Decreased diabetes-induced glycemic impairment in WKY and SHR involves enhanced skeletal muscle Slc2a4/GLUT4 expression

Diabetology & Metabolic Syndrome

Ubiratan F Machado¹  Rosana C Mori¹  Raquel S Campello¹  Robinson Sabino-Silva²  Ana Barbara Alves-Wagner¹ 

[1] Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil;Institute of Biomedical Sciences (ICBIM), Federal University of Uberlandia (UFU), Uberlandia, MG, Brazil

关键词: Hyperglycemia;    Glycemic homeostasis;    EDL;    Soleus;    Hypertension;   

Others  :  1115011
DOI  :  10.1186/1758-5996-6-97

 received in 2014-05-27, accepted in 2014-09-04,  发布年份 2014

【 摘 要 】

Background

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.

Findings

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.

Conclusions

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.

【 授权许可】

   
2014 Alves-Wagner et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Okamoto K, Aoki K: Development of a strain of spontaneously hypertensive rats. Jpn Circ J 1963, 27:282-293.
• [2]Kurtz TW, Morris RC Jr: Biological variability in Wistar-Kyoto rats: Implications for research with the spontaneously hypertensive rat. Hypertension 1987, 10:127-131.
• [3]Katayama S, Inaba M, Maruno Y, Morita T, Awata T, Oka Y: Glucose intolerance in spontaneously hypertensive and Wistar-Kyoto rats: enhanced gene expression and synthesis of skeletal muscle glucose transporter 4. Hypertens Res 1997, 20(4):279-286.
• [4]Aiello EA, Villa-Abrille MC, Escudero EM, Portiansky EL, Pérez NG, Hurtado MCC, Cingolani HE: Myocardial hypertrophy of normotensive Wistar-Kyoto rats. Am J Physiol Heart Circ Physiol 2004, 286(4):H1229-H1235.
• [5]Corrêa-Giannella ML, Machado UF: SLC2A4 gene: a promising target for pharmacogenomics of insulin resistance. Pharmacogenomics 2013, 14(8):847-850.
• [6]Paternostro G, Clarke K, Heath J, Seymour AM, Radda GK: Decreased GLUT-4 mRNA content and insulin-sensitive deoxyglucose uptake show insulin resistance in the hypertensive rat heart. Cardiovasc Res 1995, 30(2):205-211.
• [7]Reaven GM: The metabolic syndrome: is this diagnosis necessary? Am J Clin Nutr 2006, 83:1237-1247.
• [8]UK Prospective Diabetes Study Group: Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998, 317(7160):703-713.
• [9]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]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.
• [11]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.
• [12]Patinha D, Afonso J, Sousa T, Morato M, Albino-Teixeira A: Activation of adenosine receptors improves renal antioxidant status in diabetic Wistar but not SHR rats. Ups J Med Sci 2014, 119:10-18.
• [13]Seraphim PM, Nunes MT, Giannocco G, Machado UF: Age related obesity-induced shortening of GLUT4 mRNA poly(A) tail length in rat gastrocnemius skeletal muscle. Mol Cell Endocrinol 2007, 276(1–2):80-87.
• [14]Alves-Wagner ABT, Freitas HS, Souza PB, Seraphim PM, Mori RCT, Machado UF: β-adrenergic activity preserves GLUT4 protein in glycolytic fibers in fasting. Muscle Nerve 2009, 40(5):847-854.
• [15]Ferguson RE, Carroll HP, Harris A, Maher ER, Selby PJ, Banks RE: Housekeeping proteins: a preliminary study illustrating some limitations as useful references in protein expression studies. Proteomics 2005, 5(2):566-571.
• [16]Papa PC, Seraphim PM, Machado UF: Loss of weight restores GLUT 4 content in insulin-sensitive tissues of monosodium glutamate-treated obese mice. Int J Obes Relat Metab Disord 1997, 21(11):1065-1070.
• [17]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.
• [18]Sabino-Silva R, Freitas HS, Lamers ML, Okamoto MM, Santos MF, Machado UF: Na + -glucose cotransporter SGLT1 protein in salivary glands: potential involvement in the diabetes-induced decrease in salivary flow. J Membr Biol 2009, 228(2):63-69.
• [19]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.
• [20]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.
• [21]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.
• [22]Chiappe De Cingolani GE, Caldiz CI: Insulin resistance and GLUT-4 glucose transporter in adipocytes from hypertensive rats. Metabolism 2004, 53(3):382-387.
• [23]Cabassi A, Vinci S, Cantoni AM, Quartieri F, Maschini L, Cavazzini S, Cavatorta A, Borghetti A: Sympathetic activation in adipose tissue and skeletal muscle of hypertensive rats. Hypertension 2002, 39(2 Pt 2):656-661.
• [24]Mora S, Pessin JE: The MEF2A isoform is required for striated muscle-specific expression of the insulin-responsive GLUT4 glucose transporter. J Biol Chem 2000, 275(21):16323-16328.
• [25]Dimitrakoudis D, Ramlal T, Rastogi S, Vranic M, Klip A: Glycaemia regulates the glucose transporter number in the plasma membrane of rat skeletal muscle. Biochem J 1992, 284(Pt 2):341-348.