THE ROLE OF SURVIVIN AND RAF-1 KINASE AGAINST ENHANCEMENT OF PANCREATIC BETA-CELL APOPTOSIS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Eva Decroli; Asman Manaf; Syafril Syahbuddin; Sarwono Waspadji; Dwisari Dillasamola

doi:10.22159/ajpcr.2018.v11i11.27671

Authors

Eva Decroli Endocrinology and Metabolic Subdivision, Division of Internal Medicine, Dr. M. Djamil General Hospital/Medical Faculty, Andalas University, Padang, Indonesia.
Asman Manaf Endocrinology and Metabolic Subdivision, Division of Internal Medicine, Dr. M. Djamil General Hospital/Medical Faculty, Andalas University, Padang, Indonesia.
Syafril Syahbuddin Endocrinology and Metabolic Subdivision, Division of Internal Medicine, Dr. M. Djamil General Hospital/Medical Faculty, Andalas University, Padang, Indonesia.
Sarwono Waspadji Endocrinology and Metabolic Subdivision, Division of Internal Medicine, Medical Faculty, Indonesia University, Jakarta, Indonesia.
Dwisari Dillasamola Department of Medicine, Division of Endocrinology and Metabolism, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.

DOI:

https://doi.org/10.22159/ajpcr.2018.v11i11.27671

Keywords:

Survivin, Raf-1 kinase, Hemoglobin A1c, Type 2 diabetes mellitus

Abstract

Objective: This study aimed to reveal differences in levels of survivin and Raf-1 kinase in prediabetes, controlled Type 2 diabetes mellitus (T2DM), uncontrolled T2DM, and their relationship with hemoglobin A1c (HbA1c) levels and serum triglyceride levels.

Methods: This study was an observational study with a cross-sectional design. The study involved 60 people with T2DM who visited the endocrine and metabolic clinic and 30 prediabetes patients. The variables were survivin levels and Raf-1 kinase enzymes that examined using enzyme-linked immunosorbent assay techniques. HbA1c values are measured by high-performance liquid chromatography and triglyceride levels measured by enzymatic method.

Results: Average levels of Raf-1 kinase were significantly higher in the prediabetes group, controlled T2DM, and uncontrolled T2DM (11.6Â±1.4 pg mL, 9.9Â±1.1 pg/mL, and 9.1Â±1.5 pg/mL). Survivin was significantly higher in the prediabetes group, controlled T2DM, and uncontrolled T2DM (5.4Â±0.4 pg mL, 5.0Â±0.2 pg/mL, and 4.7Â±0.1 pg/mL). There was no correlation between HbA1c with Raf-1 kinase levels (R=âˆ’0.215, p=0.250), but there was a correlation between HbA1c with serum survivin levels (R=âˆ’0.6, *p<0.05). There was a correlation between the levels of triglycerides with survivin but not with Raf-1 kinase (R=âˆ’0.267, *p=0.039).

Conclusion: Survivin and Raf-1 kinase levels are lower in uncontrolled T2DM. This explained the role of survivin and Raf-1 kinase against enhancement of pancreatic beta-cell apoptosis in patients with T2DM.

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References

Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047-53.

Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: Pathogenesis and treatment. Lancet 2008;371:2153-6.

Dussa KN, Sahay RK, Ndararajan PM, Hanarao MV. Adaptation of diabetes knowledge questionnaire for South Asian countries context. Int J Pharm Pharm Sci 2017;9:252-6.

Hussain M, Naqvi SB, Khan MA, Rizvi M, Alam S, Abbas A, et al. Direct cost of treatment of diabetes mellitus Type 2 in Pakistan. Int J Pharm Pharm Sci 2014;6:261-4.

Presetiawati I, Andrajati R, Sauriasari R. Effectiveness of a medication booklet and counseling on treatment adherence in Type 2 diabetes mellitus patients. Int J App Pharm 2017;9:27-31.

Dharma S, Macson J, Tobat SR, Dillasamola D. Effect of giving white egg chicken embryo and green beans (Phaseolus radiates) to the histopathology of pancreatic beta-cell from diabetic rats (Rattus novergicus). Res J Pharm Biol Chem Sci 2016;7:2059-67.

Roskoski R Jr. RAF protein-serine/threonine kinases: Structure and regulation. Biochem Biophys Res Commun 2010;399:313-7.

Chiou SK, Jones MK, Tarnawski AS. Survivin-an anti-apoptosis protein: Its biological roles and implications for cancer and beyond. Med Sci Monit 2003;9:PI25-9.

Bacha F, Lee S, Gungor N, Arslanian SA. From pre-diabetes to Type 2 diabetes in obese youth: Pathophysiological characteristics along the spectrum of glucose dysregulation. Diabetes Care 2010;33:2225-31.

Wang H, Gambosova K, Cooper ZA, Holloway MP, Kassai A, Izquierdo D, et al. EGF regulates survivin stability through the Raf-1/ERK pathway in insulin-secreting pancreatic Î²-cells. BMC Mol Biol 2010;11:66.

Bonora E. Protection of pancreatic beta-cells: Is it feasible? Nutr Metab Cardivasc Dis 2008;18:74-83.

Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC, et al. Beta-cell deficit and increased beta-cell apoptosis in humans with Type 2 diabetes. Diabetes 2003;52:102-10.

Marchetti P, Del Prato S, Lupi R, Del Guerra S. The pancreatic beta-cell in human Type 2 diabetes. Nutr Metab Cardiovasc Dis 2006;16 Suppl 1:S3-6.

Wu X, Zhang Q, Wang X, Zhu J, Xu K, Okada H, et al. Survivin is required for beta-cell mass expansion in the pancreatic duct-ligated mouse model. PLoS One 2012;7:e41976.

Beith JL, Alejandro EU, Johnson JD. Insulin stimulates primary beta-cell proliferation via Raf-1 kinase. Endocrinology 2008;149:2251-60.

Ju L, Zhang X, Deng Y, Han J, Yang J, Chen S, et al. Enhanced expression of survivin has distinct roles in adipocyte homeostasis. Cell Death Dis 2017;8:e2533.

Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Oxidative stress and stress-activated signaling pathways: A unifying hypothesis of Type 2 diabetes. Endocr Rev 2002;23:599-622.

Lingohr MK, Buettner R, Rhodes CJ. Pancreatic beta-cell growth and survival â€“ a role in obesity-linked Type 2 diabetes? Trends Mol Med 2002;8:375-84.