研究指出攝取高脂飲食會造成周邊組織胰島素阻抗，並且增加罹患第二型糖尿病及非酒精性脂肪肝的風險。消渴草(Ruellia tuberosa L.)屬於爵床科蘆莉草屬，東方國家中將之作為治療糖尿病的民間草藥。本研究探討消渴草改善高脂飲食合併STZ腹腔注射誘發之第二型糖尿病大鼠高血糖及肝臟解毒酵素系統的效果。細胞試驗方面，以33mM高葡萄糖誘導clone 9大鼠肝臟細胞株胰島素阻抗，並將消渴草水萃物或醇萃物與螢光葡萄糖2-NBDG共同培養，偵測2-NBDG的攝入量以評估抗胰島素阻抗能力；動物試驗方面，以高脂飲食合併腹腔注射STZ誘導雄性Wistar大鼠成第二型糖尿病後，每日管餵每公斤體重100或400毫克的消渴草萃取物連續4周，並評估其降血糖與改善肝臟解毒酵素的效果。結果顯示，消渴草水萃物及醇萃物分別在800mg/L的劑量下均分別可顯著地增加胰島素阻抗clone 9大鼠肝臟細胞40%及18%的葡萄糖攝入能力。消渴草水及醇萃取物均能使第二型糖尿病大鼠的血糖值、糖化血色素及果糖胺值顯著地降低，並增加肝臟中SOD、CAT和GPx抗氧化酵素的活性。聚合酶鏈鎖反應結果顯示，消渴草水萃物或醇萃物能夠對 CYP 2E1、CYP 3A2、CYP 4A2、UGT 1A7、GST M1 和 SULT 1A1顯著地恢復至正常水平。綜合以上結果，消渴草具有降低第二型糖尿病大鼠之高血糖、改善肝臟胰島素阻抗及解毒酵素系統的能力。

Studies suggest that individuals with high fat intake may adversely affect insulin resistance in the periphery tissues and result in increased risk of both Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Ruellia tuberosa L. (RTL) belongs to the Acanthaceae family. In folk medicine, it has been used for curing diabetes in East Asia. The present work was to investigate the effect of RTL on anti-hyperglycemia and detoxification enzymes system of liver in high-fat diet plus streptozotocin (STZ) induced T2DM rats. The clone 9 rat hepatocytes were treated with 33nM glucose for the induction of insulin resistance. These cells were then co-incubated with water or ethanol extract from RTL. The uptake of 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy -d-glucose (2-NBDG) in insulin-resistant clone 9 cells was used as a platform for screening extracts with the anti-insulin resistance potential. The male Wistar rats fed with high-fat diet followed by intraperitoneal injection of STZ to induced T2DM were subsequently orally administered with extract from RTL once a day at a dosage of 100 or 400 mg/kg bw for 4 weeks. The effect of RTL on anti-hyperglycemia and detoxification in T2DM rats were analyzed. The results show that water or ethanol extract from RTL (800mg/L) increases 40% and 18%, respectively, glucose uptake ability in insulin-resistant clone 9 rat hepatocytes. The plasma glucose and glycemic marker, such as HbA1C and fructosamine, levels were significantly decreased, and hepatic anti-oxidant enzymes, including SOD, CAT and GPx, activity were significantly increased in both water and ethanol extract treated T2DM rats. The results from real-time PCR analysis suggest that water or ethanol extract from RTL significantly normalized the expressions of phase I and II detoxification enzymes, including CYP 2E1, CYP 3A2, CYP 4A2, UGT 1A7, GST M1 and SULT 1A1, in T2DM rats (p< 0.05). In conclusion, RTL may alleviate hypoglycemia and hepatic insulin resistance, and ameliorate detoxification function in high-fat diet plus STZ induced T2DM rats.

Adiels, M., Taskinen, M.R., Borén, J. (2008). Fatty liver, insulin resistance, and dyslipidemia. Current Diabetes Reports. 8(1): 60-64.
