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Table of Contents   
ORIGINAL RESEARCH  
Year : 2012  |  Volume : 23  |  Issue : 5  |  Page : 565-567
Immuno-localization of glucose transporter 4 in healthy human gingiva


1 Department of Periodontics, Faculty of Dental Sciences, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra University, Chennai, India
2 Department of Pathology, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra University, Chennai, India

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Date of Submission26-May-2011
Date of Decision25-Nov-2011
Date of Acceptance12-Feb-2012
Date of Web Publication19-Feb-2013
 

   Abstract 

Background: The gingiva has been shown to be a target tissue for several hormones. Insulin induces uptake of glucose in the peripheral tissues by upregulating the Glucose transporter 4 expression. Little information is available on the expression of Glucose transporter 4 in human gingiva.
Aim: In this regard, a pilot study was performed with the aim of determining the distribution pattern of Glucose transporter 4 in healthy human gingiva.
Materials and Methods: Immuno-histochemistry was performed on 10 mounted sections of healthy human gingiva with the primary antibody Glucose Transporter 4 (GLUT 4). Appropriate positive and negative controls were used.
Results: Glucose transporter 4 expression was observed in the basal and suprabasal layers of the gingival epithelium and fibroblasts of the gingival connective tissue.
Conclusion: This may be the first study to demonstrate the expression of GLUT 4 in the healthy human gingiva. The results of this study raise the possibility that gingiva may serve as a target tissue for insulin action.

Keywords: Glucose metabolism, glucose transporter 4, human gingiva

How to cite this article:
Rao SR, Sundaram S, Lavu V. Immuno-localization of glucose transporter 4 in healthy human gingiva. Indian J Dent Res 2012;23:565-7

How to cite this URL:
Rao SR, Sundaram S, Lavu V. Immuno-localization of glucose transporter 4 in healthy human gingiva. Indian J Dent Res [serial online] 2012 [cited 2020 Aug 6];23:565-7. Available from: http://www.ijdr.in/text.asp?2012/23/5/565/107327
The primary source of glucose, the fundamental source of energy for all living beings, is obtained from the dietary intake of various sugars. It is then absorbed into the circulation and carried to the different organs of the human body for the purpose of utilization and storage. Glucose transport into a cell is mediated through active and passive means. The passive transport is facilitated through a family of Glucose transporters called the GLUT family. The distribution of the GLUT family members is unique with specific functions assigned to each member. GLUT -4 is an insulin sensitive isoform that is primarily expressed in the adipose tissue and skeletal muscles. In contrast, the other GLUT isoforms are primarily localized to the cell membrane and GLUT-4 is sequestered intra-cellularly in specialized storage vesicles. As post prandial glucose levels rise, the subsequent increase in circulating insulin activate the intracellular signaling cascades that culminate in GLUT-4 translocation to the cell membrane. The cells of the periodontium as in other parts of the body are dependent on glucose for their metabolic activity. The mechanism involved in glucose uptake by these cells has not received much attention. Several studies have shown the influence of chronic periodontitis on diabetes mellitus type II and vice versa, leading to some authors quoting this as a two way phenomenon. [1] Although clinical [2] and epidemiological studies [3] have been done supporting this bi- directional relationship, the underlying mechanisms which influence the insulin deficiency/ resistance (seen in Type I/ Type II diabetes mellitus respectively) on the cells of the periodontium remain to be determined. In this regard, we performed a pilot study to identify the presence and localize GLUT-4 in the cells of healthy human gingiva as an initial step in determining the effects of insulin action. With the above background information, we conducted a study to identify the presence of GLUT-4 in healthy human gingiva by use of the immunohistochemistry technique.


   Materials and Methods Top


A total of 10 subjects with healthy human gingiva were recruited for this study. The healthy gingival samples were collected from the patients visiting the Out-Patient Department of Oral surgery, Sri Ramachandra Dental College, Sri Ramachandra University for the purpose of extraction of teeth for orthodontic purposes. Ethical approval was obtained from the Institutional Ethics Committee, Sri Ramachandra University. Informed consent was obtained from each patient prior to the sample collection. The samples were fixed in 4% buffered formalin and embedded in paraffin, and immunohistochemistry was performed in 5 micron sections using the polyclonal antibody to GLUT-4 (Chemicon International) in a 1:100 dilution, and a Universal Secondary kit (LSAB from Dako cytomation). The positive control samples included sections of skeletal muscle and adipose tissue. The negative control tissue was a section of the lung tissue. The positive and negative control samples were obtained from the Department of General Pathology, Sri Ramachandra University. The staining was considered positive if a peri-nuclear staining was observed.


   Results Top


A peri-nuclear staining was observed in the cells of both the gingival epithelium and the connective tissue [Figure 1]. In the gingival epithelium, the basal layer demonstrated a higher staining intensity as compared to the superficial layers [Figure 2]. The peri-nuclear staining pattern was also observed in fibroblasts of the sub-epithelial connective tissue layer. All the ten samples and positive controls [Figure 3] and [Figure 4] demonstrated the staining pattern. The lung tissue sections (negative control) [Figure 5] did not demonstrate any staining.
Figure 1: Photomicrograph of section of healthy human gingiva showing peri-nuclear staining of the cells of the epithelium and the connective tissue. The basal layer shows a stronger (+++) staining as compared to the superficial layers (+) at ×40 magnification

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Figure 2: Photomicrograph of healthy human gingiva showing at ×100 magnification; the perinuclear staining of the basal and parabasal cells of the gingival epithelium

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Figure 3: Photomicrograph of section of skeletal muscle (Positive control) with positive staining for Glucose transporter 4 at ×40 magnification

