Naslov
TISSUE EXPRESSION PROFILING OF THE MOUSE Sglt1 mRNA AND PROTEIN WITH SEX-DEPENDENT Sglt1 RENAL EXPRESSION

Autori
Vrhovac, Ivana ; Breljak, Davorka ; Karaica, Dean ; Koepsell Hermann ; Sabolić, Ivan

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
The Interplay of Biomolecules / Katalinic, M ; Kovarik, Z - Zagreb : Hrvatsko Društvo za Biotehnologiju, 2014, 79-79

ISBN
978-953-95551-5-1

Skup
Congress of The Croatian Society of Biochemistry and Molecular Biology: The Interplay of Biomolecules

Mjesto i datum
Zadar, Hrvatska, 24.09.2014. - 27.09.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
glucose transport ; Sglt1 ; kidney ; mouse ; sex differences

Sažetak
One of the diseases in humans, with most growing incidence, is diabetes mellitus type 2, which is characterized by hyperglycemia and various successive complications. Novel antidiabetic drugs have been proposed that would inhibit the activity of SGLT1 (SLC5A1 in humans)/Sglt1 (Slc5a1 in rodents) in the brush-border membrane (BBM) of small intestinal enterocytes and renal proximal tubules (PT), and would impair absorption and reabsorption, respectively, of glucose in these organs. The impact of such drugs on other organs is unknown, since the expression of SGLT1 in other organs/tissues has been poorly studied, or is contradictory. Since mice are frequently used in preclinical studies, knowledge of the Sglt1 distribution in various mouse organs/tissues as possible targets for such drugs would be of great importance. In order to determine the Sglt1 mRNA and protein expression by qPCR, Western blotting (WB) and immunocytochemistry (IC), we compared these parameters in various organs/tissues of wild-type (WT) and Sglt1 knockout (KO) mice. By qPCR: a) highest expression of Sglt1 mRNA was observed in the small intestine, b) high expression was measured in seminal vesicles, kidneys, salivary glands (parotid, submandibular and sublingual), and prostate, c) medium expression was observed in eyes, tongue, pancreas, lungs, and liver, and d) low expression was found in skeletal muscle, testes, heart, fat, epididymis, cerebellum, cerebrum, and spleen. Cell localization of the Sglt1 protein was studied by WB and IC in the Sglt1 mRNA positive tissues using the antibody whose specificity was confirmed in Sglt1 KO mice. By IC, in the kidneys of WT mice, Sglt1 protein was localized to the BBM of PT and luminal membrane of TALH, exhibiting segmental (S2>S3), zonal (cortex>outer stripe), and sex (males (M)>females (F)) differences. In the small intestine, liver and pancreas, it was localized to the BBM of enterocytes, bile ducts and pancreatic ducts, respectively. By WB, a single Sglt1-related protein band of 75 kDa was detected in the BBM of kidneys and small intestine. The Sglt1-related staining and protein bands were not observed in the respective organs of Sglt1 KO mice. Contrary to the M-dominant Sglt1 protein expression, the renal Sglt1 mRNA expression was F-dominant. Our data show that Sglt1 is expressed in various organs/tissues, and thus indicate that the potential inhibitors of SGLT1 activity may target various organs/tissues with unpredictable consequences.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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