Is it time to think about the sodium glucose co-transporter 2 sympathetically?

Nephrology (Carlton). 2016 Apr;21(4):286-94. doi: 10.1111/nep.12620.

Abstract

Disturbances in glucose homeostasis are a key feature of the metabolic syndrome and type 2 diabetes. Renal glucose reabsorption is an important factor in glycaemic control. Glucose reabsorption in the proximal tubules is mediated by the sodium glucose co-transporter 2. The capacity for glucose reabsorption is increased in type 2 diabetes and contributes significantly to hyperglycaemia and impaired glucose control. Understanding the mechanisms underpinning the regulation of the sodium glucose co-transporter 2 is therefore of high clinical relevance. However, despite recent advances in the field and the availability of pharmacological inhibitors of this glucose transporter for the treatment of type 2 diabetes, the mechanisms that regulate sodium glucose co-transporter 2 expression are not fully understood. The sympathetic nervous system is an important modulator of glucose homeostasis, and sympathetic hyperactivity is a characteristic feature of obesity, the metabolic syndrome and type 2 diabetes. Sympathetic inhibition either achieved pharmacologically or by renal sympathetic denervation has been associated with improved glucose control. Importantly, sympathetic nerves innervate the proximal tubules of the kidney where they have been shown to regulate the expression of other transporters such as the sodium hydrogen exchanger 3. This review aims to explore the evidence for the regulation of sodium glucose co-transporter 2-mediated glucose reabsorption by the sympathetic nervous system.

Keywords: glucose; norepinephrine; sodium glucose co-transporter 2; sympathetic nervous system; type 2 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetes Mellitus, Type 2 / therapy
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Kidney / drug effects
  • Kidney / innervation*
  • Kidney / metabolism
  • Renal Reabsorption
  • Sodium-Glucose Transporter 2 / metabolism*
  • Sodium-Glucose Transporter 2 Inhibitors
  • Sympathectomy
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / physiopathology*
  • Sympathetic Nervous System / surgery
  • Sympatholytics / therapeutic use

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Sympatholytics