Increased number of myocardial voltage-gated Ca2+ channels and unchanged total β-receptor number in long-term streptozotocin-diabetic rats

• Published in: European journal of endocrinology Vol. 134; no. 1; pp. 107 - 113
• Main Authors: GOTZSCHE, L. B.-H, ROSENQVIST, N, GRONBAEK, H, FLYVBJERG, A, GOTZSCHE, O
• Format: Journal Article
• Language: English
• Published: Colchester Portland Press 01-01-1996
• Subjects: Animals; Associated diseases and complications; Biological and medical sciences; Calcium Channels - metabolism; Chronic Disease; Diabetes Mellitus, Experimental - metabolism; Diabetes. Impaired glucose tolerance; Electrophysiology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; EXPERIMENTAL STUDIES; Female; Ion Channel Gating; Medical sciences; Myocardium - metabolism; Rats; Rats, Wistar; Receptors, Adrenergic, beta - metabolism; Thyroxine - blood; Triiodothyronine - blood; Endocrinopathy; Calcium; Rat; Diabetes mellitus; Rodentia; Metabolism; Vertebrata; Experimental disease; Mammalia; Animal; Myocardium; Biological effect; Adrenergic receptor
• ISSN: 0804-4643; 1479-683X
• DOI: 10.1530/eje.0.1340107

Gøtzsche LB-H, Rosenqvist N. Grønbœk H, Flyvbjerg A, Gøtzsche O. Increased number of myocardial voltage-gated Ca2+ channels and unchanged total β-receptor number in long-term streptozotocin-diabetic rats. Eur J Endocrinol 1996;134:107–13. ISSN 0804–4643. In order to elucidate further the abnormal myocardial Ca+ metabolism in diabetes mellitus, voltage-gated Ca2+ channels and β-receptors were quantified in myocardial membranes of short- and long-term diabetic rats. Diabetes was induced by an injection of streptozotocin (STZ). Animals were killed 2, 4, 7, 90 and 200 days after STZ. A group of diabetic animals were treated with insulin for 20 days following 180 days of untreated diabetes. Diabetic animals developed low triiodothyronine syndrome. During short-term diabetes, the maximum binding capacity (MBC) for Ca+ channels was reduced by 25% at day 4 p<0.05) and the β-receptor MBC was reduced by 48% p<0.05). A normalizing tendency was observed at day 7 for both receptor types; insulin-treated rats did not differ from controls at that time. After 90 and 200 days of untreated diabetes the Ca+ channel MBC had increased by 36% and 27%, respectively (p < 0.05). Twenty days of strictly regulated blood glucose following 180 days of untreated diabetes totally normalized the Ca+ channel MBC. This is in contrast to a previous report where insulin treatment did not normalize the Ca+ channel MBC. Total β-receptor MBCs did not differ from control values 90 and 200 days after STZ. In conclusion, an increase in rat myocardial Ca2+ channel MBC during long-term diabetes was fully normalized by short-term insulin treatment. The increase in sarcolemmal Ca2+ channels could serve to compensate for a defect coupling of the β-receptor to adenylate cyclase. An elevated Ca+ channel number may, at least theoretically, lead to increased Ca2+ flow across the cardiac sarcolemma and in this way contribute to the diabetic cardiomyopathy by increasing the intracellular Ca2+ concentration. Liv Bjørn-Hansen Gøtzsche, Dept. of Internal Medicine M, (Diabetes and Endocrinology), Aarhus Kommunehospital, University Hospital of Aarhus, DK-8000 Aarhus C, Denmark.