Sympathetic modulation of the renal glucose transporter GLUT2 in diabetic rats.
We have previously shown that the abolition of renal sympathetic nervous activity (RSNA) can influence cortical GLUT1 expression in diabetic rats. However, no study has examined the effects of nervous activity on expression of GLUT2, the major glucose transporter in proximal renal tubules, which participates in renal glucose handling. The aim of this study was to determine whether sympathetic activity modulates renal GLUT2 content. We studied diabetic and nondiabetic rats with normal, low, or high RSNA. The low-RSNA experiment used four groups of Wistar male rats: Wistar sham-operated, Wistar renal-denervated, Diabetic sham-operated, and Diabetic renal-denervated. The high-RSNA experiment used four groups of Wistar-Kyoto male rats: WKY (control), WKY-Diabetic, SHR (spontaneously hypertensive rats), and SHR-Diabetic. Renal denervation was confirmed by a decrease in intrarenal norepinephrine levels and sympathetic hyperactivity, by measurement of RSNA. Western blotting was used to determine the renal cortical GLUT2 protein content, and 24-h urinary sodium and glucose levels were also evaluated. Compared with controls (Wistar and WKY), diabetes increased the GLUT2 protein content in normal-RSNA Diabetics (47%) and WKY-Diabetics (83%). The renal denervation-induced decrease in RSNA reduced the GLUT2 content in both normal and diabetic rats (-21% and -15%, respectively). Compared to WKY rats, SHR presented elevated RSNA and also showed an increase in renal GLUT2 content (17%). Diabetes caused a major increase in GLUT2 protein (52%) in the SHR. These results demonstrate a direct relationship between RSNA and GLUT2 levels; they also reveal an additive effect of sympathetic hyperactivity and diabetes on GLUT2 expression, suggesting a new mechanism for modulating protein expression in renal tissue.
Schaan
Beatriz D'Agord
BD
Instituto de Cardiologia do RS/Fundação Universitária de Cardiologia, Porto Alegre, RS, CEP 90620-001, Brazil. pesquisa@cardiologia.org.br
Irigoyen
Maria Cláudia
MC
Lacchini
Silvia
S
Moreira
Edson Dias
ED
Schmid
Helena
H
Machado
Ubiratan Fabres
UF
D000704:Analysis of Variance; D000818:Animals; D017763:Autonomic Denervation / Q000379:methods; D001794:Blood Pressure / Q000502:physiology; D015153:Blotting, Western / Q000379:methods; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D004231:Diuresis / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D051273:Glucose Transporter Type 2; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009318:Natriuresis / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D012964:Sodium / Q000652:urine; D013311:Streptozocin; D013564:Sympathetic Nervous System / Q000502:physiology*
D051273:Glucose Transporter Type 2; D009004:Monosaccharide Transport Proteins; D013311:Streptozocin; D012964:Sodium; D005947:Glucose; D009638:Norepinephrine