現今全球罹患糖尿病之人口高達三億多人，其中90~95%屬於第2型糖尿病，在我國糖尿病也已成為國人主要之慢性病之一，而高血糖所誘發之氧化壓力增加，會造成粒線體功能缺失。文獻指出，山竹果皮萃取物具有抗氧化、抗發炎之功效，但能否改善糖尿病粒線體功能缺失的情形仍然未知。本研究是以注射streptozotocin合併nicotinamide 誘發之第2型糖尿病大鼠模式，探討給予山竹濃縮果汁對於血糖及肝臟粒線體之影響。實驗大鼠分為對照組 (N) 與實驗組，實驗組又分為糖尿病 (C) 組及飼料添加山竹濃縮果汁低 (L: 0.5 mL/day) 、中 (M: 1.0 mL/day) 、高 (H: 2.0 mL/day) 劑量組，實驗為期八週後進行犧牲，取其血液及肝臟進行分析。研究結果發現，以山竹濃縮果汁飼養八週後可顯著降低第2型糖尿病大鼠禁食血糖，且可抑制葡萄糖耐受試驗180分鐘血糖曲線下面積之增加；增加catalase、glutathione reductase、glutathione peroxidase及SOD等抗氧化酵素活性，降低TBARS (Thiobarbituric acid reactive substances)濃度，並增加粒線體NCCR (nicotinamide adenine dinucleotide (NADH)-cytochrome c reductase)及SCCR (succinate-cytochrome c reductase)之酵素活性；總合以上結論，山竹濃縮果汁的補充對於第2型糖尿病大鼠可增加其體內之抗氧化能力，並改善粒線體功能缺失之情形，有助於糖尿病之血糖調控。

There are 347 million people with diabetes worldwide, whereas 90% comprises of Type 2 diabetes. Diabetes mellitus (DM) is one of the major chronic disease in Taiwan. Hyperglycemia induced oxidative stress causes mitochondrial dysfunction. Mangosteen (Garcinia mangostana) pericarp extract is rich in xanthone, and exhibits strong antioxidant, anti-inflammatory, and antitumor activities. However, its potential to ameliorate mitochondrial dysfunction in diabetes is unknown. Therefore, the purpose of this study was to investigate the effects of mangosteen mix juice on liver mitochondrial functions in type 2 diabetic rats. DM was induced in male Wistar rats by intraperitoneal injection of streptozotocin/nicotinamide. The experiment was divided in to five groups: (N) normal group (C) DM group (L) DM group + low dose mangosteen mix juice (0.5ml/day), (M) DM group + medium dose mangosteen mix juice (1ml/day) , (H) DM group + high dose mangosteen mix juice (2ml/day). After 8 weeks, rats were sacrificed and examined liver tissues for activity of superoxidase dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and thiobiobarbitric acid reactive substances (TBARS). Liver mitochondria were analysed for nicotinamide adenine dinucleotide cytochrome c reductase (NCCR), succinate cytochrome c reductase (SCCR), respiratory control ratio (RCR), and mtDNA copy number. The results showed significantly lower plasma glucose in the M and H groups than in the group C. Mangosteen mix juice consumption prevented increased glucose (AUC 0-180 min) after intraperitoneal injection of in rats. The M, and H group had significantly increased CAT and SOD activities compared with respective activities in group C. The GR and GPx activity was significantly higher in L, M, and H groups showed than in group C. L, M, and H group had significantly lower hepatic TBARS than group C. NCCR and SCCR activities in L, M, and H groups were significantly higher than activity in group C. RCR and mtDNA copy number in L, M, and H groups were significantly higher than group C. In conclusion, mangosteen mix juice consumption increased hepatic antioxidant capacity, improved mitochondrial function, and controlled type 2 diabetes blood sugar homeostasis.

