OS 33-04 REGULATION OF SGLT-2 BY THE SYMPATHETIC NERVOUS SYSTEM. (September 2016)

• Record Type: Journal Article
• Authors: Schlaich, Markus; Elliott, Rosemary; Rudnicka, Caroline; Matthews, Vance
• Is Part Of: Journal of hypertension. Volume 34:(2016) Supplement 1
• Publication Date: 2016-09
• Subjects: Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/01.hjh.0000501008.46096.cd
• Languages: English
• ISSNs: 1473-5598

Abstract

Abstract : Objective: Sympathetic nervous system activation is a common feature in various metabolic disorders such as obesity, metabolic syndrome, and type-2 diabetes. The sodium glucose co-transporter 2 (SGLT-2) mediates re-absorption of glucose from the renal proximal tubules. SGLT-2 inhibitors have attracted substantial attention due to their glucose and blood pressure lowering effects. Furthermore, the SGLT-2 inhibitor empagliflozin has recently been associated with improved cardiovascular outcomes in patients with type 2 diabetes. We hypothesized that sympathetic nervous system induced alterations of glucose metabolism may be mediated via regulation of SGLT-2 and investigated whether SGLT-2 is up-regulated by norepinephrine (NE), the main neurotransmitter released from sympathetic neurons. Design and Method: We used the human renal proximal tubule cell line HK2 to assess changes in SGLT-2 expression in response to a range of NE concentrations (0, 0.01, 0.1, 1 and 10 μM) at 24, 48 and 72 h. Results: Bioactivity of NE was confirmed by detection of elevated phosphorylated ERK1/2 using Western Blotting. The absence of cytotoxic effects of NE to HK2 cells was determined using a MTT assay at 24, 48 and 72 h post-treatment. SGLT-2 expression in HK2 cells in response to treatment with NE was determined by immunocytochemistry at 24, 48 and 72 h post-treatment and a marked increase in SGLT-2 expression could be demonstrated. Furthermore, 0.1 and 0.01 μM of NE resulted in significantly increased IL-6 release from HK2 cells compared to the 0 μM negative control. Conclusions: Our in vitro study provides first evidence to suggest that SGLT-2 is up-regulated by NE and indicates a potential role for sympathetic regulation of SGLT-2-mediated renal glucose re-absorption.