Ahmed, M.H. & Byrne C.D. (2007). Modulation of sterol regulatory element binding proteins (SREBPs) as potential treatments for non-alcoholic fatty liver disease (NAFLD). Drug Discovery Today. 12(17-18): 740-747.
Allison, D.B., Fontaine, K.R., Manson, J.E., Stevens, J., VanItallie, T.B. (1999). Annual deaths attributable to obesity in the United States. Journal of the American Medical Association. 282(16): 1530-1538.
American Diabetes Association. (2004). Dyslipidemia management in adults with diabetes. Diabetes Care. 27(Suppl. 1): S68-S71.
American Diabetes Association. (2013). Diagnosis and classification of diabetes mellitus. Diabetes Care. 31: S67-74.
Andallu, B., Varadacharyulu, N.C. (2003). Antioxidant of mulberry (Morus indica L. cv. Anantha) leaves in streptozocin-diabetic rats. Clinica Chimica Acta. 338: 3-10.
Angulo, P., Keach, J.C., Batts, K.P., Lindor, K.D. (1999). Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology. 30(6): 1356-1362.
Arkan, M.C., Hevener, A.L., Greten, F.R., Maeda, S., Li, Z.W., Long, J.M., Wynshaw-Boris, A., Poli, G., Olefsky, J., Karin, M. (2005). IKK-β links inflammation to obesity-induced insulin resistance. Nature Medicine. 11(2): 191-198.
Begriche, K., Igoudjil, A., Pessayre, D., Fromenty, B. (2006). Mitochondrial dysfunction in NASH: causes, consequences and possible means to prevent it. Mitochondrion. 6(1): 1-28.
Bellentani, S., Scaglioni, F., Marino, M., Bedogni, G. (2010). Epidemiology of non-alcoholic fatty liver disease. Digestive Diseases. 28: 155-161.
Bhatia, S., Shukla, R., Madhu, S. V., Gambhir, J. K., & Prabhu, K. M. (2003). Antioxidant status, lipid peroxidation and nitric oxide end products in patients of type 2 diabetes mellitus with nephropathy. Clinical Biochemistry. 36: 557-562.
Bhatt, H.B., Smith, R.J. (2015). Fatty liver disease in diabetes mellitus. HepatoBiliary Surgery and Nutrition. 4(2): 101-108.
Boden, G., Homko, C., Mozzoli, M., Showe, L.C., Nichols, C., Cheung, P. (2005). Thiazolidinediones upregulate fatty acid uptake and oxidation in adipose tissue of diabetic patients. Diabetes. 54(3): 880-885.
Bray, G.A., Paeratakul, S., Popkin, B.M. (2004) Dietary fat and obesity: A review of animal, clinical and epidemiological studies. Physiology & Behavior. 83: 549-555.
Browning, J. D., Szczepaniak, L. S., Dobbins, R., Horton, J. D., Cohen, J. C., Grundy, S. M., Hobbs, H. H. (2004). Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 40(6): 1387-1395.
Bugianesi, E., Zannoni, C., Vanni, E., Marzocchi, R., Marchesini, G. (2004). Non-alcoholic fatty liver and insulin resistance: a cause–effect relationship?. Digestive and Liver Disease. 36(3): 165-173.
Carlsson, C., Borg, L.A., Welsh, N. (1999). Sodium palmitate induces partial mitochondrial uncoupling and reactive oxygen species in rat pancreatic islets in vitro. Endocrinology. 140: 3422-3428.
Cavaghan, M.K., Ehrmann, D.A., Polonsky, K.S. (2000). Interactions between insulin resistance and insulin secretion in the development of glucose intolerance. Journal of Clinical Investigation. 106: 329-333.
Ceriello, A. (2003). New insights on oxidative stress and diabetic complications may lead to a “causal” antioxidant therapy. Diabetes Care. 26(5): 1589-1596.
Chahil, T.J., Reyes, G., Ginsberg, H.N. (2008). Insulin Resistance and Dyslipidemia. The Metabolic Syndrome. 11:205-218.
