Advertisement

Molecular Biology Reports

, Volume 46, Issue 2, pp 2273–2283 | Cite as

Fractionated whole body gamma irradiation modulates the hepatic response in type II diabetes of high fat diet model rats

  • Ayman KhalilEmail author
  • Antonious Al-Daoude
Original Article
  • 92 Downloads

Abstract

HFD animals were exposed to a low rate of different fractionated whole body gamma irradiation doses (0.5, 1 and 2 Gy, three fractions per week for two consecutive months) and the expression of certain genes involved in type 2 diabetes mellitus (T2DM) in livers and brains of HFD Wistar rats was investigated. Additionally, levels of diabetes-related proteins encoded by the studied genes were analyzed. Results indicated that mRNA level of incretin glucagon like peptite-1 receptor (GLP-1R) was augmented in livers and brains exposed to 1 and 2 Gy doses. Moreover, the mitochondrial uncoupling proteins 2 and 3 (UCP2/3) expressions in animals fed on HFD compared to those fed on normal chow diet were significantly increased at all applied doses. GLP-1R and UCP3 protein levels were up regulated in livers. Total protein content increased at 0.5 and 1 Gy gamma irradiation exposure and returned to its normal level at 2 Gy dose. Results could be an indicator of type 2 diabetes delayed development during irradiation exposure and support the importance of GLP-1R as a target gene in radiotherapy against T2DM and its chronic complications. A new hypothesis of brain-liver and intestine interface is speculated by which an increase in the hepatic GLP-1R is influenced by the effect of fractionated whole body gamma irradiation.

Keywords

Fractionated whole body gamma irradiation (FWBGI) Liver Type 2 diabetes GLP-1 GLP-1R HFD 

Notes

Acknowledgements

The authors wish to express their deep appreciation to Prof. Ibrahim Othman, the director general of the Atomic Energy Commission of Syria (AECS). Thanks are also extended to Dr. M. A. Bakir, the head of the radiation medicine department for his help and support throughout the period of this research and to Dr. K. Aljoumaa for his appreciated scientific advices.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All institutional and national guidelines for the care and use of laboratory animals were obeyed by the Local Scientific and Ethical Committee of the Atomic Energy Commission of Syria (AECS), Damascus, Syria (permit number is 2-28/10/2018). This article does not contain any studies with human participants performed by any of the authors.