目錄
目錄................................................... i
表目錄................................................. iv
圖目錄................................................. vi
摘要................................................... vii
Abstract............................................... 8
第一章 前言............................................ 9
第二章 文獻回顧........................................ 11
第一節 糖尿病......................................... 11
一、流行病學......................................... 11
二、簡介............................................. 11
三、糖尿病分類....................................... 13
(一)第1型糖尿病 (type 1 diabetes)................... 13
(二)第2型糖尿病 (Type 2 diabetes)................... 13
(三)妊娠型糖尿病 (gestational diabetes, GDM)........ 14
四、Streptozotocin (STZ)............................. 14
(一)致病機轉........................................ 15
(二)以nicotinamide (NA)合併STZ誘發動物高血糖之機制與原
理.............................................. 16
第二節 粒線體......................................... 18
一、粒線體概述與功能................................. 18
二、粒線體之電子傳遞鏈與氧化磷酸化功能............... 19
三、粒線體功能評估................................... 20
四、粒線體與氧化壓力................................. 21
五、氧化壓力、糖尿病與粒線體之關聯性................. 22
六、粒線體與STZ...................................... 23
第三節 山竹........................................... 25
一、山竹簡介：....................................... 25
二、傳統醫療功效..................................... 26
三、活性成分......................................... 27
四、生理活性......................................... 28
(一)抗氧化功能...................................... 28
(二)抗腫瘤.......................................... 29
(三)抗發炎與抗過敏作用.............................. 30
五、安全性評估....................................... 31
第三章 研究目的........................................ 33
第四章 材料與方法...................................... 34
一、實驗設計......................................... 34
二、第2型糖尿病誘發.................................. 37
三、樣品採集及處理................................... 38
四、分析項目......................................... 38
(一)血液樣品分析.................................... 38
(二)肝臟樣品分析.................................... 42
(三)粒線體功能分析.................................. 46
(四)肝臟粒線體DNA................................... 48
第五章 統計分析........................................ 50
第六章 結果............................................ 51
一、體重及攝食量變化................................. 51
二、禁食血漿葡萄糖及脂質濃度變化..................... 51
三、腹腔注射葡萄糖耐受試驗180分鐘血糖曲線下面積...... 52
四、肝臟抗氧化酵素活性及脂質過氧化終產物濃度......... 52
五、肝臟粒線體呼吸傳遞鏈複合體酵素活性............... 53
六、肝臟粒線體呼吸控制率............................. 54
七、肝臟粒線體DNA套數................................ 54
第七章 討論............................................ 55
一、山竹濃縮果汁對攝食量及體重之影響................. 55
二、山竹濃縮果汁對血糖恆定之影響..................... 55
三、山竹濃縮果汁對肝臟抗氧化酵素活性之影響........... 57
四、山竹濃縮果汁對肝臟粒線體功能之影響............... 59
五、山竹濃縮果汁對糖尿病之影響....................... 60
第八章 結論............................................ 61
第九章 參考文獻........................................ 62
附錄................................................... 91

Akao Y, Nakagawa Y, Iinuma M, Nozawa Y: Anti-cancer effects ofxanthones from pericarps of mangosteen. Int J Mol Sci 2008,9:355-370.

Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR,Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, et al:Sequence and organization of the human mitochondrial genome.Nature 1981, 290:457-465.

Antuna-Puente B, Disse E, Rabasa-Lhoret R, Laville M, Capeau J,Bastard J-P: How can we measure insulin sensitivity/resistance? Diabetes Metab 2011, 37:179-188.

Balunas MJ, Su B, Brueggemeier RW, Kinghorn AD: Xanthones from the botanical dietary supplement mangosteen (Garcinia
mangostana) with aromatase inhibitory activity. J Nat Prod 2008,71:1161-1166.

Bhuyan BK, Kuentzel SL, Gray LG, Fraser TJ, Wallach D, Neil GL:Tissue distribution of streptozotocin (NSC-85998). Cancer
Chemother Rep 1974, 58:157-165.

Boden G: Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes 1997, 46:3-10.

Boveris A, Cadenas E, Stoppani AO: Role of ubiquinone in the
mitochondrial generation of hydrogen peroxide. Biochem J 1976,156:435-444.

Chairungsrilerd N, Furukawa K, Ohta T, Nozoe S, Ohizumi Y:
Pharmacological properties of alpha-mangostin, a novel
histamine H1 receptor antagonist. Eur J Pharmacol 1996,
314:351-356.


