The effect of metformin on insulin receptors and lipid peroxidation in alloxan and streptozotocin induced diabetes.
Biguanides are used for the treatment of non-insulin dependent diabetes mellitus but there is no evidence for an improving action of biguanide on the enhancement of peripheral glucose disposal in type 1 diabetes. It is known that biguanide agents reduce the oxidation of free fatty acids. Using alloxan and streptozotocin (STZ) induced diabetic rats as a model for type 1 diabetes mellitus, we measured insulin binding capacity and plasma lipid peroxidation levels before and after metformin induction. There was a significant increase in insulin binding capacity and lipid peroxidation levels in alloxan and STZ diabetes compared to controls. We examined the effect of metformin on alloxan and STZ-induced diabetic rats. In alloxan-induced diabetes metformin (Met) treatment led to an increase in insulin receptor number in liver plasma membranes (before Met: 46.50 +/- 2.69, after Met: 76.00 +/- 3.39 fmol/mg, p < 0.001) and a decrease in plasma lipid peroxidation levels compared to the non-treated group (before Met: 1.85 +/- 0.53, after Met: 1.10 +/- 0.09 nmol MDA/ml, p < 0.05). In STZ-induced diabetic rats metformin treatment did not change the lipid peroxidation levels (before Met: 1.26 +/- 0.31, after Met: 1.38 +/- 0.44 nmol MDA/ml, p > 0.05) whereas it did increase the receptor numbers (before Met: 41.60 +/- 4.33, after Met: 63.40 +/- 8.64 fmol/mg, p < 0.002).
Kanigür-Sultuybek
G
G
Department of Medical Biology, Cerrahpaşa Medical School, Istanbul University, Turkey.
Güven
M
M
Onaran
I
I
Tezcan
V
V
Cenani
A
A
Hatemi
H
H
D000496:Alloxan; D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D051381:Rats; D011972:Receptor, Insulin / Q000187:drug effects*; D013311:Streptozocin
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D013311:Streptozocin; D000496:Alloxan; D008687:Metformin; D011972:Receptor, Insulin