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系統識別號 U0026-0812200915242468
論文名稱(中文) 高壓氧治療糖尿病鼠之研究
論文名稱(英文) The merit of hyperbaic oxygen therapy in diabetic rats
校院名稱 成功大學
系所名稱(中) 藥理學研究所
系所名稱(英) Department of Pharmacology
學年度 97
學期 2
出版年 98
研究生(中文) 洪堯軒
研究生(英文) Yao-hsuan Hung
電子信箱 snapcool@yahoo.com.tw
學號 S2696402
學位類別 碩士
語文別 中文
論文頁數 68頁
口試委員 指導教授-鄭瑞棠
指導教授-洪正路
口試委員-牛柯琪
中文關鍵字 糖尿病  高壓氧治療 
英文關鍵字 diabetes  hyperbaric oxygen therapy 
學科別分類
中文摘要 所謂高壓氧治療 (hyperbaric oxygen therapy, HBOT),即藉由提高氧分壓,促使更多的氧氣溶入血液循環中。並且,在臨床上常用於解決傷口創傷等問題,其中包括糖尿病人易發生的糖尿病足。先前文獻指出,人體暴露在高壓氧環境下,體內β-腦內啡 (β-endorphin)的量會有明顯增加的情況。此外,β-腦內啡具有調節體內醣類恆定的作用。然而,高壓氧治療是否會藉由促進β-腦內啡釋放增加進而調節醣類恆定目前仍不清楚。本實驗結果發現,STZ (streptozocin)誘導之第一型糖尿病鼠在高壓氧治療之下,其體內β-腦內啡是增加的,且其原本在高壓氧治療之下所導致的降血糖作用,可以藉由前處理嗎啡受體拮抗劑naloxone或嗎啡μ型受體拮抗劑naloxonazine達到抑制的作用。這些結果指出高壓氧治療可以藉由提高體內β-腦內啡的表現,進而活化嗎啡μ型受體而達到降低血糖的作用。接著,結果發現,在前處理NMDA接受體拮抗劑MK801或菸鹼受體拮抗劑hexmethonium後,可以抑制高壓氧治療所產生的降血糖作用及β-腦內啡增加的現象,且去除腎上腺第一型糖尿病鼠或糖尿病鼠經脊髓截斷手術後,在高壓氧治療後,也看到同樣的抑制效果。此結果可以得知,高壓氧治療可以藉由中樞NMDA接受體活化所產生的神經傳遞作用,促進腎上腺髓質菸鹼受體活化,進而促使β-腦內啡分泌,達到降血糖的作用。另一方面,已知β-腦內啡可以改變骨骼肌葡萄醣轉運蛋白 (glucose transport type 4, GLUT4)的表現促使葡萄糖的攝入增加,其也可以促進肝臟肝醣的合成並抑制肝臟中的磷酸烯醇式丙酮酸羧激 (phosphoenolpyruvatecarboxykinase, PEPCK),降低醣質新生作用,故有調節醣類恆定與降低血糖的作用。肝臟中蛋白質激C ζ (protein kinase C ζ, PKCζ)的活化可以抑制肝醣合成激-3β(glycogen synthase kinase 3β, GSK3β),故有促進肝醣合成的作用。從實驗結果發現,糖尿病鼠在經三天的高壓氧治療後,其骨骼肌膜上蛋白GLUT4表現有增加的情形,肝臟中PEPCK的表現是降低的,且肝臟中的PKCζ及GSK3β磷酸化有增加的現象,以及肝醣的堆積有增加的情況。這些結果皆可以藉由前處理嗎啡μ型受體拮抗劑naloxonazine而受到抑制。綜合以上結果,本研究發現,高壓氧治療藉由β-腦內啡的釋放有助於第一型糖尿病鼠改善醣類恆定。
英文摘要 Abstract
Hyperbaric oxygen therapy (HBOT) was defined as a treatment that made more oxygen dissolved in blood circulation by raising the partial pressure of oxygen, and was usually used to deal with wound problems including diabetic foot ulcer. Previous study indicates that plasma β-endorphin was increased in human after acute hyperbaric oxygen exposure. β-Endorphin is known to regulate glucose homeostasis. Howerver, whether HBOT regulates glucose homeostasis through β-endorphin release is still obscure. In the present study, we found that HBOT increased plasma β-endorphin release in streptozocin (STZ) diabetic rats. Moreover, HBOT exerted a blood glucose-lowering action, which was recovered by naloxone or naloxonazine pretreatment. These results indicated that decreased blood glucose induced by HBOT was through β-endorphin release to activate opioid μ-receptor. The decrease of blood glucose and β-endorphin increment in HBOT-treated STZ diabetic rats were also suppressed by pretreatment with MK801 (NMDA receptor antagonist) and hexamethonium (nicotinic receptor antagonist), as well as adrenalectomy and spinal cord truncation. Thus, the obtained data suggest that HBOT might activate NMDA neurotransmission in brain to increase β-endorphin release from adrenal gland through an activation of nicotinic neurotransmission. On the other hand, β-endorphin is known to not only raise glucose transport type 4 (GLUT4) expression to increase glucose uptake in skeletal muscle, but also decrease phosphoenolpyruvatecarboxykinase (PEPCK) expression to reduce gluconeogenesis in liver. β-Endorphin also promotes hepatic glycogen synthesis. Activation of protein kinase C ζ (PKCζ) inhibits glycogen synthase kinase 3β (GSK3β) activity to increase hepatic glycogen synthesis. In our study, STZ diabetic rats after received HBOT for three days had elevated membrane Glut4 and lowered PEPCK expression, as well as increased phosorylation of PKC ζ and GSK3β and glycogen content, which were all reversed by naloxonazine. Taken together, we found, at least in part, HBOT had benefits for diabetic care in STZ diabetic rats through β-endorphin release to improve glucose homeostasis.
論文目次 中文摘要............................................................................................I
英文摘要...........................................................................................IV
縮寫表...............................................................................................VIII
第一章 緒論.....................................................................................1
第二章 實驗方法與材料.................................................................9
第三章 實驗結果.............................................................................25
第四章 討論.....................................................................................33
第五章 結論.....................................................................................38
參考文獻...........................................................................................40
附圖...................................................................................................53
參考文獻 Reference