CHAIRUNGSRILERD N, TAKEUCHI K, OH1ZUMI Y, NOZOE S,
OHTA T: Mangostanol, a prenyl xanthone from Garcinia
mangostana. Phvtochemistry 1996, 43:1099-1102.

Chen LG, Yang LL, Wang CC: Anti-inflammatory activity of
mangostins from Garcinia mangostana. Food Chem Toxicol 2008,
46:688-693.

Chen Q, Vazquez EJ, Moghaddas S, Hoppel CL, Lesnefsky EJ:
Production of reactive oxygen species by mitochondria: central role of complex III. J Biol Chem 2003, 278:36027-36031.

Chen SX, Wan M, Loh BN: Active constituents against HIV-1 protease from Garcinia mangostana. Planta Med 1996, 62:381-382.

Chinopoulos C, Adam-Vizi V: Mitochondria deficient in complex I activity are depolarized by hydrogen peroxide in nerve terminals:relevance to Parkinson''s disease. J Neurochem 2001, 76:302-306.

Chivapat S, Wongsinkongman PCP, Rungsipipat CPA: Chronic Toxicity Study of Garcinia mangostana Linn. pericarp Extract. Thai Journal of Veterinary Medicine 2011, 41:45-53.

Chomnawang MT, Surassmo S, Nukoolkarn VS, Gritsanapan W:
Antimicrobial effects of Thai medicinal plants against
acne-inducing bacteria. J Ethnopharmacol 2005, 101:330-333.

Chomnawang MT, Surassmo S, Wongsariya K, Bunyapraphatsara N:
Antibacterial activity of Thai medicinal plants against
methicillin-resistant Staphylococcus aureus. Fitoterapia 2009,80:102-104.

Devi Sampath P, Vijayaraghavan K: Cardioprotective effect of
alpha-mangostin, a xanthone derivative from mangosteen on
tissue defense system against isoproterenol-induced myocardial infarction in rats. J Biochem Mol Toxicol 2007, 21:336-339.

Doi H, Shibata MA, Shibata E, Morimoto J, Akao Y, Iinuma M,
Tanigawa N, Otsuki Y: Panaxanthone isolated from pericarp of
Garcinia mangostana L. suppresses tumor growth and
metastasis of a mouse model of mammary cancer. Anticancer Res 2009, 29:2485-2495.

Einhorn D, Reaven GM, Cobin RH, Ford E, Ganda OP, Handelsman Y, Hellman R, Jellinger PS, Kendall D, Krauss RM, et al: American College of Endocrinology position statement on the insulin resistance syndrome. Endocr Pract 2003, 9:237-252.

Elsner M, Guldbakke B, Tiedge M, Munday R, Lenzen S: Relative importance of transport and alkylation for pancreatic beta-cell toxicity of streptozotocin. Diabetologia 2000, 43:1528-1533.

Evans JL, Goldfine ID, Maddux BA, Grodsky GM: Are oxidative
stress-activated signaling pathways mediators of insulin
resistance and beta-cell dysfunction? Diabetes 2003, 52:1-8.

Fariss MW, Chan CB, Patel M, Van Houten B, Orrenius S: Role of mitochondria in toxic oxidative stress. Mol Interv 2005, 5:94-111.

Farnsworth NR, Bunyapraphatsara N: Thai Medicinal
Plant:Recommended for Primary Health Care System. Agbe
Publishing; 1992.

Fernie AR, Carrari F, Sweetlove LJ: Respiratory metabolism:
glycolysis, the TCA cycle and mitochondrial electron transport. Curr Opin Plant Biol 2004, 7:254-261.

Ferreira FM, Palmeira CM, Seica R, Moreno AJ, Santos MS: Diabetes and mitochondrial bioenergetics: alterations with age. J Biochem Mol Toxicol 2003, 17:214-222.

Gao Z, Hwang D, Bataille F, Lefevre M, York D, Quon MJ, Ye J: Serine phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex. J Biol Chem 2002, 277:48115-48121.

Gershon D: The mitochondrial theory of aging: is the culprit a faulty disposal system rather than indigenous mitochondrial alterations?Exp Gerontol 1999, 34:613-619.