Chalasani, N., Younossi, Z., Lavine, J.E., Diehl, A.M., Brunt, E.M., Cusi, K., Charlton, M., Sanyal, A.J. (2012). The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the american association for the study of liver diseases, american college of gastroenterology, and the american gastroenterological association. The American Journal of Gastroenterology. 55: 2005-2023.
Chang, W.C., Shen, S.C. (2013). Effect of Water Extracts from Edible Myrtaceae Plants on Uptake of 2‐(n‐(7‐nitrobenz‐2‐oxa‐1, 3‐diazol‐4‐yl) amino)‐2‐deoxyglucose in TNF‐α‐Treated FL83B Mouse Hepatocytes. Phytotherapy Research. 27(2): 236-243.
Chao, L., Marcus-Samuels, B., Mason, M.M., Moitra, J., Vinson, C., Arioglu, E., Gavrilova, O., Reitman, M.L. (2000). Adipose tissue is required for the antidiabetic, but not for the hypolipidemic, effect of thiazolidinediones. Journal of Clinical Investigation. 106: 1221-1228.
Chen, F.A., Wu, A.B., Shieh, P., Kuo, D.H., Hsieh, C.Y. (2006). Evaluation of the antioxidant of Ruellia tuberosa. Food Chemistry. 94: 14-18.
Chin, K.V., Pastan, I., Gottesman, M.M. (1993). Function and regulation of the human multidrug resistance gene. Advances in Cancer Research. 60: 157-80.
Chiu, N.Y. & Chang, K.H. (1995). The illustrated medicinal plants of Taiwan. Mingyong Medical Journal. 1:22.
Choi, S.S., Diehl, A.M. (2008). Hepatic triglyceride synthesis and nonalcoholic fatty liver disease. Current opinion in lipidology. 19(3): 295-300.
Chothani, D.L., Mishra, S.H. (2012). In vitro anti-oxidant activity of Ruellia tuberosa root extracts. Free Radicals and Antioxidants. 2(4): 38-44.
Chothani, D.L., Patel, M.B., Mishra, S.H., Vaghasiya, H.U. (2010). Review on Ruellia tuberosa (Cracker plant). Pharmacognosy Journal. 2(12): 506-512.
Chow, C.K. (1991). Vitamin E and oxidative stress. Free Radical Biology and Medicine. 11: 215-232.
Conlon, B.A., Beasley, J.M., Aebersold, K., Jhangiani, S.S., Wylie-Rosett, J. (2013). Nutritional management of insulin resistance in nonalcoholic fatty liver disease (NAFLD). Nutrients. 5(10): 4093-4114.
De Meyts, P., Whittaker, J. (2002). Structural biology of insulin and IGF1 receptors: implications for drug design. Nature Reviews Drug Discovery. 1(10): 769-783.
Defronzo, R.A., Tobin, J.D., Andres, R. (1979). Glucose clamp technique: a method for quantifying insulin secretion and resistance. American Journal of Physiology. 237: E214-223.
Del Prato, S., Enzi, G., Vigili de Kreutzenberg, S., Lisato, G., Riccio, A., Maifreni, L., Iori, E., Zurlo, F., Sergi, G., Tiengo, A. (1990). Insulin regulation of glucose and lipid metabolism in massive obesity. Diabetologia. 33(4): 228-236.
Despres, J.P., Lemieux I. (2006). Abdominal obesity and metabolic syndrome. Nature. 444: 881-887.
Dowman, J.K., Tomlinson, J.W., Newsome, P.N. (2010). Pathogenesis of non-alcoholic fatty liver disease. Quarterly Journal of Medicine. 103(2): 71-83.
Gandhi, A., Ghose, R. (2012). Altered drug metabolism and transport in pathophysiological conditions. Topics on Drug Metabolism. 5: 111-136.
Ghosh, S., Dey, S. (2011). Pioglitazone induced weight changes in type 2 diabetic patients. International Journal of Collaborative Research on Internal Medicine & Public Health. 3(6): 534-540.