References

  1. 1.
    Seymour J, Clark D, Winslow M (2005) Pain and palliative care. The emergence of new specialties. J Pain Symptom Manage 29:2–13CrossRefPubMedGoogle Scholar
  2. 2.
    Wan X-S, Ware J-H, Zhou Z et al (2006) Protection against radiation-induced oxidative stress in cultured human epithelial cells by treatment with antioxidant agents. Int J Radiat Oncol Biol Phys 64:1475–1481CrossRefPubMedGoogle Scholar
  3. 3.
    Preston DL, Shimizu Y, Pierce DA, Suyama A, Mabuchi K (2003) Studies of mortality of atomic bomb survivors. Report 13: solid cancer and noncancer disease mortality: 1950–1997. Radiat Res 160:381–407CrossRefPubMedGoogle Scholar
  4. 4.
    Yamada M, Wong FL, Fujiwara S, Akahoshi M, Suzuki G (2004) Noncancer disease incidence in atomic bomb survivors, 1958–1998. Radiat Res 161:622–632CrossRefPubMedGoogle Scholar
  5. 5.
    Panes J, Granger DN (1998) Leukocyte-endothelial cell interactions: molecular mechanisms and implications in gastrointestinal disease. Gastroenterology 114:1066–1090CrossRefPubMedGoogle Scholar
  6. 6.
    Stone HB, Coleman CN, Anscher MS, McBride WH (2003) Effects of radiation on normal tissue: consequences and mechanisms. Lancet Oncol 4:529–536CrossRefPubMedGoogle Scholar
  7. 7.
    Zalutskaya A, Bornstein SR, Mokhort T, Garmaev D (2004) Did the Chernobyl incident cause an increase in type 1 diabetes mellitus incidence in children and adolescents? Diabetologia 47:147–148CrossRefPubMedGoogle Scholar
  8. 8.
    Kavanagh K, Dendinger MD, Davis AT, Register TC, DeBo R, Dugan G, Cline JM (2015) Type 2 diabetes is a delayed late effect of whole-body irradiation in nonhuman primates. Radiat Res 183:398–406CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Supic G, Jagodic M, Magic Z (2013) Epigenetics: a new link between nutrition and cancer. Nutr Cancer 65:781–792CrossRefPubMedGoogle Scholar
  10. 10.
    Vares G, Wang B, Ishii-Ohba H, Nenoi M, Nakajima T (2014) Diet-induced obesity modulates epigenetic responses to ionizing radiation in mice. PLoS ONE 9:e106277CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Nylander V, Ingerslev LR, Andersen E, Fabre O, Garde C, Rasmussen M, Citirikkaya K, Bæk J, Christensen GL, Aznar M, Specht L, Simar D, Barrès R (2016) Ionizing radiation potentiates high-fat diet-induced Insulin resistance and reprograms skeletal muscle and adipose progenitor cells. Diabetes 65:3573–3584CrossRefPubMedGoogle Scholar
  12. 12.
    Rossmeisl M, Rim JS, Koza RA, Kozak LP (2003) Variation in type 2 diabetes-related traits in mouse strains susceptible to diet-induced obesity. Diabetes 52:1958–1966CrossRefPubMedGoogle Scholar
  13. 13.
    Deji N, Kume S, Araki S-i, Soumura M, Sugimoto T, Isshiki K et al (2009) Structural and functional changes in the kidneys of high-fat diet-induced obese mice. Am J Physiol Renal Physiol 296:F118–F126CrossRefPubMedGoogle Scholar
  14. 14.
    Nakamura A, Terauchi Y (2013) Lessons from mouse models of high-fat diet-induced NAFLD. Int J Mol Sci 14:21240–21257CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Maitra A, Abbas AK (2015) Endocrine system. Robbins and cotran pathologic basis of disease, 7th edn. Saunders, Philadelphia, pp 1156–1226Google Scholar
  16. 16.
    Carvalho E, Jansson PA, Axelsen M, Eriksson JW, Huang X, Groop L, Rondinone C, Sjostrom L, Smith U (1999) Low cellular IRS 1 gene and protein expression predict insulin resistance and NIDDM. FASEB J 13:2173–2178CrossRefPubMedGoogle Scholar
  17. 17.
    Shaw LM (2011) The insulin receptor substrate (IRS) proteins: at the intersection of metabolism and cancer. Cell Cycle 10:1750–1756CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Choi WH, O’Rahilly S, Buse JB, Rees A, Morgan R, Flier JS, Moller DE (1991) Molecular scanning of the insulin-responsive glucose transporter (GLUT4) gene in NIDDM subjects. Diabetes 40:1712–1718CrossRefPubMedGoogle Scholar
  19. 19.
    Krook A, Digby J, O’Rahilly S, Zierath JR, Wallberg-Henriksson H (1998) Uncoupling protein 3 is reduced in skeletal muscle of NIDDM patients. Diabetes 47:1528–1531CrossRefPubMedGoogle Scholar
  20. 20.
    Schrauwen P, Hesselink MK (2004) Oxidative capacity, lipotoxicity, and mitochondrial damage in type 2 diabetes. Diabetes 53:1412–1417CrossRefPubMedGoogle Scholar
