Possible Increase in Serum FABP4 Level Despite Adiposity Reduction by Canagliflozin, an SGLT2 Inhibitor.
Possible Increase in Serum FABP4 Level Despite Adiposity Reduction by Canagliflozin, an SGLT2 Inhibitor.
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DOI：
10.1371/journal.pone.0154482
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Miura T
中科院分区：
文献类型：
--
作者：
Furuhashi M;Matsumoto M;Hiramitsu S;Omori A;Tanaka M;Moniwa N;Yoshida H;Ishii J;Miura T
脂肪酸结合蛋白4（FABP 4/A-FABP/aP 2）是由脂肪细胞分泌的，与儿茶酚胺诱导的脂解有关，血清FABP 4水平升高与肥胖、胰岛素抵抗和动脉粥样硬化有关。FABP 4作为一种新的脂肪因子，通过增加肝脏葡萄糖生成（HGP）导致胰岛素抵抗。钠-葡萄糖协同转运蛋白2（SGLT 2）抑制剂通过增加尿糖排泄降低血糖水平，但HGP增强。在此，我们研究了卡格列净（一种SGLT 2抑制剂）是否可调节血清FABP 4水平。2型糖尿病患者（n = 39）接受卡格列净（100 mg/天）给药12周。治疗前后测定血清FABP 4水平。基线时，血清FABP 4水平与肥胖、肾功能不全和去甲肾上腺素水平相关。卡格列净治疗显著降低了肥胖以及空腹血糖和HbA 1c水平，但平均血清FABP 4水平升高了10.3%（18.0 ± 1.0 vs. 19.8 ± 1.2 ng/ml，P = 0.008），尽管在39例患者中的26例（66.7%）中观察到治疗后FABP 4水平升高。FABP 4水平变化与空腹血糖（r = 0.329，P = 0.044）、糖化血红蛋白（r = 0.329，P = 0.044）和去甲肾上腺素（r = 0.329，P = 0.041）水平变化呈正相关，但与肥胖或其他变量变化无显著相关性。尽管卡格列净改善了葡萄糖代谢并减少了肥胖，但在一些糖尿病患者中，卡格列净反而增加了血清FABP 4水平，可能是通过诱导脂肪细胞中的儿茶酚胺诱导的脂解。卡格列净导致的FABP 4水平升高可能破坏葡萄糖代谢的改善，可能是通过抑制SGLT 2导致HGP升高的可能机制。UMIN-CTR临床试验UMIN 000018151
Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) is secreted from adipocytes in association with catecholamine-induced lipolysis, and elevated serum FABP4 level is associated with obesity, insulin resistance and atherosclerosis. Secreted FABP4 as a novel adipokine leads to insulin resistance via increased hepatic glucose production (HGP). Sodium-glucose cotransporter 2 (SGLT2) inhibitors decrease blood glucose level via increased urinary glucose excretion, though HGP is enhanced. Here we investigated whether canagliflozin, an SGLT2 inhibitor, modulates serum FABP4 level. Canagliflozin (100 mg/day) was administered to type 2 diabetic patients (n = 39) for 12 weeks. Serum FABP4 level was measured before and after treatment. At baseline, serum FABP4 level was correlated with adiposity, renal dysfunction and noradrenaline level. Treatment with canagliflozin significantly decreased adiposity and levels of fasting glucose and HbA1c but increased average serum FABP4 level by 10.3% (18.0 ± 1.0 vs. 19.8 ± 1.2 ng/ml, P = 0.008), though elevation of FABP4 level after treatment was observed in 26 (66.7%) out of 39 patients. Change in FABP4 level was positively correlated with change in levels of fasting glucose (r = 0.329, P = 0.044), HbA1c (r = 0.329, P = 0.044) and noradrenaline (r = 0.329, P = 0.041) but was not significantly correlated with change in adiposity or other variables. Canagliflozin paradoxically increases serum FABP4 level in some diabetic patients despite amelioration of glucose metabolism and adiposity reduction, possibly via induction of catecholamine-induced lipolysis in adipocytes. Increased FABP4 level by canagliflozin may undermine the improvement of glucose metabolism and might be a possible mechanism of increased HGP by inhibition of SGLT2. UMIN-CTR Clinical Trial UMIN000018151