[1] S. Wild, G. Roglic, A. Green, R. Sicree, and H. King, Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27 (2004) 1047-53.

[2] A.H. Mokdad, E.S. Ford, B.A. Bowman, W.H. Dietz, F. Vinicor, V.S. Bales, and J.S. Marks, Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. J Am Med Assoc 289 (2003) 76-9.

[3] B. Mlinar, J. Marc, A. Janez, and M. Pfeifer, Molecular mechanisms of insulin resistance and associated diseases. Clin Chim Acta 375 (2007) 20-35.

[4] D.P. Brazil, and B.A. Hemmings, Ten years of protein kinase B signalling: a hard Akt to follow. Trends Biochem Sci 26 (2001) 657-64.

[5] L. Pirola, A.M. Johnston, and E. Van Obberghen, Modulation of insulin action. Diabetologia 47 (2004) 170-84.

[6] A.R. Saltiel, and C.R. Kahn, Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414 (2001) 799-806.

[7] J.G. Neels, and J.M. Olefsky, Inflamed fat: what starts the fire? J Clin Invest 116 (2006) 33-5.

[8] M.W. Rajala, and P.E. Scherer, Minireview: The adipocyte--at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 144 (2003) 3765-73.

[9] H. Xu, G.T. Barnes, Q. Yang, G. Tan, D. Yang, C.J. Chou, J. Sole, A. Nichols, J.S. Ross, L.A. Tartaglia, and H. Chen, Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112 (2003) 1821-30.


[10] A.R. Saltiel, New perspectives into the molecular pathogenesis and treatment of type 2 diabetes. Cell 104 (2001) 517-29.

[11] D. Devendra, E. Liu, and G.S. Eisenbarth, Type 1 diabetes: recent developments. Br Med J 328 (2004) 750-4.

