The online version of this article (doi:10.1186/1758-5996-6-97) contains supplementary material, which is available to authorized users.
All authors declare that they have no competing interests.
Hypertension has been associated to diabetes, and participates in the development of diabetic complications. The spontaneously hypertensive rat (SHR) is the gold standard model for the study of hypertension, and experimental diabetes has been currently investigated in SHR. Wistar-Kyoto rat is usually taken as control for SHR, however, regarding the glycemic homeostasis, WKY may be similar to SHR, when compared to the standard Wistar rat, importantly affecting the interpretation of data. Slc2a4 gene, which encodes the GLUT4 protein, is expressed in insulin-sensitive tissues, such as muscle cells and adipocytes, and alteration in Slc2a4/GLUT4 expression is inversely related to glycemic levels. We investigated the effect of diabetes on the expression of Slc2a4/GLUT4 and glycemic control in Wistar-Kyoto and SHR.
Slc2a4 mRNA (Northern-blotting) and GLUT4 protein (Western-blotting) were investigated in skeletal muscles (soleus and extensor digitorum longus) of Wistar, Wistar-Kyoto and SHR, rendered or not diabetic for 1 month. Non-diabetic SHR shows hyperinsulinemia, and unaltered GLUT4 expression. The hyperglycemia was significantly attenuated in diabetic Wistar-Kyoto and SHR, compared to that observed in diabetic Wistar, although all of them presented the same hypoinsulinemic levels. Besides, diabetes significantly reduced Slc2a4/GLUT4 in Wistar, as expected; however, that was not observed in diabetic Wistar-Kyoto and SHR.
Non-diabetic SHR is insulin resistant, despite unaltered GLUT4 expression. Diabetic Wistar-Kyoto and diabetic SHR presented high Slc2a4/GLUT4 expression in skeletal muscle, as compared to diabetic Wistar. This Slc2a4/GLUT4 regulation does not depend on insulin level and possibly protects the WKY and SHR from severe glycemic impairment.
Authors’ original file for figure 113098_2014_358_MOESM1_ESM.pdf
Reaven GM: The metabolic syndrome: is this diagnosis necessary?. Am J Clin Nutr. 2006, 83: 1237-1247. PubMed
Schaan BD, Irigoyen MC, Bertoluci MC, Lima NG, Passaglia J, Hermes E, Oliveira FR, Okamoto M, Machado UF: Increased urinary TGF-beta1 and cortical renal GLUT1 and GLUT2 levels: additive effects of hypertension and diabetes. Nephron Physiol. 2005, 100 (3): 43-50. 10.1159/000085413. CrossRef
Sabino-Silva R, Alves-Wagner ABT, Burgi K, Okamoto MM, Alves AS, Lima GA, Freitas HS, Antunes VR, Machado UF: SGLT1 protein expression in plasma membrane of acinar cells correlates with the sympathetic outflow to salivary glands in diabetic and hypertensive rats. Am J Physiol Endocrinol Metab. 2010, 299 (6): E1028-E1037. 10.1152/ajpendo.00395.2010. CrossRefPubMed
Vestri S, Okamoto MM, Freitas HS, Aparecida dos Santos R, Nunes MT, Morimatsu M, Heimann JC, Machado UF: Changes in sodium or glucose filtration rate modulate expression of glucose transporters in renal proximal tubular cells of rat. J Membr Biol. 2001, 182: 105-112. 10.1007/s00232-001-0036-y. CrossRefPubMed
Freitas HS, Anhê GF, Melo KF, Okamoto MM, Oliveira-Souza M, Bordin S, Machado UF: Na(+) -glucose transporter-2 messenger ribonucleic acid expression in kidney of diabetic rats correlates with glycemic levels: involvement of hepatocyte nuclear factor-1alpha expression and activity. Endocrinology. 2008, 149 (2): 717-724. 10.1210/en.2007-1088. CrossRefPubMed
Okamoto MM, Anhê GF, Sabino-Silva R, Marques MF, Freitas HS, Mori RC, Melo KF, Machado UF: Intensive insulin treatment induces insulin resistance in diabetic rats by imparing glucose metabolism-related mechanisms in muscle and liver. J Endocrinol. 2011, 211 (1): 55-64. 10.1530/JOE-11-0105. CrossRefPubMed
Baron AD, Brechtel G, Wallace P, Edelman SV: Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans. Am J Physiol. 1988, 255 (6 Pt 1): E769-E774. PubMed
Zecchin HG, Bezerra RM, Carvalheira JB, Carvalho-Filho MA, Metze K, Franchini KG, Saad MJ: Insulin signaling pathways in aorta and muscle from two animal models of insulin resistance - the obese middle-aged and the spontaneously hypertensive rats. Diabetologia. 2003, 46 (4): 479-491. PubMed
- Decreased diabetes-induced glycemic impairment in WKY and SHR involves enhanced skeletal muscle Slc2a4/GLUT4 expression
Ana Barbara Alves-Wagner
Raquel S Campello
Rosana C Mori
Ubiratan F Machado
- BioMed Central
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