Islet adaptive changes to fructose-induced insulin resistance: β-cell mass, glucokinase, glucose metabolism, and insulin secretion

β-Cell mass, hexokinase/glucokinase (HK/GK) activity, glucose metabolism and insulin secretion were studied in the islets of rats with fructose-induced insulin resistance (IR). Normal male Wistar rats were fed a standard commercial diet and water without (control, C) or with 10% fructose-rich diet (...

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Autores principales: Maiztegui, Bárbara, Borelli, María Inés, Raschia, M. A., Del Zotto, Héctor Herminio, Gagliardino, Juan José
Formato: Articulo
Lenguaje:Inglés
Publicado: 2009
Materias:
Ciencias Médicas
insulin
glucose
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/82723
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-82723
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
insulin
glucose
spellingShingle Ciencias Médicas
insulin
glucose
Maiztegui, Bárbara
Borelli, María Inés
Raschia, M. A.
Del Zotto, Héctor Herminio
Gagliardino, Juan José
Islet adaptive changes to fructose-induced insulin resistance: β-cell mass, glucokinase, glucose metabolism, and insulin secretion
topic_facet Ciencias Médicas
insulin
glucose
description β-Cell mass, hexokinase/glucokinase (HK/GK) activity, glucose metabolism and insulin secretion were studied in the islets of rats with fructose-induced insulin resistance (IR). Normal male Wistar rats were fed a standard commercial diet and water without (control, C) or with 10% fructose-rich diet (FRD) for 3 weeks. Blood glucose (strips), triglyceride (commercial kit), and insulin (RIA) levels were measured at the time of death. Glucose-induced insulin release, glucose metabolism (14CO2 and 3H2O production from D-[U-14C]- and D-[5-3H]-glucose) and HK/GK activity (G-6-P production), transcription (RTPCR), protein expression (Western blot), and cellular compartmentalization were measured in isolated islets (collagenase digestion). FRD rats presented normoglycemia but impaired glucose tolerance, hypertriglyceridemia, hyperinsulinemia, and increased HOMA-IR index. In these rats, β-cell mass decreased significantly by 33%, with a 44% increase in the percentage of apoptotic cells. Glucose-induced insulin release and islet glucose metabolism were higher in FRD rats. While GK activity (total and cytosolic fraction) and protein expression were significantly higher in FRD islets, HK showed no change in any of these parameters. Our results demonstrate that the changes induced by dietary-induced IR upon β-cell function and mass are strongly conditional on the nutrient model used. In our model (intact animals with impaired glucose tolerance), GK activity increases through mechanisms previously shown only in vitro or under highly hyperglycemic conditions. Such an increase plays a pivotal role in the adaptive increased release of insulin in response to IR, even in the presence of marked β-cell mass reduction.
format Articulo
Articulo
author Maiztegui, Bárbara
Borelli, María Inés
Raschia, M. A.
Del Zotto, Héctor Herminio
Gagliardino, Juan José
author_facet Maiztegui, Bárbara
Borelli, María Inés
Raschia, M. A.
Del Zotto, Héctor Herminio
Gagliardino, Juan José
author_sort Maiztegui, Bárbara
title Islet adaptive changes to fructose-induced insulin resistance: β-cell mass, glucokinase, glucose metabolism, and insulin secretion
title_short Islet adaptive changes to fructose-induced insulin resistance: β-cell mass, glucokinase, glucose metabolism, and insulin secretion
title_full Islet adaptive changes to fructose-induced insulin resistance: β-cell mass, glucokinase, glucose metabolism, and insulin secretion
title_fullStr Islet adaptive changes to fructose-induced insulin resistance: β-cell mass, glucokinase, glucose metabolism, and insulin secretion
title_full_unstemmed Islet adaptive changes to fructose-induced insulin resistance: β-cell mass, glucokinase, glucose metabolism, and insulin secretion
title_sort islet adaptive changes to fructose-induced insulin resistance: β-cell mass, glucokinase, glucose metabolism, and insulin secretion
publishDate 2009
url http://sedici.unlp.edu.ar/handle/10915/82723
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