[12] A.P. Lambert, K.M. Gillespie, G. Thomson, H.J. Cordell, J.A. Todd, E.A. Gale, and P.J. Bingley, Absolute risk of childhood-onset type 1 diabetes defined by human leukocyte antigen class II genotype: a population-based study in the United Kingdom. J Clin Endocrinol Metab 89 (2004) 4037-43.

[13] M.J. Redondo, P.R. Fain, and G.S. Eisenbarth, Genetics of type 1A diabetes. Recent Prog Horm Res 56 (2001) 69-89.

[14] M.A. Atkinson, and G.S. Eisenbarth, Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 358 (2001) 221-9.

[15] K.M. Gillespie, Type 1 diabetes: pathogenesis and prevention. Can
Med Assoc J 175 (2006) 165-70.

[16] The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 329 (1993) 977-86.

[17] Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 352 (1998) 837-53.

[18] M. Brownlee, A radical explanation for glucose-induced beta cell dysfunction. J Clin Invest 112 (2003) 1788-90.




[19] T. Nishikawa, D. Edelstein, X.L. Du, S. Yamagishi, T. Matsumura, Y. Kaneda, M.A. Yorek, D. Beebe, P.J. Oates, H.P. Hammes, I. Giardino, and M. Brownlee, Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404 (2000) 787-90.

[20] R. Pop-Busui, A. Sima, and M. Stevens, Diabetic neuropathy and oxidative stress. Diabetes Metab Res Rev 22 (2006) 257-73.

[21] P. Rosen, P.P. Nawroth, G. King, W. Moller, H.J. Tritschler, and L. Packer, The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCO-MCBN, the American Diabetes Association and the German Diabetes Society. Diabetes Metab Res Rev 17 (2001) 189-212.

[22] H. Ha, and H.B. Lee, Reactive oxygen species as glucose signaling molecules in mesangial cells cultured under high glucose. Kidney Int Suppl 77 (2000) 19-25.

[23] H.B. Lee, M.R. Yu, Y. Yang, Z. Jiang, and H. Ha, Reactive oxygen species-regulated signaling pathways in diabetic nephropathy. J Am Soc Nephrol 14 (2003) 241-5.

[24] N.A. Calcutt, M.E. Cooper, T.S. Kern, and A.M. Schmidt, Therapies for hyperglycaemia-induced diabetic complications: from animal models to clinical trials. Nat Rev Drug Discov 8 (2009) 417-29.

[25] P.M. Tibbles and J.S, Hyperbaric-oxygen therapy. N Engl J Med 334(1996) 1642-1648

[26] A.L. Gill, and C.N. Bell, Hyperbaric oxygen: its uses, mechanisms of action and outcomes. An Int J Med 97 (2004) 385-95.

[27] B.M. Palmquist, B. Philipson, and P.O. Barr, Nuclear cataract and myopia during hyperbaric oxygen therapy. Br J Ophthalmol 68 (1984) 113-7.

[28] N. Hampson, and D. Atik, Central nervous system oxygen toxicity during routine hyperbaric oxygen therapy. Undersea Hyperb Med 30 (2003) 147-53.

[29] K.L. Huang, J.N. Wu, H.C. Lin, S.P. Mao, B. Kang, and F.J. Wan, Prolonged exposure to hyperbaric oxygen induces neuronal damage in primary rat cortical cultures. Neurosci Lett 293 (2000) 159-62.

[30] C.A. Colton, and J.S. Colton, Blockade of hyperbaric oxygen induced seizures by excitatory amino acid antagonists. Can J Physiol Pharmacol 63 (1985) 519-21.

[31] F. Dexter, and B.J. Hindman, Recommendations for hyperbaric oxygen therapy of cerebral air embolism based on a mathematical model of bubble absorption. Anesth Analg 84 (1997) 1203-7.

[32] A.B. Branger, C.J. Lambertsen, and D.M. Eckmann, Cerebral gas embolism absorption during hyperbaric therapy: theory. J Appl Physiol 90 (2001) 593-600.

[33] R.E. Moon, and P.J. Sheffield, Guidelines for treatment of decompression illness. Aviat Space Environ Med 68 (1997) 234-43.