  21. 21.
    vanVliet-Ostaptchouk JV, van Haeften TW, Landman GW, Reiling E, Kleefstra N, Bilo HJ, Klungel OH et al (2012) Common variants in the type 2 diabetes KCNQ1 gene are associated with impairments in insulin secretion during hyperglycemic glucose clamp. PLoS ONE 7:e32148CrossRefGoogle Scholar
  22. 22.
    Holmkvist J, Banasik K, Andersen G, Unoki H, Jensen TS, Pisinger C et al (2009) The type 2 diabetes associated minor allele of rs2237895 KCNQ1 associates with reduced insulin release following an oral glucose load. PLoS ONE 4:e5872CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    MacDonald PE, Wheeler MB (2003) Voltage-dependent K(+) channels in pancreatic beta cells: role, regulation and potential as therapeutic targets. Diabetologia 46:1046–1062CrossRefPubMedGoogle Scholar
  24. 24.
    Sokolova EA, Irina AB, Olesya YS, Olga VP, Maxim LF (2015) Replication of KCNJ11 (p.E23K) and ABCC8 (p.S1369A) Association in Russian Diabetes Mellitus 2 Type Cohort and Meta-Analysis. PLoS ONE 10:e0124662CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Miki T, Nagashima K, Seino S (1999) The structure and function of the ATP-sensitive K+ channel in insulin-secreting pancreatic beta-cells. J Mol Endocrinol 22:113–123CrossRefPubMedGoogle Scholar
  26. 26.
    Wang G-J, Li X-K, Sakai K, Cai L (2008) Low-dose radiation and its clinical implications: diabetes. Hum Exp Toxicol 27:135–142CrossRefPubMedGoogle Scholar
  27. 27.
    Auberval N, Dal S, Bietiger W et al (2014) Metabolic and oxidative stress markers in Wistar rats after 2 months on a high-fat diet. Diabetol Metab Syndr 6:130CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Leduc‐Gaudet JP, Reynaud O, Chabot F, Mercier J, Andrich DE, St‐Pierre DH, Gouspillou G (2018) The impact of a short-term high-fat diet on mitochondrial respiration, reactive oxygen species production, and dynamics in oxidative and glycolytic skeletal muscles of young rats. Physiol Rep 6(4):e13548CrossRefPubMedCentralGoogle Scholar
  29. 29.
    Blackshaw JK, Fenwick CC, Beattie AW, Allan DJ (1988) The behaviour of chickens, mice and rats during euthanasia with chloroform, carbon dioxide and ether. Lab Anim 22:67–75CrossRefPubMedGoogle Scholar
  30. 30.
    Schmittgen TD, Livak JL (2008) Analyzing real-time PCR data by the comparative Ct method. Nat Protoc 3:1101–1108CrossRefGoogle Scholar
  31. 31.
    Wang C, Zhang T, Cui X et al (2013) Hepatoprotective effects of a Chinese herbal formula, longyin decoction, on carbon-tetrachloride-induced liver injury in chickens. Evid-Based Complement Alterna Med 2013: 392743Google Scholar
  32. 32.
    Khalil A, Villard PH, Dao MA, Burcelin R, Champion S, Fouchier F, Savouret JF, Barra Y, Seree E (2010) Polycyclic aromatic hydrocarbons potentiate high-fat diet effects on intestinal inflammation. Toxicol Lett 196:161–167CrossRefPubMedGoogle Scholar
  33. 33.
    Yoshida S, Tanaka H, Oshima H, Yamazaki T, Yonetoku Y, Ohishi T, Matsui T, Shibasaki M (2010) A novel GPR119 agonist, as an insulinotropic and β-cell preservative agent for the treatment of type 2 diabetes. Biochem Biophys Res Commun 400:745–751CrossRefPubMedGoogle Scholar
  34. 34.
    Gault VA, Kerr BD, Harriott P, Flatt PR (2011) Administration of an acylated GLP-1 and GIP preparation provides added beneficial glucose-lowering and insulinotropic actions over single incretins in mice with Type 2 diabetes and obesity. Clin Sci (Lond) 121:107–117CrossRefGoogle Scholar
  35. 35.
    Park JS, Rhee SD, Kang NS, Jung WH, Kim HY, Kim JH, Kang SK, Cheon HG, Ahn JH, Kim KY (2011) Anti-diabetic and anti-adipogenic effects of a novel selective 11β hydroxysteroid dehydrogenase type 1 inhibitor, 2-(3-benzoyl)-4-hydroxy-1, 1-dioxo-2H-1, 2-benzothiazine-2-yl-1-phenylethanone (KR-66344). Biochem Pharmacol 81:1028–1035CrossRefPubMedGoogle Scholar
  36. 36.
    Suman RK, Ray M, Borde MK, Maheshwari U, Deshmukh YA (2016) Development of an experimental model of diabetes co-existing with metabolic syndrome in rats. Adv Pharmacol Sci 2016: 9463476PubMedPubMedCentralGoogle Scholar
  37. 37.
    Obrosova IG, Ilnytska O, Lyzogubov VV, Pavlov IA, Mashtalir N, Nadler JL, Drel VR (2007) High-fat diet induced neuropathy of pre-diabetes and obesity: effects of “healthy” diet and aldose reductase inhibition. Diabetes 56:2598–2608CrossRefPubMedGoogle Scholar