Goldmacher VS, Cuzick RA, Jr., Thilly WG: Isolation and partial characterization of human cell mutants differing in sensitivity to killing and mutation by methylnitrosourea and
N-methyl-N''-nitro-N-nitrosoguanidine. J Biol Chem 1986,
261:12462-12471.

Halliwell B, Gutteridge JM: Lipid peroxidation, oxygen radicals, cell damage, and antioxidant therapy. Lancet 1984, 1:1396-1397.

Heller B, Burkle A, Radons J, Fengler E, Jalowy A, Muller M, Burkart V, Kolb H: Analysis of oxygen radical toxicity in pancreatic islets at the single cell level. Biol Chem Hoppe Seyler 1994, 375:597-602.

Hirabara SM, Silveira LR, Abdulkader F, Carvalho CR, Procopio J, Curi R: Time-dependent effects of fatty acids on skeletal muscle metabolism. J Cell Physiol 2007, 210:7-15.

Huttemann M, Helling S, Sanderson TH, Sinkler C, Samavati L,
Mahapatra G, Varughese A, Lu G, Liu J, Ramzan R, et al:
Regulation of mitochondrial respiration and apoptosis through cell signaling: cytochrome c oxidase and cytochrome c in ischemia/reperfusion injury and inflammation. Biochim Biophys Acta 2012, 1817:598-609.

Jackson TM, Rawling JM, Roebuck BD, Kirkland JB: Large
supplements of nicotinic acid and nicotinamide increase tissue NAD+ and poly(ADP-ribose) levels but do not affect
diethylnitrosamine-induced altered hepatic foci in Fischer-344 rats. J Nutr 1995, 125:1455-1461.

Jacob S, Streeper RS, Fogt DL, Hokama JY, Tritschler HJ, Dietze GJ, Henriksen EJ: The antioxidant alpha-lipoic acid enhances insulin-stimulated glucose metabolism in insulin-resistant rat skeletal muscle. Diabetes 1996, 45:1024-1029.

Jacob S, Streeper RS, Fogt DL, Hokama JY, Tritschler HJ, Dietze GJ, Henriksen EJ: The antioxidant alpha-lipoic acid enhances insulin-stimulated glucose metabolism in insulin-resistant rat skeletal muscle. Diabetes 1996, 45:1024-1029.

Jang YY, Song JH, Shin YK, Han ES, Lee CS: Protective effect of boldine on oxidative mitochondrial damage in
streptozotocin-induced diabetic rats. Pharmacol Res 2000,
42:361-371.

Jezek P, Hlavata L: Mitochondria in homeostasis of reactive oxygen species in cell, tissues, and organism. Int J Biochem Cell Biol 2005, 37:2478-2503.

Johnson JJ, Petiwala SM, Syed DN, Rasmussen JT, Adhami VM,
Siddiqui IA, Kohl AM, Mukhtar H: alpha-Mangostin, a xanthone
from mangosteen fruit, promotes cell cycle arrest in prostate cancer and decreases xenograft tumor growth. Carcinogenesis 2012, 33:413-419.

Jujun P, Pootakham K, Pongpaibul Y, Duangrat C, Tharavichitkul P: Acute and Repeated Dose 28-Day Oral Toxicity Study of Garcinia mangostana Linn. Rind Extract. CMU J Nat Sci 2008, 7:199-208.

Jung HA, Su BN, Keller WJ, Mehta RG, Kinghorn AD: Antioxidant xanthones from the pericarp of Garcinia mangostana (Mangosteen). J Agric Food Chem 2006, 54:2077-2082.

Kaneto H, Nakatani Y, Kawamori D, Miyatsuka T, Matsuoka TA,
Matsuhisa M, Yamasaki Y: Role of oxidative stress, endoplasmic reticulum stress, and c-Jun N-terminal kinase in pancreatic beta-cell dysfunction and insulin resistance. Int J Biochem Cell Biol 2006, 38:782-793.

Kaneto H, Xu G, Fujii N, Kim S, Bonner-Weir S, Weir GC: Involvement of c-Jun N-terminal kinase in oxidative stress-mediated suppression of insulin gene expression. J Biol Chem 2002, 277:30010-30018.

