Abstract | AIMS/HYPOTHESIS: 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/INTERPRETATION: 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.
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Authors | Kazi Rafiq, Yoshihide Fujisawa, Shamshad J Sherajee, Asadur Rahman, Abu Sufiun, Hiroyuki Kobori, Hermann Koepsell, Masaki Mogi, Masatsugu Horiuchi, Akira Nishiyama |
Journal | Diabetologia
(Diabetologia)
Vol. 58
Issue 12
Pg. 2885-98
(Dec 2015)
ISSN: 1432-0428 [Electronic] Germany |
PMID | 26450431
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Sodium-Glucose Transporter 2
- Glucose
- Norepinephrine
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Topics |
- Animals
- Blood Pressure
- Diabetes Mellitus, Type 2
(metabolism, pathology)
- Glucose
(metabolism)
- Glucose Clamp Technique
- Glycosuria
(metabolism)
- Humans
- Kidney
(innervation, metabolism, pathology)
- Nephrectomy
- Norepinephrine
(blood)
- Prediabetic State
(metabolism)
- Rats
- Rats, Inbred OLETF
- Sodium-Glucose Transporter 2
(metabolism)
- Sympathectomy
- Sympathetic Nervous System
(physiopathology)
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