[34] T.K. Hunt, The physiology of wound healing. Ann Emerg Med 17 (1988) 1265-73.

[35] D.R. Knighton, I.A. Silver, and T.K. Hunt, Regulation of wound-healing angiogenesis-effect of oxygen gradients and inspired oxygen concentration. Surgery 90 (1981) 262-70.

[36] P. Gregorevic, G.S. Lynch, and D.A. Williams, Hyperbaric oxygen modulates antioxidant enzyme activity in rat skeletal muscles. Eur J Appl Physiol 86 (2001) 24-7.




[37] M.T. Conconi, S. Baiguera, D. Guidolin, C. Furlan, A.M. Menti, S. Vigolo, A.S. Belloni, P.P. Parnigotto, and G.G. Nussdorfer, Effects of hyperbaric oxygen on proliferative and apoptotic activities and reactive oxygen species generation in mouse fibroblast 3T3/J2 cell line. J Investig Med 51 (2003) 227-32.

[38] S. Benedetti, A. Lamorgese, M. Piersantelli, S. Pagliarani, F. Benvenuti, and F. Canestrari, Oxidative stress and antioxidant status in patients undergoing prolonged exposure to hyperbaric oxygen. Clin Biochem 37 (2004) 312-7.

[39] C.K. Narkowicz, J.H. Vial, and P.W. McCartney, Hyperbaric oxygen therapy increases free radical levels in the blood of humans. Free Radic Res Commun 19 (1993) 71-80.

[40] C. Dennog, C. Gedik, S. Wood, and G. Speit, Analysis of oxidative DNA damage and HPRT mutations in humans after hyperbaric oxygen treatment. Mutat Res 431 (1999) 351-9.

[41] A. Rothfuss, P. Radermacher, and G. Speit, Involvement of heme oxygenase-1 (HO-1) in the adaptive protection of human lymphocytes after hyperbaric oxygen (HBO) treatment. Carcinogenesis 22 (2001) 1979-85.

[42] V. Calabrese, C. Mancuso, M. Calvani, E. Rizzarelli, D.A. Butterfield, and A.M. Stella, Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity. Nat Rev Neurosci 8 (2007) 766-75.

[43] M. Ushio-Fukai, and R.W. Alexander, Reactive oxygen species as mediators of angiogenesis signaling: role of NAD(P)H oxidase. Mol Cell Biochem 264 (2004) 85-97.

[44] N. Maulik, Redox signaling of angiogenesis. Antioxid Redox Signal 4 (2002) 805-15.


[45] K.A. Gallagher, Z.J. Liu, M. Xiao, H. Chen, L.J. Goldstein, D.G. Buerk, A. Nedeau, S.R. Thom, and O.C. Velazquez, Diabetic impairments in NO-mediated endothelial progenitor cell mobilization and homing are reversed by hyperoxia and SDF-1 alpha. J Clin Invest 117 (2007) 1249-59.

[46] L.J. Goldstein, K.A. Gallagher, S.M. Bauer, R.J. Bauer, V. Baireddy, Z.J. Liu, D.G. Buerk, S.R. Thom, and O.C. Velazquez, Endothelial progenitor cell release into circulation is triggered by hyperoxia-induced increases in bone marrow nitric oxide. Stem Cells 24 (2006) 2309-18.

[47] A.Y. Sheikh, J.J. Gibson, M.D. Rollins, H.W. Hopf, Z. Hussain, and T.K. Hunt, Effect of hyperoxia on vascular endothelial growth factor levels in a wound model. Arch Surg 135 (2000) 1293-7.

[48] P. Kranke, M. Bennett, I. Roeckl-Wiedmann, and S. Debus, Hyperbaric oxygen therapy for chronic wounds. Cochrane Database Syst Rev (2004) CD004123.

[49] C.L. Hess, M.A. Howard, and C.E. Attinger, A review of mechanical adjuncts in wound healing: hydrotherapy, ultrasound, negative pressure therapy, hyperbaric oxygen, and electrostimulation. Ann Plast Surg 51 (2003) 210-8.

