[Protective effect of losartan on insulin secretion function of RIN-m cells against angiotensin II-induced injury and the mechanism].
OBJECTIVE
To investigate the protective effect of losartan against angiotensin II (AngII)-induced beta cell (RIN-m) impairment and explore its mechanism.


METHODS
In vitro cultured RIN-m cells were divided into control group, 100 nmol/L AngII group and losartan pretreatment group. After cell incubation with the corresponding agents for 24 h, the amount of basal (3.3 mmol/L) and glucose-stimulated (16.7 mmol/L) insulin secretion (GSIS) was detected by radioimmunoassay, and the cellular reactive oxygen species (ROS) was assayed by flow cytometry with DCFH-DA staining; the mRNA and protein expressions of uncoupling protein 2 (UCP2) were determined by RT-PCR and Western blotting, respectively.


RESULTS
The basal insulin secretion showed no significant differences between the 3 groups (P>0.05). The GSIS in 100 nmol/L AngII group was significantly lower than that of the control group (P<0.001), but losartan pretreatment markedly restored the insulin secretion function to a level comparable to that of the control group (P<0.05). Compared with the control group, 100 nmol/L AngII significantly increased the cellular ROS level and the mRNA and protein expressions of UCP2 (P<0.05), and these changes were eliminated by losartan pretreatment.


CONCLUSIONS
Losartan pretreatment offers protective effect against AngII-induced impairment of the GSIS of beta cells possibly by antagonizing the effects of AngII that causes increased ROS level and UCP2 expressions in beta-cells.
Lu
Xin
X
Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China. lusia716@126.com
Lv
Jun
J
Zhang
Hua
H
Chen
Hong
H
Cai
De-hong
DH
D000804:Angiotensin II / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D007340:Insulinoma / Q000473:pathology; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D000071246:Uncoupling Protein 2
D000959:Antihypertensive Agents; D007473:Ion Channels; D024101:Mitochondrial Proteins; D020011:Protective Agents; D012333:RNA, Messenger; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D000804:Angiotensin II; D019808:Losartan