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 (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.Centro de Endocrinología Experimental y Aplicad

Assessment of the carcass traits of lambs with ¾ of the Texel breed genotype

Thirty six ¾ Texel (T) and 32 Ideal lambs were grown in feedlot for two months postweaning to evaluate final liveweight (FLW), relative average daily gain (ADGr) and various carcass characteristics, including: cold carcass weight (CCW), total lean weight (TLW), loin weight (LW), and total fat weight (TFW). Differences were found between males of the two genotypes in FW (P<.01) and TLW (P<.05); and between the females in TFW (P<.05). There were no differences between genotypes in ADGr. A multiple regression analysis relating FLW, as dependent variable, and the carcass variables as independent, showed that 73% of the variation in liveweight of the¾T animals was associated withLW and TLW. At conclusion of the confinement feeding, blood plasma samples from three lambs of each genotype/sex were analyzed for relative proportions of the mayor fatty acids and concentrations of total cholesterol and triglycerides. A negative relationship was found between the proportion of oleic acid and degree of fatness, expressed as (TFW/CCW) (100), whereas for linoleic acid the relationship was positive

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 (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.Centro de Endocrinología Experimental y Aplicad

Ontogénesis y evolución de la masa de células INGAP (Islet Neogenesis Associated Protein) positivas en el período intrauterino y en adultos con insulinorresistencia fisiológica (ratas preñadas)

Objetivos: Estudiar la cronología de aparición de células INGAP positivas en fetos de ratas normales y la evolución simultánea de su masa y la de las células β en ratas preñadas y su presencia en el páncreas de rata.Facultad de Ciencias Médica