[50] S.R. Thom, V.M. Bhopale, D.J. Mancini, and T.N. Milovanova, Actin S-nitrosylation inhibits neutrophil beta2 integrin function. J Biol Chem 283 (2008) 10822-34.

[51] J.A. Buras, G.L. Stahl, K.K. Svoboda, and W.R. Reenstra, Hyperbaric oxygen downregulates ICAM-1 expression induced by hypoxia and hypoglycemia: the role of NOS. Am J Physiol Cell Physiol 278 (2000) 292-302.




[52] K. Kihara, S. Ueno, M. Sakoda, and T. Aikou, Effects of hyperbaric oxygen exposure on experimental hepatic ischemia reperfusion injury: relationship between its timing and neutrophil sequestration. Liver Transpl 11 (2005) 1574-80.

[53] S.R. Thom, I. Mendiguren, and D. Fisher, Smoke inhalation-induced alveolar lung injury is inhibited by hyperbaric oxygen. Undersea Hyperb Med 28 (2001) 175-9.

[54] D.N. Atochin, D. Fisher, I.T. Demchenko, and S.R. Thom, Neutrophil sequestration and the effect of hyperbaric oxygen in a rat model of temporary middle cerebral artery occlusion. Undersea Hyperb Med 27 (2000) 185-90.

[55] G.E. Reiber, L. Vileikyte, E.J. Boyko, M. del Aguila, D.G. Smith, L.A. Lavery, and A.J. Boulton, Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings. Diabetes Care 22 (1999) 157-62.

[56] H. Brem, and M. Tomic-Canic, Cellular and molecular basis of wound healing in diabetes. J Clin Invest 117 (2007) 1219-22.

[57] H. Galkowska, U. Wojewodzka, and W.L. Olszewski, Chemokines, cytokines, and growth factors in keratinocytes and dermal endothelial cells in the margin of chronic diabetic foot ulcers. Wound Repair Regen 14 (2006) 558-65.

[58] V. Falanga, Wound healing and its impairment in the diabetic foot. Lancet 366 (2005) 1736-43.

[59] R.D. Galiano, O.M. Tepper, C.R. Pelo, K.A. Bhatt, M. Callaghan, N. Bastidas, S. Bunting, H.G. Steinmetz, and G.C. Gurtner, Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells. Am J Pathol 164 (2004) 1935-47.


[60] K. Maruyama, J. Asai, M. Ii, T. Thorne, D.W. Losordo, and P.A. D'Amore, Decreased macrophage number and activation lead to reduced lymphatic vessel formation and contribute to impaired diabetic wound healing. Am J Pathol 170 (2007) 1178-91.


[61] N.S. Gibran, Y.C. Jang, F.F. Isik, D.G. Greenhalgh, L.A. Muffley, R.A. Underwood, M.L. Usui, J. Larsen, D.G. Smith, N. Bunnett, J.C. Ansel, and J.E. Olerud, Diminished neuropeptide levels contribute to the impaired cutaneous healing response associated with diabetes mellitus. J Surg Res 108 (2002) 122-8.

[62] J.P. Hailey D, Perry D, Chuck A, Morrison A, Bondreau R. , Technology Report: adjunctive hyperbaric oxygen therapy for diabetic foot ulcer: an economic analysis. Canadian Agency for Drugs and Technologies in Health, 2007.

[63] C.F. Potter, N.T. Kuo, C.F. Farver, J.T. McMahon, C.H. Chang, F.H. Agani, M.A. Haxhiu, and R.J. Martin, Effects of hyperoxia on nitric oxide synthase expression, nitric oxide activity, and lung injury in rat pups. Pediatr Res 45 (1999) 8-13.

[64] Dedov, II, V.L. Lukich, T.D. Bol'shakova, E.P. Gitel, and A.V. Dreval, [Effect of hyperbaric oxygenation on residual insulin secretion in patients with diabetes mellitus type 1]. Probl Endokrinol (Mosk) 33 (1987) 10-5.

