title: Role of the renal sympathetic nerve in renal glucose metabolism during the development of type 2 diabetes in rats.
abstract: OBJECTIVE
  Recent clinical studies have shown that renal sympathetic denervation (RDX) improves glucose metabolism in patients with resistant hypertension. We aimed to elucidate the potential contribution of the renal sympathetic nervous system to glucose metabolism during the development of type 2 diabetes.
  
  
  METHODS
  Uninephrectomised diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats underwent RDX at 25 weeks of age and were followed up to 46 weeks of age.
  
  
  RESULTS
  RDX decreased plasma and renal tissue noradrenaline (norepinephrine) levels and BP. RDX also improved glucose metabolism and insulin sensitivity, which was associated with increased in vivo glucose uptake by peripheral tissues. Furthermore, RDX suppressed overexpression of sodium-glucose cotransporter 2 (Sglt2 [also known as Slc5a2]) in renal tissues, which was followed by an augmentation of glycosuria in type 2 diabetic OLETF rats. Similar improvements in glucose metabolism after RDX were observed in young OLETF rats at the prediabetic stage (21 weeks of age) without changing BP.
  
  
  CONCLUSIONS
  Here, we propose the new concept of a connection between renal glucose metabolism and the renal sympathetic nervous system during the development of type 2 diabetes. Our data demonstrate that RDX exerts beneficial effects on glucose metabolism by an increase in tissue glucose uptake and glycosuria induced by Sglt2 suppression. These data have provided a new insight not only into the treatment of hypertensive type 2 diabetic patients, but also the pathophysiology of insulin resistance manifested by sympathetic hyperactivity.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan. krafiq73@yahoo.com.
authors.forename: Kazi
authors.initials: K
authors.lastname: Rafiq
authors.affiliation: Life Science Research Center, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujisawa
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.
authors.forename: Shamshad J
authors.initials: SJ
authors.lastname: Sherajee
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.
authors.forename: Asadur
authors.initials: A
authors.lastname: Rahman
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.
authors.forename: Abu
authors.initials: A
authors.lastname: Sufiun
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobori
authors.affiliation: Department of Molecular Plant Physiology and Biophysics, University of Würzburg, Julius-von-Sachs-Institute, Julius-von-Sachs-Platz 2, 97082, Würzburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Koepsell
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Graduate School of Medicine, Ehime University, Matsuyama, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mogi
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Graduate School of Medicine, Ehime University, Matsuyama, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Horiuchi
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
mesh_terms: D000818:Animals; D001794:Blood Pressure; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006029:Glycosuria / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000294:innervation* / Q000378:metabolism* / Q000473:pathology; D009392:Nephrectomy; D009638:Norepinephrine / Q000097:blood; D011236:Prediabetic State / Q000378:metabolism; D051381:Rats; D020334:Rats, Inbred OLETF; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000503:physiopathology*
chemical_list: D051297:Sodium-Glucose Transporter 2; D005947:Glucose; D009638:Norepinephrine
keywords: Blood pressure; Glucose metabolism; Insulin resistance; Renal sympathetic denervation (RDX); Sglt2; Slc5a2; Sodium-glucose cotransporter 2; Type 2 diabetes