Lowered insulin-sensitive Ca2+ transport in cultured glomerular mesangial cells from spontaneously hypertensive rats.
Insulin-resistant state has been postulated in the pathogenesis of hypertension. To investigate the role of insulin in Ca2+ regulation of the glomerular mesangial cell (MC) in hypertension, the effect of insulin on Ca2+ transport and intracellular-free calcium concentration ([Ca2+]i) was measured in serially passaged cultured MC obtained from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Insulin produced a substantial increase in 45Ca uptake as well as [Ca2+]i in quiescent cultured MC from both strains. These stimulatory effects of insulin were completely inhibited by diltiazem, and partially inhibited by H-7, TMB-8 and 5-N,N (hexamethylene) amiloride (HMA), but were not inhibited by W-7 or trifluoroperazine. Although basal ([Ca2+]i) values were not different, insulin-sensitive 45Ca uptake of SHR MC was significantly less than that of WKY MC. Insulin-sensitive increase in ([Ca2+]i) of SHR MC was also less than that of WKY MC. We concluded that insulin increased 45Ca uptake, leading to an increase in ([Ca2+]i), presumably through the voltage-dependent Ca2+ channel, intracellular Ca2+ release and/or proteinkinase C-mediated mechanisms in cultured MC. Blunted response of insulin-sensitive Ca2+ uptake and ([Ca2+]i) in SHR MC suggested differential regulation of Ca2+ transport in response to insulin in the kidney with primary hypertension.
Kuriyama
S
S
Division of Nephrology, Saiseikai Central Hospital, Tokyo, Japan.
Tomonari
H
H
Segawa
H
H
Horiguchi
M
M
Hashimoto
T
T
Sakai
O
O
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D007328:Insulin; D002118:Calcium