 11:05:15