Increase in [3H]PN 200-110 binding to cardiac muscle membrane in streptozocin-induced diabetic rats.
Voltage-sensitive Ca2+ channels in cardiac left ventricular muscle membranes isolated from nondiabetic control and diabetic rats were measured with [3H]PN 200-110, a dihydropyridine derivative, as a ligand. The binding site (Bmax) of [3H]PN 200-110 in cardiac membranes isolated from streptozocin-induced diabetic (STZ-D) rats (128 +/- 10 fmol/mg protein) significantly (P less than 0.01) increased by 64% compared with that of control rats (78 +/- 4 fmol/mg protein) 10 wk after STZ administration without a significant change in Kd. However, the significant increase in Bmax of [3H]PN 200-110 binding in diabetic rats depended on the duration of diabetes such that the increase was not found until 6 wk after STZ injection. An 8-wk intensive insulin treatment, which was initiated 2 wk after STZ injection, normalized the increase in [3H]PN 200-110 binding in STZ-D rats to control levels (85 +/- 4 fmol/mg protein). Furthermore, [3H]PN 200-110 binding to control cardiac membranes was dose-dependently inhibited in the presence of verapamil, a phenylalkylamine Ca2+ antagonist, but that was not the case in cardiac membranes isolated from STZ-D rats. These results indicate that voltage-sensitive Ca2+ channels in cardiac muscle isolated from STZ-D rats are quantitatively and qualitatively altered, because the course of diabetes and the increase in the channels can be prevented by treatment with insulin.
Nishio
Y
Y
Third Department of Medicine, Shiga University of Medical Science, Japan.
Kashiwagi
A
A
Ogawa
T
T
Asahina
T
T
Ikebuchi
M
M
Kodama
M
M
Shigeta
Y
Y
D000818:Animals; D001665:Binding Sites; D001786:Blood Glucose / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D017275:Isradipine; D008297:Male; D008566:Membranes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010069:Oxadiazoles / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin; D014316:Tritium / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D010069:Oxadiazoles; D014316:Tritium; D013311:Streptozocin; D014700:Verapamil; D002118:Calcium; D017275:Isradipine