Kristal BS, Jackson CT, Chung HY, Matsuda M, Nguyen HD, Yu BP: Defects at center P underlie diabetes-associated mitochondrial dysfunction. Free Radic Biol Med 1997, 22:823-833.

Kroncke KD, Fehsel K, Sommer A, Rodriguez ML, Kolb-Bachofen V: Nitric oxide generation during cellular metabolization of the diabetogenic N-methyl-N-nitroso-urea streptozotozin contributes to islet cell DNA damage. Biol Chem Hoppe Seyler 1995, 376:179-185.

Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, et al: Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 2006, 127:1109-1122.

Le Marchand-Brustel Y, Gual P, Gremeaux T, Gonzalez T, Barres R, Tanti JF: Fatty acid-induced insulin resistance: role of insulin receptor substrate 1 serine phosphorylation in the retroregulation of insulin signalling. Biochem Soc Trans 2003, 31:1152-1156.

Ma ZA, Zhao Z, Turk J: Mitochondrial dysfunction and beta-cell failure in type 2 diabetes mellitus. Exp Diabetes Res 2012, 2012:703538.

Mahabusarakam W, Kuaha K, Wilairat P, Taylor WC: Prenylated
xanthones as potential antiplasmodial substances. Plant Med
2006, 72:912-916.

Mahabusarakam W, Wiriyachitra P, Taylor WC: Chemical constituents of Garcinia mangostana. Journal of natural products 1987, 50:474-478.

Mahabusarakum W, Phongpaichit S, Jansakul C, Wiriyachitra P:
Screening of antibacterial activity of chemicals from Garcinia mangostana. Songklanakarin Journal of Science and Technology 1983, 5:337-339.

Martinez A, Galano A, Vargas R: Free radical scavenger properties of alpha-mangostin: thermodynamics and kinetics of HAT and RAF mechanisms. J Phys Chem B 2011, 115:12591-12598.

Masiello P, Broca C, Gross R, Roye M, Manteghetti M, Hillaire-Buys D, Novelli M, Ribes G: Experimental NIDDM: development of a new model in adult rats administered streptozotocin and nicotinamide. Diabetes 1998, 47:224-229.

Matsumoto K, Akao Y, Kobayashi E, Ohguchi K, Ito T, Tanaka T, Iinuma M, Nozawa Y: Induction of apoptosis by xanthones from mangosteen in human leukemia cell lines. J Nat Prod 2003, 66:1124-1127.

Matsumoto K, Akao Y, Yi H, Ohguchi K, Ito T, Tanaka T, Kobayashi E, Iinuma M, Nozawa Y: Preferential target is mitochondria in alpha-mangostin-induced apoptosis in human leukemia HL60 cells. Bioorg Med Chem 2004, 12:5799-5806.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF,
Turner RC: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985, 28:412-419.

Miyamoto A, Takeshita M, Pan-Hou H, Fujimori H: Hepatic changes in adenine nucleotide levels and adenosine 3''-monophosphate forming enzyme in streptozotocin-induced diabetic mice. J Toxicol Sci 2008, 33:209-217.

Moon HS, Lee HG, Choi YJ, Kim TG, Cho CS: Proposed mechanisms of (-)-epigallocatechin-3-gallate for anti-obesity. Chem Biol Interact 2007, 167:85-98.

Moongkarndi P, Kosem N, Kaslungka S, Luanratana O, Pongpan N, Neungton N: Antiproliferation, antioxidation and induction of apoptosis by Garcinia mangostana (mangosteen) on SKBR3 human breast cancer cell line. J Ethnopharmacol 2004, 90:161-166.

Moreira PI, Oliveira CR: Mitochondria as potential targets in antidiabetic therapy. Handb Exp Pharmacol 2011:331-356.

Morton JF: Fruits of Warm Climates. Miami, USA: Creative Resource Systems Inc.; 1987.

Nabandith V, Suzui M, Morioka T, Kaneshiro T, Kinjo T, Matsumoto K,

Akao Y, Iinuma M, Yoshimi N: Inhibitory effects of crude
alpha-mangostin, a xanthone derivative, on two different
categories of colon preneoplastic lesions induced by 1,
2-dimethylhydrazine in the rat. Asian Pac J Cancer Prev 2004,5:433-438.

