RESUMEN
Previously we have reported that, cycloart-23-ene-3ß, 25-diol (called as B2) and L-glutamine stimulated glucagon like peptide-1 (GLP-1) (7-36) amide secretion diabetic rats. The objective of present investigation was to investigate the concomitant administration of cycloart-23-ene-3ß, 25-diol+sitagliptin and L-glutamine+sitagliptin in streptozotocin - nicotinamide induced diabetic Sprague Dawley. Type 2 diabetes was induced in overnight fasted male Sprague Dawley rats pre-treated with nicotinamide (100 mg/kg, i.p.) followed by administration of streptozotocin (55 mg/kg, i.p.) 20 min after. The rats were divided into; I- non-diabetic, II- diabetic control, III- Sitagliptin (5 mg/kg, p.o.)+cycloart-23-ene-3ß, 25-diol (1 mg/kg, p.o.), IV- Sitagliptin (5 mg/kg, p.o.)+L-glutamine (1000 mg/kg, p.o.). The concomitant treatment of cycloart-23-ene-3ß, 25-diol and L-glutamine with sitagliptin was 8 weeks. Plasma glucose, body weight, food and water intake were determined every week. Glycosylated haemoglobin, lipid profile, plasma and colonic active (GLP-1) (7-36) amide, plasma and pancreatic insulin, histology of pancreata and biomarkers of oxidative stress were measured after 8(th) week treatment. Concomitant administration of cycloart-23-ene-3ß, 25-diol and L-glutamine with sitagliptin significantly (p<0.001) reduced plasma glucose, glyoxylated haemoglobin, lipid profile and oxidative stress parameters compared to diabetic control groups. Both concomitant treatment increased plasma and pancreatic insulin as well as plasma and colonic active (GLP-1) (7-36) amide secretion. Histological analysis by Gomori staining observed less destruction of pancreatic ß cells. The result obtained from this study; it is concluded that concomitant administration of cycloart-23-ene-3ß, 25-diol+sitagliptin and L-glutamine+sitagliptin showed additive antihyperglycaemic effect in diabetic rats.
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Péptido 1 Similar al Glucagón/metabolismo , Glutamina/farmacología , Glutamina/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Pirazinas/farmacología , Triazoles/farmacología , Triterpenos/farmacología , Animales , Biomarcadores/metabolismo , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Colon/efectos de los fármacos , Colon/metabolismo , Diabetes Mellitus Experimental/sangre , Conducta de Ingestión de Líquido/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Péptido 1 Similar al Glucagón/sangre , Glutamina/administración & dosificación , Hemoglobina Glucada/metabolismo , Insulina/sangre , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Niacinamida , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Páncreas/patología , Pirazinas/administración & dosificación , Pirazinas/uso terapéutico , Ratas , Ratas Sprague-Dawley , Fosfato de Sitagliptina , Coloración y Etiquetado , Estreptozocina , Triazoles/administración & dosificación , Triazoles/uso terapéutico , Triterpenos/administración & dosificación , Triterpenos/uso terapéuticoRESUMEN
L-glutamine is a non-essential amino acid. It decreased blood sugar, stimulated insulin secretion in type 2 diabetic patients. The objective of the present investigation was to evaluate L-glutamine increases glucagon like peptide-1 (GLP-1) (7-36) amide secretion in streptozotocin-nicotinamide (STZ-NTM) induced diabetic Sprague Dawley rats. Molecular docking study was performed to elucidate the molecular basis for GLP-1 receptor agonistic activity. Type 2 diabetes was induced in overnight fasted Sprague Dawley rats pre-treated with nicotinamide (100 mg/kg, i.p.) followed by 20 min after administration of streptozotocin (55 mg/kg, i.p.). The rats were divided into; I - nondiabetic, II - diabetic control, III - sitagliptin (5 mg/kg, p.o.), IV - L-glutamine (250 mg/kg, p.o.), V - L-glutamine (500 mg/kg, p.o.) and VI - L-glutamine (1000 mg/kg, p.o.). The L-glutamine and sitagliptin treatment was 8 week. Plasma glucose was estimated every week. Body weight, food and water intake were recorded daily. Glycosylated haemoglobin, lipid profile, plasma and colonic active (GLP-1) (7-36) amide, mRNA expression of proglucagon GLP-1, plasma and pancreatic insulin, histology of pancreata and biomarkers of oxidative stress (superoxidase dismutase, reduced glutathione, malondialdehyde, glutathione peroxidase, glutathione S transferase) were measured after 8 week. In acute study, the rats were divided into I - glucose (2.5 g/kg, p.o.), II - sitagliptin (5 mg/kg, p.o.), III - L-glutamine (250 mg/kg, p.o.), IV - L-glutamine (500 mg/kg, p.o.) and V - L-glutamine (1000 mg/kg, p.o.). Plasma glucose, active GLP-1 (7-36) amide concentration and insulin levels were measured after glucose loading. The docking data indicated that l-glutamine bind to the GLP-1 receptor. L-glutamine decreased plasma glucose, increased plasma and pancreatic insulin, increased plasma and colonic active GLP-1 (7-36) amide secretion as well as decreased oxidative stress in streptozotocin-nicotinamide induced diabetic rats.
Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/metabolismo , Péptido 1 Similar al Glucagón/metabolismo , Glutamina/administración & dosificación , Glutamina/farmacología , Niacinamida/efectos adversos , Fragmentos de Péptidos/metabolismo , Administración Oral , Animales , Peso Corporal/efectos de los fármacos , Colon/efectos de los fármacos , Colon/metabolismo , Diabetes Mellitus Experimental/fisiopatología , Ingestión de Líquidos/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Péptido 1 Similar al Glucagón/sangre , Péptido 1 Similar al Glucagón/genética , Receptor del Péptido 1 Similar al Glucagón , Prueba de Tolerancia a la Glucosa , Glutamina/metabolismo , Hemoglobina Glucada/metabolismo , Insulina/sangre , Insulina/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Simulación del Acoplamiento Molecular , Estrés Oxidativo/efectos de los fármacos , Páncreas/efectos de los fármacos , Páncreas/metabolismo , Páncreas/patología , Fragmentos de Péptidos/sangre , Fragmentos de Péptidos/genética , Conformación Proteica , Pirazinas/administración & dosificación , Pirazinas/metabolismo , Pirazinas/farmacología , Ratas , Ratas Sprague-Dawley , Receptores de Glucagón/química , Receptores de Glucagón/metabolismo , Fosfato de Sitagliptina , Triazoles/administración & dosificación , Triazoles/metabolismo , Triazoles/farmacologíaRESUMEN
In previous study, we have reported cycloart-23-ene-3ß, 25-diol is an active antidiabetic constituent isolated from stem bark of Pongamia pinnata (Linn.) Pierre. The objective of the present investigation was to evaluate cycloart-23-ene-3ß, 25-diol stimulates glucagon like peptide-1 (GLP-1) (7-36) amide secretion in streptozotocin-nicotinamide induced diabetic Sprague Dawley rats. Molecular docking studies were performed to elucidate the molecular basis for GLP-1 receptor agonistic activity. Type 2 diabetes was induced in overnight fasted Sprague Dawley rats pre-treated with nicotinamide (100mg/kg, i.p.) followed by administration of streptozotocin (55 mg/kg, i.p.) 20 min after. The rats were divided into following groups; I- non-diabetic, II- diabetic control, III- sitagliptin (5mg/kg, p.o.), IV- cycloart-23-ene-3ß, 25-diol (1mg/kg, p.o.). The cycloart-23-ene-3ß, 25-diol and sitagliptin treatment was 8 week. Plasma glucose was estimated every week (week 0 to week 8). Body weight, food and water intake were recorded daily. Glycosylated haemoglobin, lipid profile, plasma and colonic active (GLP-1) (7-36) amide, mRNA expression of proglucagnon GLP-1, plasma and pancreatic insulin, histology of pancreata as well as biomarkers of oxidative stress (superoxidase dismutase, reduced glutathione, malondialdehyde, glutathione peroxidase, glutathione S transferase) were measured after 8th week treatment. In acute study, active GLP-1 (7-36) amide release, plasma glucose and insulin were measured during oral glucose tolerance test. The docking data clearly indicated cycloart-23-ene-3ß, 25-diol bind to the GLP-1 receptor. It decreased plasma glucose level, increased plasma and pancreatic insulin level as well as increased plasma and colonic active GLP-1 (7-36) amide secretion in streptozotocin-nicotinamide induced diabetic Sprague Dawley rats.