Correction of glycaemia and GLUT1 level by mildronate in rat streptozotocin diabetes mellitus model.
Anti-ischaemic drug mildronate suppresses fatty acid metabolism and increases glucose utilization in myocardium. It was proposed that it could produce a favourable effect on metabolic parameters and glucose transport in diabetic animals. Rats with streptozotocin diabetes mellitus were treated with mildronate (100 mg/kg daily, per os, 6 weeks). Therapeutic effect of mildronate was monitored by measuring animal weight, concentrations of blood glucose, insulin, blood triglycerides, free fatty acids, blood ketone bodies and cholesterol, glycated haemoglobin per cent (HbA1c%) and glucose tolerance. GLUT1 mRNA and protein expression in kidneys, heart, liver and muscles were studied by means of real time RT-PCR and immunohistochemistry correspondingly. In the streptozotocin + mildronate group, mildronate treatment caused a significant decrease in mean blood glucose, cholesterol, free fatty acid and HbA1c concentrations and improved glucose tolerance. Induction of streptozotocin diabetes mellitus provoked increase of both GLUT1 gene and protein expression in kidneys, heart and muscle, mildronate treatment produced normalization of the GLUT1 expression levels. In the liver a similar effect was observed for GLUT1 protein expression, while GLUT1 gene expression was increased by mildronate. Mildronate produces therapeutic effect in streptozotocin diabetes model. Mildronate normalizes the GLUT1 expression up-regulated by streptozotocin diabetes mellitus in kidneys, heart, muscle and liver. Copyright © 2011 John Wiley & Sons, Ltd.
Latvian Institute of Organic Synthesis, Riga, Latvia. lizsjak@yahoo.com
Jelizaveta
J
Sokolovska
Sergejs
S
Isajevs
Olga
O
Sugoka
Jelena
J
Sharipova
Lasma
L
Lauberte
Darja
D
Svirina
Evita
E
Rostoka
Tatjana
T
Sjakste
Ivars
I
Kalvinsh
Nikolajs
N
Sjakste
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D049628:Body Size / Q000187:drug effects; D003920:Diabetes Mellitus / Q000188:drug therapy; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism; D005951:Glucose Tolerance Test; D051272:Glucose Transporter Type 1 / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D008763:Methylhydrazines / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000009:adverse effects / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
D001786:Blood Glucose; D005227:Fatty Acids; D051272:Glucose Transporter Type 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008763:Methylhydrazines; D012333:RNA, Messenger; D013311:Streptozocin; D014280:Triglycerides; C050147:3-(2,2,2-trimethylhydrazine)propionate