Nakagawa Y, Iinuma M, Naoe T, Nozawa Y, Akao Y: Characterized mechanism of alpha-mangostin-induced cell death: caspase-independent apoptosis with release of endonuclease-G from mitochondria and increased miR-143 expression in human colorectal cancer DLD-1 cells. Bioorg Med Chem 2007, 15:5620-5628.

Nakatani K, Atsumi M, Arakawa T, Oosawa K, Shimura S, Nakahata N, Ohizumi Y: Inhibitions of histamine release and prostaglandin E2 synthesis by mangosteen, a Thai medicinal plant. Biol Pharm Bull 2002, 25:1137-1141.

Nakatani K, Yamakuni T, Kondo N, Arakawa T, Oosawa K, Shimura S, Inoue H, Ohizumi Y: gamma-Mangostin inhibits
inhibitor-kappaB kinase activity and decreases
lipopolysaccharide-induced cyclooxygenase-2 gene expression in C6 rat glioma cells. Mol Pharmacol 2004, 66:667-674.


Newsholme P, Gaudel C, Krause M: Mitochondria and diabetes. An intriguing pathogenetic role. Adv Exp Med Biol 2012,
942:235-247.

Newsholme P, Haber EP, Hirabara SM, Rebelato EL, Procopio J, Morgan D, Oliveira-Emilio HC, Carpinelli AR, Curi R: Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity. J Physiol 2007, 583:9-24.

Nukatsuka M, Sakurai H, Yoshimura Y, Nishida M, Kawada J:
Enhancement by streptozotocin of O2- radical generation by the xanthine oxidase system of pancreatic beta-cells. FEBS Lett 1988, 239:295-298.

Nukatsuka M, Yoshimura Y, Nishida M, Kawada J: Importance of the concentration of ATP in rat pancreatic beta cells in the mechanism of streptozotocin-induced cytotoxicity. J Endocrinol 1990a, 127:161-165.

Obolskiy D, Pischel I, Siriwatanametanon N, Heinrich M: Garcinia mangostana L.: a phytochemical and pharmacological review. Phytother Res 2009, 23:1047-1065.

Pedraza-Chaverri J, Cardenas-Rodriguez N, Orozco-Ibarra M,
Perez-Rojas JM: Medicinal properties of mangosteen (Garcinia
mangostana). Food Chem Toxicol 2008, 46:3227-3239.

Pedraza-Chaverri J, Reyes-Fermin LM, Nolasco-Amaya EG,
Orozco-Ibarra M, Medina-Campos ON, Gonzalez-Cuahutencos O,
Rivero-Cruz I, Mata R: ROS scavenging capacity and
neuroprotective effect of alpha-mangostin against
3-nitropropionic acid in cerebellar granule neurons. Exp Toxicol Pathol 2009, 61:491-501.

Perez-Gutierrez RM, Damian-Guzman M: Meliacinolin: a potent
alpha-glucosidase and alpha-amylase inhibitor isolated from
Azadirachta indica leaves and in vivo antidiabetic property in streptozotocin-nicotinamide-induced type 2 diabetes in mice. Biol Pharm Bull 2012, 35:1516-1524.

Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI: Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 2004, 350:664-671.

Petersen KF, Shulman GI: New insights into the pathogenesis of insulin resistance in humans using magnetic resonance spectroscopy. Obesity (Silver Spring) 2006, 14 Suppl 1:34S-40S.

Pothitirat W, Chomnawang MT, Gritsanapan W: Anti-acne-inducing bacterial activity of mangosteen fruit rind extracts. Med Princ Pract 2010, 19:281-286.

Remor AP, de Matos FJ, Ghisoni K, da Silva TL, Eidt G, Burigo M, de Bem AF, Silveira PC, de Leon A, Sanchez MC, et al: Differential effects of insulin on peripheral diabetes-related changes in mitochondrial bioenergetics: involvement of advanced glycosylated end products. Biochim Biophys Acta 2011, 1812:1460-1471.

Rogers KS, Friend WH, Higgins ES: Metabolic and mitochondrial disturbances in streptozotocin-treated Sprague-Dawley and Sherman rats. Proc Soc Exp Biol Med 1986, 182:167-175.