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Figure 4: Photomicrograph of section of adipose tissue (Positive control) with positive staining for Glucose transporter 4 at 40×magnification

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Figure 5: Photomicrograph of section of the lung tissue (negative control) showing negativity for Glucose transporter 4 at 40×magnification

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   Discussion Top


To our knowledge, this is the first report on identification on GLUT-4 in human gingiva. The periodontium has been shown to be a target tissue for many hormones (estrogen, progesterone, glucocorticoids, etc). Receptors for the hormones - estrogen,[4] progesterone,[5] testosterone,[6] glucocorticoids[7] have been identified in the gingiva. The insulin mediated glucose uptake by target cells such as adipocytes and cardiac muscle cells is mediated through the GLUT-4 transporter. GLUT-4 has been previously localized in the above mentioned target tissue. However, a recent report by Ericsson A et al. 2005 [8] demonstrated the expression of GLUT-4 in the syncytiotrophoblast of the first trimester of the human placenta. The above discovery has thrown open the possibility of GLUT-4 expression being present in several different tissues. The significance of the results of our study should be viewed in light of the fact that glucose metabolism in the gingiva primarily occurs by aerobic glycolysis. The gingiva is a highly vascular tissue and the cells of both the connective tissue and the basal layer of the gingival epithelium demonstrate a high rate of aerobic glycolysis. However, the cells of the superficial layer of the epithelium demonstrate a lower metabolic activity and reduced oxygen utilization. In this layer of cells, an alternate pathway of glucose metabolism (hexose monophosphate pathway) has been shown to be effective. This pathway is believed to play a role in the formation of ribonucleoproteins which represents an essential step in the changes occurring as a part of the keratinization process. In the past, aerobic glycolysis occurring in the gingiva has been studied in experimental animals by the use of the enzyme histochemistry technique.

Bergquist J,[9] studied the distribution of lactate dehydrogenase in the gingiva of dogs and found the activity to be highest in the basal layer of the gingival epithelium, and found it to be progressively decreased towards the superficial layers of the epithelium. Another study by Itoiz ME et al. [10] reported that the activity of glucose 6 phosphate dehydrogenase (a key enzyme involved in the hexose monophosphate pathway) increased progressively from the basal to the superficial layers, whereas succinic dehydrogenase (enzyme involved in aerobic glycolysis) activity reduced from the basal layer to the surface. From the above data, we conclude that the gingiva is a possible target tissue for insulin and the GLUT-4 expression pattern observed in this study co-relates with the glycolytic pathways existing in the gingival epithelium. Insulin stimulates glucose uptake by the cells and this is primarily mediated by the GLUT 4.

The findings of this pilot study therefore provide an insight into the mechanisms involved in the insulin action on the cells of the gingiva. However, the limitation of this study, lies in the fact that, further work needs to be done for more conclusive evidence. Insulin receptor expression on the cells of the gingiva needs to be demonstrated, and the intracellular pathway involved in the cell surface expression of GLUT 4 following the stimulation of the gingival fibroblasts and the epithelial cells with insulin needs to be elucidated.

 
   References Top

1.Grossi SG, Genco RJ. Periodontal disease and Diabetes Mellitus: A Two Way Relationship. Ann Periodontol 1998;3:51-61.  Back to cited text no. 1
[PUBMED]    
2.Tervonen T, Knuttila M, Pohjamo L, Nurkkala H. Immediate response to nonsurgicalperiodontal treatment in subjects with diabetes mellitus. J Clin Periodontol 1991;18:65-8.  Back to cited text no. 2
    
3.Taylor GW, Burt BA, Becker MP, Genco RJ, Shlossman M, Knowler WC, et al. Severe periodontitis and risk for poor glycemic control in patients with non-insulin dependent diabetes mellitus. J Periodontol 1996;67: 1085-93.  Back to cited text no. 3
[PUBMED]    
4.Vittek J, Hernandez MR, Wenk EJ, Rappaport SC, Southren AL. Specific estrogen receptors in human gingiva. J Clin Endocrinol Metab 1982;54:608-12.  Back to cited text no. 4
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5.Vittek J, Gordon GG, Rappaport SC, Munnangi PR, Southren AL. Specific progesterone receptors in rabbit gingiva. J Periodontal Res 1982;17:657-61.  Back to cited text no. 5
[PUBMED]    
6.Southren AL, Rappaport SC, Gordon GG, Vittek J. Specific 5 alphadihydrotestosterone receptors in human gingiva. J Clin Endocrinol Metab 1978;47:1378-82.  Back to cited text no. 6
[PUBMED]    
7.Suresh R, Dhar SC. Glucorticoid receptors in human gingiva. Biochem Int 1991;23:383-8.  Back to cited text no. 7
[PUBMED]    
8.Ericsson A, Hamark B, Powell TL, Jansson T. Glucose transporter isoform 4 is expressed in the syncytiotrophoblast of first trimester human placenta. Hum Reprod 2005;20:521-30.  Back to cited text no. 8
[PUBMED]    
9.Bergquist JJ. Lactate dehydrogenase in non-inflamed attached gingiva of dogs. J Periodontol Res 1972a;7:8-13.  Back to cited text no. 9
    
10.Itoiz ME, Carranza FA Jr, Giminez IG, Cabrini RL. Microspectrophotometric analysis of succinic dehydrogenase and glucose-6-phosphate dehydrogenase in human oral epithelium. J Periodontal Res 1972;7:14-20.  Back to cited text no. 10
    

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Correspondence Address:
Suresh Ranga Rao
Department of Periodontics, Faculty of Dental Sciences, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra University, Chennai
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-9290.107327

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

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