Regulation of sodium-glucose cotransporter SGLT1 in the intestine of hypertensive rats.
Experimental models of hypertension, such as spontaneously hypertensive rats (SHR), show alterations in cellular sodium transport that affects Na(+)-coupled cotransport processes and has been involved in the pathogenesis of this disease. The objective of the present study was to analyze the kinetic properties of the sodium-dependent glucose transport in the jejunum and ileum of SHR and its genetic control, Wistar-Kyoto (WKY) rats, as well as the regulation of the transporter, SGLT1. In hypertensive rats, the increased systolic blood pressure was accompanied by an enhancement of serum aldosterone levels compared with WKY rats, but no alterations were found in their body weight or serum glucose/insulin levels. The values for d-glucose maximal rate of transport (V(max)) were 42 and 60% lower, respectively, in the jejunum and ileum of SHR than those from WKY rats. On the other hand, the values for the Michaelis constant (K(m)) were similar in both animal groups, as was the diffusive component of transport (K(d)). Immunoblotting and Northern blot analysis revealed the existence of a lower abundance of SGLT1 protein and mRNA in SHR. Moreover, hypertensive rats showed a decrease in the molecular mass of SGLT1 that could not be explained in terms of different glycosylation and/or phosphorylation levels or an alternative splicing in the expression of the protein. These findings demonstrate that SGLT1 is regulated at a transcriptional level in the intestine of hypertensive rats, and suggest that this transporter might participate in the dysregulation of sodium transport observed in hypertension.
Mate
Alfonso
A
Department of Physiology and Zoology, University of Seville, Spain.
Barfull
Anna
A
Hermosa
Angeles M
AM
Gómez-Amores
Lucía
L
Vázquez
Carmen M
CM
Planas
Joana M
JM
D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D007082:Ileum / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D051269:Sodium-Glucose Transporter 1 / Q000378:metabolism*
D012333:RNA, Messenger; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D005947:Glucose