Ginsberg, H., Kimmerling, G., Olefsky, J.M., Reaven, G.M. (1975). Demonstration of insulin resistance in untreated adult onset diabetic subjects with fasting hyperglycemia. Journal of Clinical Investigation. 55: 454-461.
Haffner, S.M. (1998). Management of dyslipidemia in adults with diabetes (Technical review). Diabetes Care. 21: 160-178.
Haring, R., Wallaschofski, H., Nauck, M., Dörr, M., Baumeister, S.E., Völzke, H. (2009). Ultrasonographic hepatic steatosis increases prediction of mortality risk from elevated serum gamma-glutamyl transpeptidase levels. Hepatology. 50(5): 1403–1411.
Hines, R.N., McCarver, D.G. (2002). The ontogeny of human drug-metabolizing enzymes: phase I oxidative enzymes. Journal of Pharmacology and Experimental Therapeutics. 300(2): 355-360.
Houstis, N., Rosen, E.D., Lander, E.S. (2006). Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature. 440(7086): 944-948.
International Diabetes Federation. IDF Diabetes Atlas (6th edition). 2013.
Ji, G., Zhao, X., Leng, L., Liu, P., Jiang, Z. (2011). Comparison of dietary control and atorvastatin on high fat diet induced hepatic steatosis and hyperlipidemia in rats. Lipids in Health and Disease. 10: 23-33.
Ji, G., Zhao, X., Leng, L., Liu, P., Jiang, Z. (2011). Comparison of dietary control and atorvastatin on high fat diet induced hepatic steatosis and hyperlipidemia in rats. Lipids in Health and Disease. 10(1): 23-32.
Jiang, G., Dallas-Yang, Q., Li, Z., Szalkowski, D., Liu, F., Shen, X., Wul, M., Zhoul, G., Doebberl, T., Bergerl, J., Mollerl, D.E., Zhang, B.B. (2002). Potentiation of insulin signaling in tissues of Zucker obese rats after acute and long-term treatment with PPARγ agonists. Diabetes. 51(8): 2412-2419.
Jiang, Y.D., Chang, C.H., Tai, T.Y., Chen, J.F., Chuang, L.M. (2012). Incidence and prevalence rates of diabetes mellitus in Taiwan: analysis of the 2000-2009 Nationwide Health Insurance database. Journal of the Formosan Medical Association. 111(11): 587-664.
Jones, A.G., Hattersley, A.T. (2013). The clinical utility of C‐peptide measurement in the care of patients with diabetes. Diabetic Medicine. 30(7): 803-817.
Joshi, S.R., Parikh, R.M., Das, A.K. (2007). Insulin: history, biochemistry, physiology and pharmacology. Journal of the Association of Physicians of India. 55(suppl): 19-25.
Kahn, B.B., Flier, J.S. (2000). Obesity and insulin resistance. The Journal of Clinical Investigation. 106(4): 473-481.
Katz, A., Nambi, S.S., Mather, K., Baron, A.D., Follmann, D.A., Sullivan, G., Quon, M.J. (2000). Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. The Journal of Clinical Endocrinology & Metabolism. 85(7): 2402-2410.
Kew, M.C. (2000). Serum aminotransferase concentration as evidence of hepatocellular damage. Lancet. 355(9204): 591-592.
Klaassen, C.D., Lu, H. (2008). Xenobiotic transporters: ascribing function from gene knockout and mutation studies. Toxicological Sciences. 101(2): 186-196.
Kotronen, A., Yki-Järvinen, H. (2008). Fatty liver: a novel component of the metabolic syndrome. Arterioscler. Thromb. Vascular Biology. 28: 27-38.
Krishna, C.B., Bavindra B.S., Ramesh, C.A.R., Jayasree, V., Diana V.A. (2012). Hypolipidemic and antioxidant activity of Ruellia tuberosa Linn. International Journal of pharma and bio sciences. 2(3): 63-72.
