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1.
Am J Physiol Regul Integr Comp Physiol ; 289(4): R1064-73, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15961530

RESUMEN

We evaluated the effect of chronic (3 wk) subcutaneous treatment with progesterone and estradiol (PE; producing serum levels observed in the 3rd trimester of pregnancy) or placebo (C) on hepatic and whole body insulin sensitivity and response to hypoglycemia in conscious, overnight-fasted nonpregnant female dogs, using tracer and arteriovenous difference techniques. Insulin was infused peripherally for 3 h at 1.8 mU x kg(-1) x min(-1). Glucose was allowed to fall to 3 mM (Hypo) or maintained at 6 mM (Eugly) by peripheral glucose infusion. Insulin concentrations were significantly higher in Eugly-PE (n = 7) and Hypo-PE (n = 7) than in Eugly-C (n = 6) and Hypo-C groups (n = 7), but there were no significant differences in hepatic insulin extraction. Concentrations of glucagon, cortisol, epinephrine, and norepinephrine did not differ significantly between Eugly groups or between Hypo groups. Whole body glucose disposal, adjusted for the differences in insulin between groups, was 35% higher in Eugly-C vs. Eugly-PE groups (P < 0.05). Eugly-C and Eugly-PE groups exhibited similar rates of net hepatic glucose uptake, but the rate of glucose appearance was greater in Eugly-PE in the last hour (P < 0.05). Net hepatic glucose output was greater (P < 0.05) in Hypo-PE than in Hypo-C groups, and the glucose infusion rate required to maintain equivalent hypoglycemia was less (P < 0.05). The rate of gluconeogenic flux did not differ between Hypo groups. Chronic progesterone and estradiol exposure caused whole body (primarily skeletal muscle) insulin resistance and enhanced the liver's response to hypoglycemia without altering counterregulatory hormone concentrations.


Asunto(s)
Estradiol/administración & dosificación , Glucosa/metabolismo , Hipoglucemia/metabolismo , Resistencia a la Insulina , Insulina/administración & dosificación , Hígado/metabolismo , Progesterona/administración & dosificación , Animales , Perros , Hígado/efectos de los fármacos , Tasa de Depuración Metabólica , Sensibilidad y Especificidad , Factores de Tiempo , Mujeres
2.
Am J Transplant ; 5(10): 2368-77, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16162184

RESUMEN

The present studies were designed to determine if totally pancreatectomized dogs that underwent islet auto-transplantation retained a functional pancreatic counterregulatory response to mild non-insulin-induced hypoglycemia. Six dogs underwent total pancreatectomy followed by islet auto-transplantation to spleen or omentum. The animals recovered and fasting plasma glucose and insulin levels were normal. Each study consisted of a 40-min control and 2-h test period. At the onset of the test period, a glycogen phosphorylase inhibitor was administered to create mild hypoglycemia. Plasma glucose in the transplanted dogs fell from 120 +/- 4 to 80 +/- 3 mg/dL, similar to the minimum in control dogs without islet auto-transplantation (108 +/- 2 to 84 +/- 5 mg/dL). The fall in plasma insulin was similar in both groups. Glucagon, however, rose in response to hypoglycemia in the control dogs (Delta24 +/- 7 pg/mL; p < 0.05), but failed to rise significantly in the transplanted dogs (Delta9 +/- 6 pg/mL). In fact, only 1 of 7 control dogs failed to increase plasma glucagon by at least 25%, whereas 4 of 6 transplanted dogs failed to do so. In conclusion, in conscious dogs with successfully auto-transplanted islets, the beta cell response to mild non-insulin-induced hypoglycemia was normal, whereas the alpha cell response was not.


Asunto(s)
Células Secretoras de Glucagón/metabolismo , Células Secretoras de Glucagón/fisiología , Hipoglucemia/patología , Células Secretoras de Insulina/citología , Insulina/metabolismo , Trasplante de Islotes Pancreáticos/métodos , Islotes Pancreáticos/citología , Bazo/citología , Trasplante Autólogo/métodos , Animales , Área Bajo la Curva , Arginina/química , Glucemia/metabolismo , Supervivencia Celular , Trasplante de Células , Perros , Femenino , Glucagón/metabolismo , Glucógeno Fosforilasa/antagonistas & inhibidores , Supervivencia de Injerto , Insulina/sangre , Insulina/farmacología , Masculino , Páncreas/patología , Páncreas/fisiología , Bazo/patología , Factores de Tiempo
3.
Am J Physiol Endocrinol Metab ; 284(5): E1027-36, 2003 May.
Artículo en Inglés | MEDLINE | ID: mdl-12569088

RESUMEN

Arteriovenous difference and tracer ([3-(3)H]glucose) techniques were used in 42-h-fasted conscious dogs to identify any insulin-like effects of intraportally administered glucagon-like peptide 1-(7-36)amide (GLP-1). Each study consisted of an equilibration, a basal, and three 90-min test periods (P1, P2, and P3) during which somatostatin, intraportal insulin (3-fold basal) and glucagon (basal), and peripheral glucose were infused. Saline was infused intraportally in P1. During P2 and P3, GLP-1 was infused intraportally at 0.9 and 5.1 pmol. kg(-1). min(-1) in eight dogs, at 10 and 20 pmol. kg(-1). min(-1) in seven dogs, and at 0 pmol. kg(-1). min(-1) in eight dogs (control group). Net hepatic glucose uptake was significantly enhanced during GLP-1 infusion at 20 pmol. kg(-1). min(-1) [21.8 vs. 13.4 micromol. kg(-1). min(-1) (control), P < 0.05]. Glucose utilization was significantly increased during infusion at 10 and 20 pmol. kg(-1). min(-1) [87.3 +/- 8.3 and 105.3 +/- 12.8, respectively, vs. 62.2 +/- 5.3 and 74.7 +/- 7.4 micromol. kg(-1). min(-1) (control), P < 0.05]. The glucose infusion rate required to maintain hyperglycemia was increased (P < 0.05) during infusion of GLP-1 at 5.1, 10, and 20 pmol. kg(-1). min(-1) (22, 36, and 32%, respectively, greater than control). Nonhepatic glucose uptake increased significantly during delivery of GLP-1 at 5.1 and 10 pmol. kg(-1). min(-1) (25 and 46% greater than control) and tended (P = 0.1) to increase during GLP-1 infusion at 20 pmol. kg(-1). min(-1) (24% greater than control). Intraportal infusion of GLP-1 at high physiological and pharmacological rates increased glucose disposal primarily in nonhepatic tissues.


Asunto(s)
Glucagón/administración & dosificación , Glucosa/metabolismo , Fragmentos de Péptidos/administración & dosificación , Precursores de Proteínas/administración & dosificación , Alanina/sangre , Animales , Glucemia/análisis , Sistema Cardiovascular/efectos de los fármacos , Perros , Ácidos Grasos no Esterificados/sangre , Péptido 1 Similar al Glucagón , Glicerol/sangre , Glucógeno/biosíntesis , Hormonas/sangre , Infusiones Intravenosas , Ácido Láctico/sangre , Hígado/metabolismo , Circulación Hepática/efectos de los fármacos , Concentración Osmolar , Vena Porta
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