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Titolo:
Prolonged elevation of plasma free fatty acids impairs pancreatic beta-cell function in obese nondiabetic humans but not in individuals with type 2 diabetes
Autore:
Carpentier, A; Mittelman, SD; Bergman, RN; Giacca, A; Lewis, GF;
Indirizzi:
Univ Toronto, Dept Med, Toronto, ON, Canada Univ Toronto Toronto ON Canada iv Toronto, Dept Med, Toronto, ON, Canada Univ Toronto, Dept Physiol, Toronto, ON, Canada Univ Toronto Toronto ON Canada oronto, Dept Physiol, Toronto, ON, Canada Univ So Calif, Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA Univ So Calif Los Angeles CA USA 90033 Biophys, Los Angeles, CA 90033 USA
Titolo Testata:
DIABETES
fascicolo: 3, volume: 49, anno: 2000,
pagine: 399 - 408
SICI:
0012-1797(200003)49:3<399:PEOPFF>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
STIMULATED INSULIN-SECRETION; PYRUVATE-DEHYDROGENASE ACTIVITY; ISOLATED RAT HEPATOCYTES; LONG-TERM EXPOSURE; GLUCOSE-METABOLISM; PATHOGENESIS; NIDDM; CLEARANCE; ISLETS; MECHANISMS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Lewis, GF Univ Toronto, Toronto Gen Hosp, Dept Med, Div Endocrinol, 200 Elizabeth St,Room EN 11-229, Toronto, ON M5G 2C4, Canada Univ Toronto 200 Elizabeth St,Room EN 11-229 Toronto ON Canada M5G 2C4
Citazione:
A. Carpentier et al., "Prolonged elevation of plasma free fatty acids impairs pancreatic beta-cell function in obese nondiabetic humans but not in individuals with type 2 diabetes", DIABETES, 49(3), 2000, pp. 399-408

Abstract

Our recent in vivo observations in healthy nonobese humans have demonstrated that prolonged elevation of plasma free fatty acids (FFAs) results in diminished glucose-stimulated insulin secretion (GSIS) when the FFA-mediated decrease in insulin sensitivity is taken into account. In the present study, we investigated whether obese individuals and patients with type 2 diabetes are more sensitive than healthy control subjects to the inhibitory effect of prolonged elevation of plasma FFAs on GSIS, In seven patients with type 2 diabetes and seven healthy nondiabetic obese individuals, we assessed GSIS with a programmed graded intravenous glucose infusion on two occasions,6-8 weeks apart, with and without a prior 48-h infusion of heparin and Intralipid, which was designed to raise plasma FFA concentration approximatelytwofold over basal, The nondiabetic obese subjects had a significant 21% decrease in GSIS (P = 0.0008) with the heparin and Intralipid infusion, associated with a decrease in whole body insulin clearance. The impairment in GSIS was evident at low (<11 mmol/l) but not at higher plasma glucose concentrations. In contrast, the patients with type 2 diabetes had a slight increase in GSIS CP = 0.027) and no change in insulin clearance, although there was marked interindividual variability in response. Plasma proinsulin concentrations measured in a subset of subjects were not altered in either groupby the infusion of heparin and Intralipid. In summary, 1) obese nondiabetic individuals are susceptible to a desensitization of GSIS with heparin andIntralipid infusion, and 2) patients with type 2 diabetes do not demonstrate such susceptibility when FFAs are elevated approximately twofold above basal with heparin and Intralipid, Our results suggest that FFAs could play an important role in the development of beta-cell failure in obese individuals who are at risk for developing type 2 diabetes. They do not, however, seem to further deteriorate the beta-cell function of patients who already have established type 2 diabetes and may even result in a slight increase inGSIS in this latter group.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 01:58:07