Laffel, L. (1999). Ketone Bodies: a Review of Physiology, Pathophysiology and Application of Monitoring to Diabetes. Diabetes/Metabolism Research and Reviews. 15(6): 412-426.
Lalli, C. A., Pauli, J. R., Prada, P. O., Cintra, D. E., Ropelle, E. R., Velloso, L. A., Saad, M. J. (2008). Statin modulates insulin signaling and insulin resistance in liver and muscle of rats fed a high-fat diet. Metabolism. 57: 57-65.
Leclercq, I.A., Da Silva Morais, A., Schroyen, B., Van Hul, N., Geerts, A. (2007). Insulin resistance in hepatocytes and sinusoidal liver cells: mechanisms and consequences. Journal of Hepatology. 47(1): 142-156.
Lee, C.C., Hsu, W.H., Shen, S.R., Cheng, Y.H., Wu, S.C. (2012). Fagopyrum tataricum (buckwheat) improved high-glucose-induced insulin resistance in mouse hepatocytes and diabetes in fructose-rich diet-induced mice. Experimental Diabetes Research. 2012: 1-10.
Lewis, J.R., Mohanty, S.R. (2010). Nonalcoholic fatty liver disease: a review and update. Digestive Diseases and Sciences. 55(3): 560-578.
Li, J., Ma, W., Wang, S. (2011). Slower gastric emptying in high-fat diet induced obese rats is associated with attenuated plasma ghrelin and elevated plasma leptin and cholecystokinin concentrations. Regulatory Peptides. 171(1-3): 53-57.
Limón-Pacheco, J., Gonsebatt, M.E. (2009). The role of antioxidants and antioxidant-related enzymes in protective responses to environmentally induced oxidative stress. Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 674(1): 137-147.
Lin, C.L., Lin, J.K. (2008). Epigallocatechin gallate (EGCG) attenuates high glucose‐induced insulin signaling blockade in human hepG2 hepatoma cells. Molecular Nutrition & Food Research. 52(8): 930-939.
Lin, C.F., Huang, Y.L., Cheng, L.Y., Sheu, S.J., Chen, C.C. (2006). Bioactive flavonoids from Ruellia tuberosa. Journal of the Chinese Medical Association. 17(3): 103-109.
Lin, J., Sahakian, D.C.,de Morais, S.M., Xu, J.J., Polzer, R.J., Winter, S.M. (2003). The role of absorption, distribution, metabolism, excretion and toxicity in drug discovery. Current Topics in Medicinal Chemistry. 3(10): 1125-1154.
Liska, D.J. (1998). The detoxification enzyme systems. Alternative Medicine Review. 3(3): 187-198.
Liu, Q., Bengmark, S., Qu, S. (2010). Review The role of hepatic fat accumulation in pathogenesis of non-alcoholic fatty liver disease (NAFLD). Lipids in Health and Disease. 9, 42~50.
Louzao, M.C., Espiña, B., Vieytes, M.R., Vega, F.V., Rubiolo, J.A., Baba, O., Botana, L.M. (2008). “Fluorescent glycogen” formation with sensibility for in vivo and in vitro detection. Glycoconjugate Journal. 25(6): 503-510.
Ma, H., You, G.P., Zhang, X.P., Yang, X.J., Lu, H.D., Huang, Y. L., Zhang, W.Q. (2014). A novel role of globular adiponectin in treatment with HFD/STZ induced T2DM combined with NAFLD rats. The Scientific World Journal. 2014: 1-7.
Malekinejad, H., Rezabakhsh, A., Rahmani, F., Hobbenaghi, R. (2012). Silymarin regulates the cytochrome P450 3A2 and glutathione peroxides in the liver of streptozotocin-induced diabetic rats. Phytomedicine. 19(7): 583-590.
