title: Sodium Intake Regulates Glucose Homeostasis through the PPARδ/Adiponectin-Mediated SGLT2 Pathway.
abstract: High sodium intake is a major risk factor for developing hypertension in diabetes. Promotion of sodium excretion reduces cardiometabolic lesions in diabetes. However, the interaction between sodium intake and glucose homeostasis remains elusive. Here, we report that high sodium intake remarkably increased natriuresis in wild-type mice, but this effect was blunted in adipose-specific PPARδ knockout mice and diabetic mice. PPARδ activation in perirenal fat by agonist or high sodium intake inhibited renal sodium-glucose cotransporter 2 (SGLT2) function, which is mediated by increased production of adipose adiponectin. In addition, high salt intake-induced natriuresis was impaired in diabetic states because of renal SGLT2 dysfunction. Type 2 diabetic patients with uncontrolled hyperglycemia had less natriuresis that was correlated to their plasma adiponectin levels. Our findings provide insights into the distinctive role of the PPARδ/adiponectin/SGLT2 pathway in the regulation of sodium and glucose homeostasis.
authors.affiliation: Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.affiliation: Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Sun
authors.affiliation: Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Zongshi
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Yuanting
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Xiong
authors.affiliation: Department of Cardiology, Affiliated Hospital of Zunyi Medical College, Institute of Clinical Medicine of Zunyi Medical College, Zunyi, Guizhou 563000, China.
authors.forename: Qianhui
authors.initials: Q
authors.lastname: Shang
authors.affiliation: Department of Pharmacology and Pharmacy, University of Hong Kong, Pok Fu Lam, Hong Kong, China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.affiliation: Institute of Vascular Medicine and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Sha Tin, Hong Kong, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
authors.forename: Daoyan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China. Electronic address: zhuzm@yahoo.com.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D051379:Mice; D047494:PPAR delta / Q000378:metabolism*; D015398:Signal Transduction; D012982:Sodium, Dietary / Q000378:metabolism*; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism*
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D047494:PPAR delta; D012982:Sodium, Dietary; D051297:Sodium-Glucose Transporter 2