[65] K. Yasuda, T. Adachi, N. Gu, A. Matsumoto, T. Matsunaga, G. Tsujimoto, K. Tsuda, and A. Ishihara, Effects of hyperbaric exposure with high oxygen concentration on glucose and insulin levels and skeletal muscle-fiber properties in diabetic rats. Muscle Nerve 35 (2007) 337-43.





[66] N.S. Al-Waili, G.J. Butler, J. Beale, M.S. Abdullah, M. Finkelstein, M. Merrow, R. Rivera, R. Petrillo, Z. Carrey, B. Lee, and M. Allen, Influences of hyperbaric oxygen on blood pressure, heart rate and blood glucose levels in patients with diabetes mellitus and hypertension. Arch Med Res 37 (2006) 991-7.

[67] S. Solomon, POMC-derived peptides and their biological action. Ann N Y Acad Sci 885 (1999) 22-40.

[68] E. Charmandari, C. Tsigos, and G. Chrousos, Endocrinology of the stress response. Annu Rev Physiol 67 (2005) 259-84.
[69] I. Berczi, I.M. Chalmers, E. Nagy, and R.J. Warrington, The immune effects of neuropeptides. Baillieres Clin Rheumatol 10 (1996) 227-57.

[70] J.E. Holden, Y. Jeong, and J.M. Forrest, The endogenous opioid system and clinical pain management. American Association of Critical-Care Nurses Clin Issues 16 (2005) 291-301.

[71] J.M. Farah, Jr., T.S. Rao, S.J. Mick, K.E. Coyne, and S. Iyengar, N-methyl-D-aspartate treatment increases circulating adrenocorticotropin and luteinizing hormone in the rat. Endocrinology 128 (1991) 1875-80.

[72] D. Giugliano, and P.J. Lefebvre, A role for beta-endorphin in the pathogenesis of human obesity? Horm Metab Res 23 (1991) 251-6.

[73] J.F. Dalayeun, J.M. Nores, and S. Bergal, Physiology of beta-endorphins. A close-up view and a review of the literature. Biomed Pharmacother 47 (1993) 311-20.

[74] A. Casti, G. Orlandini, M.G. Troglio, F. Bacciottini, M. Michelini, L. Maninetti, G. Vezzani, G. Rastelli, and P. Vescovi, Acute and chronic hyperbaric oxygen exposure in humans: effects on blood polyamines, adrenocorticotropin and beta-endorphin. Acta Endocrinol (Copenh) 129 (1993) 436-41.


[75] J.T. Cheng, I.M. Liu, T.F. Tzeng, C.C. Tsai, and T.Y. Lai, Plasma glucose-lowering effect of beta-endorphin in streptozotocin-induced diabetic rats. Horm Metab Res 34 (2002) 570-6.

[76] C.F. Su, Y.Y. Chang, H.H. Pai, I.M. Liu, C.Y. Lo, and J.T. Cheng, Infusion of beta-endorphin improves insulin resistance in fructose-fed rats. Horm Metab Res 36 (2004) 571-7.

[77] J.T. Cheng, C.C. Huang, I.M. Liu, T.F. Tzeng, and C.J. Chang, Novel mechanism for plasma glucose-lowering action of metformin in streptozotocin-induced diabetic rats. Diabetes 55 (2006) 819-25.
[78] S.L. Hwang, I.M. Liu, T.F. Tzeng, and J.T. Cheng, Activation of imidazoline receptors in adrenal gland to lower plasma glucose in streptozotocin-induced diabetic rats. Diabetologia 48 (2005) 767-75.

[79] J.H. Hsu, Y.C. Wu, S.S. Liou, I.M. Liu, L.W. Huang, and J.T. Cheng, Mediation of Endogenous beta-endorphin by Tetrandrine to Lower Plasma Glucose in Streptozotocin-induced Diabetic Rats. Evid Based Complement Alternat Med 1 (2004) 193-201.

[80] M.G. Kolta, L.J. Wallace, and M.C. Gerald, Streptozocin-induced diabetes affects rat urinary bladder response to autonomic agents. Diabetes 34 (1985) 917-21.

