RESUMEN
To clarify the diversity in hypoglycemic actions of sulfonylureas, chronic effects of three sulfonylureas were compared on in vivo insulin-induced glucose uptake in peripheral tissues. After oral administration of glimepiride (CAS 93479-97-1), glibenclamide (CAS 10238-21-8), gliclazide (CAS 21187-98-4), or saline as control, two-step euglycemic clamp procedures were performed. During physiological hyperinsulinemia induced by 6 mU/kg/min insulin infusion, metabolic clearance rates (MCR) of glucose of the glimepiride-administered group (GP) significantly (p < 0.01) increased to 153% of the saline-administered group (SA). There was no significant statistical difference between the glibenclamide-administered group (GC), gliclazide-administered group (GZ) and SA. During 30 mU/kg/min clamps that lead to maximal insulin action, MCR of either GP or GC were significantly higher than those of SA (128% and 141%, p < 0.05 and p < 0.01, respectively). MCR of GZ were lower than those of GC (80%, p < 0.05), and showed no significant difference from those of SA. These data indicate that glimepiride activates insulin binding levels to a greater degree than the other two sulfonylureas, and that glibenclamide and glimepiride activate post-receptor binding mechanisms in peripheral tissues much more than gliclazide. These results suggest that hypoglycemic actions of sulfonylureas at the extra pancreatic levels vary with the nature of each reagent.
Asunto(s)
Hipoglucemiantes/farmacología , Compuestos de Sulfonilurea/farmacología , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Técnica de Clampeo de la Glucosa , Hiperinsulinismo/sangre , Insulina/sangre , Masculino , Ratas , Ratas WistarRESUMEN
The objective of this study was to determine by ultrasonographic measurements, an inexpensive and radiation-free technique, the association between bone health and lifestyle factors among a large population of Japanese women. Two hundred and fifty-six pre-menopausal women and 585 post-menopausal women who underwent a voluntary medical check-up for osteoporosis in 1996-1997 were analyzed. There were significant positive correlations between the bone density (designated as the stiffness value) vs the weight, the height and the body mass index of the subjects only in the post-menopausal group. Negative correlations were also found between the bone density vs the age and the years since menopause. Our data using ultrasonographic technique agree well with previous studies using other devices. In both groups, subjects with current or past exercise habits had higher stiffness values. Dietary habits had no effects on the stiffness value. Smoking habits had a trend towards negative effects and alcohol consumption seemed to have a trend towards positive effects on the stiffness value in post-menopausal women, but these effects did not reach statistical significance. Positive effects of current exercise on bone density were maintained after adjustment for past exercise habits. These results support the effectiveness of exercise begun in adulthood. Having a good exercise habit is one of the most effective ways of maintaining good bone health.
Asunto(s)
Densidad Ósea , Huesos/diagnóstico por imagen , Estilo de Vida , Adulto , Factores de Edad , Índice de Masa Corporal , Dieta , Ejercicio Físico , Femenino , Humanos , Japón , Persona de Mediana Edad , Osteoporosis/prevención & control , Posmenopausia , Premenopausia , Fumar , UltrasonografíaRESUMEN
We investigated the combined effects of estrogen deficiency and diabetes on bone mineral density (BMD) and bone metabolism in rats. Ten-week-old, female rats were randomly divided into four groups: controls (C), an ovariectomized group (O), a streptozotocin-induced diabetic group (S), and a combined ovariectomy and streptozotocin-induced diabetic group (OS). The BMD of the lumbar spine and the femur were measured before grouping and at 23 weeks old. At the end of the experiment, blood samples were obtained via cardiac puncture, and bone gla protein (BGP), tartrate-resistant acid phosphatase (TRAP) and 1,25-dihydroxyvitamin D levels were measured. The rats in the C, O, S, and OS groups, in that order, had higher levels of BMD of the lumbar spine and femur at 23 weeks of age. The BGP levels in the S and OS groups were significantly lower than in C and O groups. Significantly higher 1,25-dihydroxyvitamin D was observed in the O group compared with the C, S and OS groups. No differences were obtained in TRAP among four groups. Our data suggest that the combined effects of estrogen deficiency and diabetes on BMD are not synergistic or counteractive but additive.