Manikandan, A. & Victor Arokia Doss, D. (2010). Effect of 50% Hydroethanolic Leaf Extracts of Ruellia tuberosa Linn and Dipteracanthus patulus (Jacq.) on Non-enzymic Antioxidants and other Biochemical Parameters in Liver, Kidney, Serum of Alloxan Induced Diabetic Swiss Albino Rats. Journal of Biomedical Sciences and Research. 2(3): 190-201.
Marchesini, G., Brizi, M., Marsell-Labate, A.M., Bianchi, G., Buqianesi, E., Mccullough, A.J., Forlani, C., Melchionda, N. (1999). Association of nonalcoholic fatty liver disease with insulin resistance. American Journal of Medicine. 107: 450-455.
Mari, A., Ahrén, B., Pacini, G. (2005). Assessment of insulin secretion in relation to insulin resistance. Current Opinion in Clinical Nutrition and Metabolic Care. 8(5): 529-533.
Martino, V., Morales, J., Martinez-Irujo, J.J., Font, M., Mouge, A., Coussio, J. (2004). Two ellagitannins from the leaves of Terminalia triglora with ingibitory activity on HIV-1 reverse transcriptase. Phytotherapy Research. 18: 667-669.
Matthews, D.R., Hosker, J.P., Rudenski, A.S., Naylor, B.A., Treacher, D.F., Turner, R.C. (1985). Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 28(7): 412-419.
McCarver, D.G., Hines, R.N. (2002). The ontogeny of human drug-metabolizing enzymes: phase II conjugation enzymes and regulatory mechanisms. Journal of Pharmacology and Experimental Therapeutics. 300(2): 361-366.
McGarry, J.D. (1992). What if Minkowski had been ageusic? An alternative angle on diabetes. Science. 258(5083): 766-770.
McGarry, J.D. (2002). Dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes. 51: 7-18.
Merrell, M.D., Cherrington, N.J. (2011). Drug metabolism alterations in nonalcoholic fatty liver disease. Drug Metabolism Reviews. 43(3): 317-334.
Milani, E., Nikfar, S., Khorasani, R., Zamani, M. J., Abdollahi, M. (2005). Reduction of diabetes-induced oxidative stress by phosphodiesterase inhibitors in rats. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology. 140: 251-255.
Naik, A., Belič, A., Zanger, U.M., Rozman, D. (2013). Molecular interactions between NAFLD and xenobiotic metabolism. Frontiers in Genetics. 4(2):1-14.
Nawano, M., Ueta, K., Oku, A., Arakawa, K., Saito, A., Funakic, M., Anaia, M., Kikuchic, M., Okad, Y. & Asanoa, T. (1999). Hyperglycemia impairs the insulin signaling step between PI 3-kinase and Akt/PKB activations in ZDF rat liver. Biochemical and Biophysical Research Communications. 266(1): 252-256.
Nebert, D. W. & Russell, D. W. (2002). Clinical importance of the cytochromes P450. The Lancet. 360(9340), 1155-1162.
Neuschwander-Tetri, B.A., Caldwell, S.H. (2003). Nonalcoholic steatohepatitis: summary of an AASLD single topic conference. Hepatology. 37(5): 1202-1219.
Novo, E., Parola, M. (2008). Redox mechanisms in hepatic chronic wound healing and fibrogenesis. Fibrogenesis Tissue Repair. 1: 5~62.
Obika, M., Noguchi, H. (2011). Diagnosis and evaluation of nonalcoholic fatty liver disease. Experimental Diabetes Research. 2012: 1-12.
Oh, K.B., Matsuoka, H. (2002). Rapid viability assessment of yeast cells using vital staining with 2-NBDG, a fluorescent derivative of glucose. International Journal of Food Microbiology. 76(1): 47-53.
Okabayashi, Y., Maddux, B.A., Mcdonald, A.R., Logsdon, C.D., Williams, J.A., Goldfine, I.D. (1989). Mechanisms of insulin-induced insulin-receptor downregulation : decrease of receptor biosynthesis and mRNA levels. Diabetes. 38: 182-187.
