Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor Increases Circulating Zinc-Α2-Glycoprotein Levels in Patients with Type 2 Diabetes.
ZAG has recently been characterized as a potent metabolic regulator, but the effect of anti-diabetic agents on ZAG in humans remains unknown. Our aim was to study the effects of SGLT2 inhibitor on circulating ZAG and ADI in nT2DM. 162 subjects with nT2DM were treated by a placebo or DAPA. After 3-months of DAPA therapy, HbA1c, FBG, 2h-PBG, FFA, TG, blood pressure, BMI, WHR, body weight, FAT%, FINS, and HOMA-IR in T2DM patients decreased significantly, whereas HDL-C was significantly increased. Importantly, circulating ZAG and ADI levels in these patients were also significantly increased after DAPA therapy. Basal ZAG levels were associated with changes in BMI, FAT%, TC, HbA1c, HDL-C and ADI at post-treatment, whereas basal ADI levels were associated with changes in FAT%, TC, HbA1c, FFA and HDL-c. In vitro, DAPA treatment showed increased ZAG expression and secretion in HepG2 cells. When combined with a PPAR-γinhibitor GW9662, the effect of DAPA on ZAG was abrogated. These findings suggest that circulating ZAG can be regulated by DAPA, and DAPA promotes the expression and secretion of ZAG in the liver via the activation of PPAR-γ. The changes in ZAG induced by DAPA may play a physiologic role in enhancing insulin sensitivity.
Department of Endocrinology, the Affiliated Hospital, Zunyi Medical University, 563003 Guizhou, China.
Xin
X
Liao
Department of Endocrinology, the Affiliated Hospital, Zunyi Medical University, 563003 Guizhou, China.
Xuemei
X
Wang
Department of Endocrinology, the Affiliated Hospital, Zunyi Medical University, 563003 Guizhou, China.
Haopeng
H
Li
Key Laboratory of Diagnostic Medicine (Ministry of Education) and Department of Clinical Biochemistry, College of Laboratory Medicine, Chongqing Medical University, 400016, China.
Ling
L
Li
Department of Endocrinology, the Affiliated Hospital, Zunyi Medical University, 563003 Guizhou, China.|Staff Hospital of Guizhou Maotal Mistillery Group Company, Renhual, 564500, Guizhou, China.
Guohao
G
Zhang
Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China.
Mengliu
M
Yang
Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China.
Lei
L
Yuan
Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.
Hua
H
Liu
Department of Endocrinology, the Affiliated Hospital, Zunyi Medical University, 563003 Guizhou, China.|Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 400010 Chongqing, China.
Gangyi
G
Yang
Department of Endocrinology, the Affiliated Hospital, Zunyi Medical University, 563003 Guizhou, China.
Lin
L
Gao
D054392:Adipokines; D000328:Adult; D002352:Carrier Proteins / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000187:drug effects / Q000378:metabolism; D011446:Prospective Studies; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism*; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000090203:Zn-Alpha-2-Glycoprotein
D054392:Adipokines; D002352:Carrier Proteins; D006023:Glycoproteins; D047495:PPAR gamma; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C488891:AZGP1 protein, human; D000090203:Zn-Alpha-2-Glycoprotein; C089180:SLC5A2 protein, human