  38. 38.
    Moroz N, Tong M, Longato L, Xu H, de la Monte SM (2008) Limited Alzheimer-type neurodegeneration in experimental obesity and type 2 diabetes mellitus. J Alzheimers Dis 15:29–44CrossRefPubMedGoogle Scholar
  39. 39.
    Unoki H, Takahashi A, Kawaguchi T, Hara K, Horikoshi M, Andersen G, Ng DP, Holmkvist J et al (2008) SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nat Genet 40:1098–1102CrossRefPubMedGoogle Scholar
  40. 40.
    Yasuda K, Miyake K, Horikawa Y, Hara K, Osawa H, Furuta H, Hirota Y, Mori H, Jonsson A, Sato Y, Yamagata K, Hinokio Y et al (2008) Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat Genet 40:1092–1097CrossRefPubMedGoogle Scholar
  41. 41.
    Hamming KSC, Soliman D, Matemisz LC, Niazi O, Lang Y, Gloyn L, Light PE (2008) Coexpression of the Type 2 diabetes susceptibility gene variants KCNJ11 E23K and ABCC8 S1369A alter the ATP and sulfonylurea sensitivities of the ATP-sensitive K+ channel. Diabetes 58:2419–2424CrossRefGoogle Scholar
  42. 42.
    Nomura T, Li XH, Ogata H, Sakai K, Kondo T, Takano Y, Magae J (2011) Suppressive effects of continuous low-dose-rate γ irradiation on diabetic nephropathy in type II diabetes mellitus model mice. Radiat Res 176:356–365CrossRefPubMedGoogle Scholar
  43. 43.
    Tsuruzoe K, Emkey R, Kriauciunas KM, Ueki K, Kahn CR (2001) Insulin receptor substrate 3 (IRS-3) and IRS-4 impair IRS-1- and IRS-2-mediated signaling. Mol Cell Biol 21:26–38CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Cai L (1999) Research of the adaptive response induced by low-dose radiation. Where have we been and where should we go? Hum Exp Toxicol 18:419–425CrossRefPubMedGoogle Scholar
  45. 45.
    Calabrese EJ (2002) Hormesis: Changing view of the dose response, a personal account of the history and current status. Mutat Res 511:181–189CrossRefPubMedGoogle Scholar
  46. 46.
    Calabrese EJ, Baldwin LA (2003) Hormesis: the dose response revolution. Annu Rev Pharmacol Toxicol 43:175–197CrossRefPubMedGoogle Scholar
  47. 47.
    Shao M, Lu X, Cong W, Xing X, Tan Y et al (2014) Multiple low-dose radiation prevents type 2 diabetes-induced renal damage through attenuation of Dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress. PLoS ONE 9:e92574CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Khalil A, Omran H (2018) The role of gut in type 2 diabetes mellitus during whole body gamma irradiation in high-fat diet Wistar rats. Int J Radiat Biol 94:137–149CrossRefPubMedGoogle Scholar
  49. 49.
    Fisler J, Warden CH (2006) Uncoupling proteins, dietary fat and the metabolic syndrome. Nutr Metab (Lond) 3:38CrossRefGoogle Scholar
  50. 50.
    Esteves T, Brand M (2005) The reactions catalysed by the mitochondrial uncoupling proteins UCP2 and UCP3. Biochim Biophys Acta 1709:35–44CrossRefPubMedGoogle Scholar
  51. 51.
    Cui Y, Xu X, Bi H, Zhu Q, Wu J, Xia X et al (2006) Expression modification of uncoupling proteins and MnSOD in retinal endothelial cells and pericytes induced by high glucose. The role of reactive oxygen species in diabetic retinopathy. Exp Eye Res 83:807–816CrossRefPubMedGoogle Scholar
  52. 52.
    Matsuda J, Hosoda K, Itoh H, Son C, Doi K, Tanaka T, Fukunaga Y, Inoue G, Nishimura H, Yoshimasa Y, Yamori Y, Nakao K (1997) Cloning of rat uncoupling protein-3 and uncoupling protein-2 cDNAs. Their gene expression in rats fed high-fat diet. FEBS Lett 418:200–204CrossRefPubMedGoogle Scholar
  53. 53.
    Camara Y, Mampel T, Armengol J, Villarroya F, Dejean L (2009) UCP3 expression in liver modulates gene expression and oxidative metabolism in response to fatty acids, and sensitizes mitochondria to permeability transition. Cell Physiol Biochem 24:243–252CrossRefPubMedGoogle Scholar
  54. 54.
    Khalil A, Omran H, Alsheikh F (2018) Balance of pro- and anti-inflammatory cytokines in livers of high fat diet rats exposed to fractionated gamma irradiation. BMC Res Notes 11:741CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Radiation Medicine, Human Nutrition LaboratoryAtomic Energy Commission of Syria (AECS)DamascusSyria
  2. 2.Department of Molecular Biology and BiotechnologyAECSDamascusSyria

Personalised recommendations