Paolisso, G., Gambardella, A., Tagliamonte, M.R., Saccomanno, F., Salvatore, T., Gualdiero, P., D’Onofrio, M.V., Howard, B.V. (1996). Does free fatty acid infusion impair insulin action also through an increase in oxidative stress?. The Journal of Clinical Endocrinology & Metabolism. 81(12): 4244-4248.
Paschos, P., Paletas, K. (2009). Non alcoholic fatty liver disease and metabolic syndrome. Hippokratia. 13(1): 9~19.
Percival, M. (1997). Phytonutrients and detoxification. Clinical Nutrition Insights. 5(2): 1-4.
Petersen, K.F., Shulman, G.I. (2006). Etiology of insulin resistance. American Journal of Medicine. 119(1): S10-S16.
Puigserver, P., Rodgers, J.T. (2006). Foxa2, a novel transcriptional regulator of insulin sensitivity. Nature. 12: 38-39.
Qatanani, M., Lazar, M.A. (2007). Mechanisms of obesity-associated insulin resistance: many choices on the menu. Genes & Development. 21: 1443-1455.
Rajan, M., Kumar, V.K., Kumar, P.S., Swathi, K.R., Haritha, S. (2012). Antidiabetic, antihyperlipidaemic and hepatoprotective activity of methanolic extract of Ruellia tuberosa. Linn leaves in normal and alloxan induced diabetic rats. Journal of Chemical and Pharmaceutical Research. 4(6): 2860-8.
Rangwala, S.M., Lazar, M.A. (2004). Peroxisome proliferator-activated receptor γ in diabetes and metabolism. Trends in Pharmacological Sciences. 25: 331-336.
Rao, G. (2001). Insulin resistance syndrome. American Family Physician. 63(6): 1159-1166.
Ratziu, V., Bellentani, S., Cortez-Pinto, H., Day, C., Marchesini, G. (2010). A position statement on NAFLD/NASH based on the EASL 2009 special conference. Journal of Hepatology. 53(2): 372-384.
Reaven, G.M. (1995). Pathophysiology of insulin resistance in human disease. Physiological Reviews. 75: 473-486.
Riddle, M.C. (1997). Tactics for type 2 diabetes. Journal of Clinical Endocrinology & Metabolism. 26: 659-677.
Robertson, G., Leclercq, I., Farrell, G.C. (2001). II. Cytochrome P-450 enzymes and oxidative stress. American Journal of Physiology-Gastrointestinal and Liver Physiology. 281(5): G1135-G1139.
Rösen, P., Nawroth, P.P., King, G., Möller, W., Tritschler, H.J., Packer, L. (2001). The role of oxidative stress in the onset and progression of diabetes and its complications: asummary of a Congress Series sponsored byUNESCO‐MCBN, the American Diabetes Association and the German Diabetes Society. Diabetes/Metabolism Research and Reviews. 17(3): 189-212.
Rössner, S.M., Neovius, M., Mattsson, A., Marcus, C., Norgren, S. (2010). HOMA‐IR and QUICKI: decide on a general standard instead of making further comparisons. Acta Paediatrica. 99(11): 1735-1740.
Saltiel, A.R. (2000). The molecular and physiological basis of insulin resistance. Journal of Clinical Investigation. 106: 163-164.
Saltiel, A.R., Kahn, C.R. (2001). Insulin signalling and the regulation of glucose and lipid metabolism. Nature. 414(6865): 799-806.
Samuel, V.T., Shulman, G.I. (2012). Mechanisms for insulin resistance: common threads and missing links. Cell. 148(5): 852-871.
Sanyal, A.J., Brunt, E.M., Kleiner, D.E., Kowdley, K.V., Chalasani, N., Lavine, J.E., Ratziu, V., McCullough, A. (2011). Endpoints and clinical trial design for nonalcoholic steatohepatitis. Hepatology. 54: 344-353.