[81] S.L. Chang, J.G. Lin, T.C. Chi, I.M. Liu, and J.T. Cheng, An insulin-dependent hypoglycaemia induced by electroacupuncture at the Zhongwan (CV12) acupoint in diabetic rats. Diabetologia 42 (1999) 250-5.

[82] S. Okada, N. Yamaguchi-Shima, T. Shimizu, J. Arai, M. Yorimitsu, and K. Yokotani, Centrally administered N-methyl-d-aspartate evokes the adrenal secretion of noradrenaline and adrenaline by brain thromboxane A2-mediated mechanisms in rats. Eur J Pharmacol 586 (2008) 145-50.



[83] P. Dinh, N. Bhatia, A. Rasouli, S. Suryadevara, K. Cahill, and R. Gupta, Transplantation of preconditioned Schwann cells following hemisection spinal cord injury. Spine 32 (2007) 943-9.

[84] A. Rasouli, N. Bhatia, S. Suryadevara, K. Cahill, and R. Gupta, Transplantation of preconditioned schwann cells in peripheral nerve grafts after contusion in the adult spinal cord. Improvement of recovery in a rat model. J Bone Joint Surg Am 88 (2006) 2400-10.

[85] J.T. Cheng, I.M. Liu, T.C. Chi, and T.F. Tzeng, Increase of opioid mu-receptor gene expression in streptozotocin-induced diabetic rats. Horm Metab Res 33 (2001) 467-71.
[86] J.D. Wood, W.J. Watson, and G.W. Murray, Correlation between decreases in brain gamma-aminobutyric acid levels and susceptibility to convulsions induced by hyperbaric oxygen. J Neurochem 16 (1969) 281-7.

[87] S. Zhang, Y. Takeda, S. Hagioka, K. Goto, and K. Morita, The close relationship between decreases in extracellular GABA concentrations and increases in the incidence of hyperbaric oxygen-induced electrical discharge. Acta Med Okayama 58 (2004) 91-5.

[88] S. Zhang, Y. Takeda, S. Hagioka, K. Takata, H. Aoe, H. Nakatsuka, M. Yokoyama, and K. Morita, Measurement of GABA and glutamate in vivo levels with high sensitivity and frequency. Brain Res Protoc 14 (2005) 61-6.

[89] S. Okada, Y. Murakami, M. Nishihara, K. Yokotani, and Y. Osumi, Perfusion of the hypothalamic paraventricular nucleus with N-methyl-D-aspartate produces thromboxane A2 and centrally activates adrenomedullary outflow in rats. Neuroscience 96 (2000) 585-90.

[90] A.S. Jansen, X.V. Nguyen, V. Karpitskiy, T.C. Mettenleiter, and A.D. Loewy, Central command neurons of the sympathetic nervous system: basis of the fight-or-flight response. Science 270 (1995) 644-6.


[91] Y.H. Zhang, J. Lu, J.K. Elmquist, and C.B. Saper, Lipopolysaccharide activates specific populations of hypothalamic and brainstem neurons that project to the spinal cord. J Neurosci 20 (2000) 6578-86.

[92] M. Gaster, P. Staehr, H. Beck-Nielsen, H.D. Schroder, and A. Handberg, GLUT4 is reduced in slow muscle fibers of type 2 diabetic patients: is insulin resistance in type 2 diabetes a slow, type 1 fiber disease? Diabetes 50 (2001) 1324-9.

[93] M. Gaster, P. Poulsen, A. Handberg, H.D. Schroder, and H. Beck-Nielsen, Direct evidence of fiber type-dependent GLUT-4 expression in human skeletal muscle. Am J Physiol Endocrinol Metab 278 (2000) 910-6.

[94] H.K. Kramer, and E.J. Simon, Role of protein kinase C (PKC) in agonist-induced mu-opioid receptor down-regulation: II. Activation and involvement of the alpha, epsilon, and zeta isoforms of PKC. J Neurochem 72 (1999) 594-604.

[95] X.J. Liu, A.B. He, Y.S. Chang, and F.D. Fang, Atypical protein kinase C in glucose metabolism. Cell Signal 18 (2006) 2071-6.
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