Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Early insulin release effectively improves glucose tolerance: studies in two rodent models of type 2 diabetes mellitus
Autore:
de Souza, CJ; Gagen, K; Chen, W; Dragonas, N;
Indirizzi:
Novartis Inst Biomed Res, Summit, NJ 07901 USA Novartis Inst Biomed Res Summit NJ USA 07901 ed Res, Summit, NJ 07901 USA
Titolo Testata:
DIABETES OBESITY & METABOLISM
fascicolo: 2, volume: 3, anno: 2001,
pagine: 85 - 95
SICI:
1462-8902(200104)3:2<85:EIREIG>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
BETA-CELL DYSFUNCTION; POSTPRANDIAL HYPERGLYCEMIA; SECRETORY DYSFUNCTION; HEALTHY-SUBJECTS; NATURAL-HISTORY; FA/FA RATS; NIDDM; RESISTANCE; PATHOGENESIS; GLIPIZIDE;
Keywords:
A-4166; nateglinide; glipizide; insulin resistance; oral glucose load; OGTT; Zucker; high fat fed;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: de Souza, CJ Novartis Inst Biomed Res, 556 Morris Ave, Summit, NJ 07901 USA Novartis Inst Biomed Res 556 Morris Ave Summit NJ USA 07901 A
Citazione:
C.J. de Souza et al., "Early insulin release effectively improves glucose tolerance: studies in two rodent models of type 2 diabetes mellitus", DIABET OB M, 3(2), 2001, pp. 85-95

Abstract

Aim: Islet dysfunction, characterized by the loss of an acute insulin secretory response (AIR) to glucose is a well-established pathology of type 2 diabetes mellitus. Using oral insulin secreting agents with very different pharmacodynamic profiles, the present study was undertaken to test the hypothesis that, within the setting of an underlying insulin resistance, changesin the insulin response profile can differentially affect glycaemic control. Method: The mildly insulin resistant high-fat fed Sprague Dawley (HF) rat and the very insulin resistant Zucker fatty (fa/fa) rat, chronically fittedwith indwelling jugular cannula were subjected to an oral glucose load. Compounds were administered 5 min before the oral glucose load. Nateglinide (Nateg) was administered to elicit only an early insulin secretory response and glipizide (Glip) to elicit a later but greater insulin secretory response. Acetaminophen was used as a marker to assess for potential effects of these compounds on gastric emptying rates. Results: Nateg rapidly increased early insulin release (from -5 to 0) while the effects on total insulin release were similar to those in the controls and glucose excursions were eliminated in both diabetic models with no evidence of sustained hypoglycaemia. Conversely, Clip did not affect early insulin release but increased total insulin release (-15 to 120 min), but only after the oral glucose load. Clip partially curbed glucose excursions in the mildly insulin resistant HF rodent and was totally ineffective in the very insulin resistant Zucker rat. The differential effects could not be attributed to effects on gastric emptying rates. Conclusion: These data support the importance of early insulin release in type 2 diabetes mellitus and indicate that, independent of the level of insulin resistance, stimulating insulin release early and briefly provides formore effective and tighter glycaemic control than increasing insulin exposure to a greater magnitude later.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/01/20 alle ore 01:43:02