Ryu HW, Cho JK, Curtis-Long MJ, Yuk HJ, Kim YS, Jung S, Lee BW, Park KH: alpha-Glucosidase inhibition and antihyperglycemic activity of prenylated xanthones from Garcinia mangostana. Phytochemistry 2011, 72:2148-2154.

Sampath PD, Kannan V: Mitigation of mitochondrial dysfunction and regulation of eNOS expression during experimental myocardial necrosis by alpha-mangostin, a xanthonic derivative from Garcinia mangostana. Drug Chem Toxicol 2009, 32:344-352.

Scheffler IE: Mitochondria make a come back. Adv Drug Deliv Rev 2001, 49:3-26.

Shan T, Ma Q, Guo K, Liu J, Li W, Wang F, Wu E: Xanthones from mangosteen extracts as natural chemopreventive agents:
potential anticancer drugs. Curr Mol Med 2011, 11:666-677.

Shen W, Liu K, Tian C, Yang L, Li X, Ren J, Packer L, Cotman CW, Liu J: R-alpha-lipoic acid and acetyl-L-carnitine complementarily promote mitochondrial biogenesis in murine 3T3-L1 adipocytes. Diabetologia 2008, 51:165-174.

Simmons K: Defense against free radicals has therapeutic
implications. JAMA 1984, 251:2187, 2191-2182.

Simon PW: Plant Pigments for Color and Nutrition. HortScience 1997, 32:12-13.

Sornprasit A, Sripiyarattanakul K, Chauyyim P, Thanakittitham. P: Preliminary toxicological study of mangostin. Songklanakarin J Sci Technol 1987, 9:51-57.

Sousa ME, Pinto MM: Synthesis of xanthones: an overview. Curr Med Chem 2005, 12:2447-2479.

Srinivasan S, Pari L: Ameliorative effect of diosmin, a citrus flavonoid against streptozotocin-nicotinamide generated oxidative stress induced diabetic rats. Chem Biol Interact 2012, 195:43-51.

Szkudelski T: The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res 2001, 50:537-546.

Szkudelski T: Streptozotocin-nicotinamide-induced diabetes in the rat. Characteristics of the experimental model. Exp Biol Med (Maywood) 2012, 237:481-490.

Victor VM, Rocha M, Herance R, Hernandez-Mijares A: Oxidative stress and mitochondrial dysfunction in type 2 diabetes. Curr Pharm Des 2011, 17:3947-3958.

Vishnu PV, Mallika J, Mohan SK, Karthik B, Saraswathi P, Gopan VSCS: Toxicity Study of Garcinia Mangostana Linn. ASIAN J EXP BIOL SCI 2010, 1:633-637.

Wallace TM, Levy JC, Matthews DR: Use and abuse of HOMA
modeling. Diabetes Care 2004, 27:1487-1495.

Wang CH, Wang CC, Wei YH: Mitochondrial dysfunction in insulin insensitivity: implication of mitochondrial role in type 2 diabetes. Ann N Y Acad Sci 2010, 1201:157-165.

Weiss RB: Streptozocin: a review of its pharmacology, efficacy, and toxicity. Cancer Treat Rep 1982, 66:427-438.

Wohaieb SA, Godin DV: Alterations in free radical tissue-defense mechanisms in streptozocin-induced diabetes in rat. Effects of insulin treatment. Diabetes 1987, 36:1014-1018.

Zavaroni I, Sander S, Scott S, Reaven GM: Effect of fructose
feeding on insulin secretion and insulin action in the rat. Metabolism 1980, 29:970-973.

World Health Organization. (2011) Diabetes Fact sheet No 3122 2012/06/11 摘自
http://www.who.int/mediacentre/factsheets/fs312/en/

World Health Organization. Diabetes Programme About diabetes 2012/06/11 摘自
http://www.who.int/diabetes/action_online/basics/en/index1.html

行政院衛生署 食品藥物消費者知識服務網 (2011) 2005 - 2008 台灣國民營養健康狀況變遷調查結果 摘自
http://consumer.fda.gov.tw/Pages/List.aspx?nodeID=287