Nitrochalcones: potential in vivo insulin secretagogues.
In this study, the in vivo and in vitro anti-hyperglycemic activity of chalcone derivatives of 3,4-methylenedioxy, with a substituent electron-acceptor nitro group in the A or B ring, was investigated. As expected, the second generation sulfonylurea glipizide stimulated insulin secretion and reduced glycemia over the study period. Also, it was demonstrated for the first time that chalcones are able to increase insulin secretion and this event was coincident with serum glucose-lowering in the oral glucose tolerance test. Additionally, the chalcones studied had a similar effect on insulin secretion and serum glucose-lowering as glipizide. The effect of chalcones in terms of inducing insulin secretion was greater than that of glipizide after 30 min. Moreover, chalcones were not able to stimulate glucose uptake in soleus muscle, either in the presence of insulin or in the absence of this hormone. In addition, the oral treatment with chalcones did not alter glycemia in diabetic rats. These reports indicate that the effect of chalcones on serum glucose-lowering in hyperglycemic-normal rats is mainly a consequence of insulin secretion, highlighting these chalcones as novel compounds with strong anti-hyperglycemic properties.
Damazio
Rosangela Guollo
RG
Universidade Federal de Santa Catarina, Departamento de Bioquímica, Centro de Ciências Biológicas, Campus Universitário, Florianópolis, SC, Brazil.
Zanatta
Ana Paula
AP
Cazarolli
Luisa Helena
LH
Mascarello
Alessandra
A
Chiaradia
Louise Domeneghini
LD
Nunes
Ricardo José
RJ
Yunes
Rosendo Augusto
RA
Silva
Fátima Regina Mena Barreto
FR
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D002599:Chalcone / Q000008:administration & dosage / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood; D005913:Glipizide / Q000008:administration & dosage / Q000494:pharmacology*; D005947:Glucose / Q000032:analysis; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D002599:Chalcone; D005947:Glucose; D005913:Glipizide