Vitis vinifera L. grape skin extract activates the insulin-signalling cascade and reduces hyperglycaemia in alloxan-induced diabetic mice.
OBJECTIVE
This study examined the effect of Vitis vinifera grape skin extract (ACH09) on hyperglycaemia and the insulin-signalling cascade in alloxan-treated mice.


METHODS
Glycaemia, serum insulin and Western blot analysis of insulin cascade proteins were evaluated in the gastrocnemius muscles of four groups of adult mice: control, ACH09 (200 mg/kg per day, p.o.), alloxan (300 mg/kg, i.p.) and alloxan + ACH09. Insulin secretion in isolated pancreatic islets was also studied.


RESULTS
Glycaemia values in the alloxan + ACH09 and ACH09 groups were significantly lower than in the alloxan-treated and control groups, respectively. Increased insulin resistance (HOMA index) was observed in the alloxan-treated group but not in the alloxan + ACH09 group. Insulin receptor content and Akt phosphorylation were significantly greater in the alloxan + ACH09 group compared with the alloxan-treated group. The glucose transporter (GLUT-4) content was reduced in alloxan-treated mice compared with the control group, while alloxan + ACH09 and ACH09-treated mice showed a significant increase in GLUT-4 content. ACH09 treatment did not change glucose-induced insulin secretion in isolated pancreatic islets.


CONCLUSIONS
The results suggest that ACH09 has hypoglycaemic and antihyperglycaemic effects that are independent of an increase in insulin release but are probably dependent on an increase in insulin sensitivity resulting from an activation of the insulin-signalling cascade in skeletal muscle.
Department of Pharmacology of Rio de Janeiro State University, Brazil. rsoaresdemoura@pesquisador.cnpq.br
Roberto
R
Soares de Moura
Giselle França
GF
da Costa
Annie Seixas Bello
AS
Moreira
Emerson Ferreira
EF
Queiroz
Daniele Dal Col
DD
Moreira
Erica Patrícia
EP
Garcia-Souza
Angela Castro
AC
Resende
Aníbal Sanchez
AS
Moura
Michelle Teixeira
MT
Teixeira
D000496:Alloxan; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D004195:Disease Models, Animal; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood*; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D011972:Receptor, Insulin / Q000378:metabolism; D027843:Vitis / Q000737:chemistry*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D000496:Alloxan; D011972:Receptor, Insulin