TRB3 is involved in free fatty acid-induced INS-1-derived cell apoptosis via the protein kinase C δ pathway.
Chronic exposure to free fatty acids (FFAs) may induce β cell apoptosis in type 2 diabetes. However, the precise mechanism by which FFAs trigger β cell apoptosis is still unclear. Tribbles homolog 3 (TRB3) is a pseudokinase inhibiting Akt, a key mediator of insulin signaling, and contributes to insulin resistance in insulin target tissues. This paper outlined the role of TRB3 in FFAs-induced INS-1 β cell apoptosis. TRB3 was promptly induced in INS-1 cells after stimulation by FFAs, and this was accompanied by enhanced INS-1 cell apoptosis. The overexpression of TRB3 led to exacerbated apoptosis triggered by FFAs in INS-1-derived cell line and the subrenal capsular transplantation animal model. In contrast, cell apoptosis induced by FFAs was attenuated when TRB3 was knocked down. Moreover, we observed that activation and nuclear accumulation of protein kinase C (PKC) δ was enhanced by upregulation of TRB3. Preventing PKCδ nuclear translocation and PKCδ selective antagonist both significantly lessened the pro-apoptotic effect. These findings suggest that TRB3 was involved in lipoapoptosis of INS-1 β cell, and thus could be an attractive pharmacological target in the prevention and treatment of T2DM.
Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Jun
J
Qin
Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
Ni
N
Fang
Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
Jinning
J
Lou
Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
Wenjian
W
Zhang
Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
Shiqing
S
Xu
Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
Honglin
H
Liu
Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
Qing
Q
Fang
Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
Zai
Z
Wang
Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, China.
Jiang
J
Liu
Department of Pathophysiology, North China Coal Medical University, Tangshan, China.
Xiuli
X
Men
Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
Liang
L
Peng
Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Li
L
Chen
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D019308:Palmitic Acid / Q000494:pharmacology*; D051745:Protein Kinase C-delta / Q000378:metabolism*; D021381:Protein Transport; D015398:Signal Transduction / Q000187:drug effects
D018797:Cell Cycle Proteins; C474830:TRB3 protein, mouse; D019308:Palmitic Acid; D051745:Protein Kinase C-delta; D053148:Caspase 3; D053179:Caspase 7