Sarafidis, P.A., Lasaridis, A.N., Nilsson, P.M., Pikilidou, M.I., Stafilas, P.C., Kanaki, A., Kazakos, K., Yovos, J., Bakris, G.L. (2007). Validity and reproducibility of HOMA-IR, 1/HOMA-IR, QUICKI and McAuley's indices in patients with hypertension and type II diabetes. Journal of Human Hypertension. 21(9): 709-716.
Sargent, J.M. (2003). The use of the MTT assay to study drug resistance in fresh tumour samples. Chemosensitivity Testing in Oncology. Springer Berlin Heidelberg. 161:13-25.
Seghrouchni, I., Drai, J., Bannier, E., Riviere, J., Calmard, P., Garcia, I., Orgiazzi, J., Revol, A. (2003). Oxidative stress parameters in type I, type II and insulin-treated type 2 diabetes mellitus, insulin treatment efficiency. Clinica Chimica Acta. 321: 89-96.
Sekeroglu, M.R., Sahin, H., Dulger, H., Algun, E. (2003). The effect of dietary treatment on erythrocyte lipid peroxidation, superoxide dismutase, glutathione peroxidase, and serum lipid peroxidation in patients with type 2 diabetes mellitus. Clinical Biochemistry. 33: 669-674.
Shepherd, P.R., Kahn, B.B. (1999). Glucose transporters and insulin action: implications for insulin resistance and diabetes mellitus. The New England Journal of Medicine. 341: 248-257.
Sindhu, R.K., Koo, J.R., Sindhu, K.K., Ehdaie, A., Farmand, F., Roberts, C.K. (2006). Differential regulation of hepatic cytochrome P450 monoxygenases in streptozotocin-induced diabetic rats. Free Radical Research. 40: 921-928.
Sozio, M.S., Liangpunsakul, S. & Crabb, D. (2010). The role of lipid metabolism in the pathogenesis of alcoholic and nonalcoholic hepatic steatosis. Seminars in Liver Disease. 30(4): 378-390.
Stefan, N., Häring, H.U. (2011). The metabolically benign and malignant fatty liver. Diabetes. 60: 2011-2017.
Targher, G., Bertolini, L., Poli, F., Rodella, S., Scala, L., Tessari, R., Scala1, L., Tessari1, R., Zenari1, L., Falezza, G. (2005). Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Diabetes. 54(12): 3541-3546.
Unger, R.H., Orci, L. (2000). Lipotoxic diseases of nonadipose tissues in obesity. International Journal of Obesity and Related Metabolic Disorders. 24: S28-S32.
Vornoli, A., Pozzo, L., Della Croce, C.M., Gervasi, P.G., Longo, V. (2014). Drug metabolism enzymes in a steatotic model of rat treated with a high fat diet and a low dose of streptozotocin. Food and Chemical Toxicology. 70: 54-60.
World Health Organization. (2014). http://www.who.int/mediacentre/factsheets/fs138/en/
Wu, K.K., Huan, Y. (2008). Streptozotocin‐induced diabetic models in mice and rats. Current Protocols in Pharmacology. p.5-47.
Yoshioka, K., Oh, K.B., Saito, M., Nemoto, Y., Matsuoka, H. (1996). Evaluation of 2-[N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino]-2-deoxy-D-glucose, a new fluorescent derivative of glucose, for viability assessment of yeast Candida albicans. Applied Microbiology and Biotechnology. 46(4): 400-404.
Youngren, J.F.; Paik, J.; Barnard, R.J. (2001). Impaired insulin-receptor autophosphorylation is an early defect in fat-fed, insulin-resistant rats. Journal of Applied Physiology. 91: 2240-2247.
Zechner, R., Strauss, J.G., Haemmerle, G., Lass, A., Zimmermann, R. (2005). Lipolysis: pathway under construction. Current Opinion in Lipidology. 16(3): 333-340.
Zeng, M.D., Fan, J.G., Lu, L.G., Li, Y.M., Chen, C.W., Wang, B.Y., Mao, Y.M. (2008). Guidelines for the diagnosis and treatment of nonalcoholic fatty liver diseases. Journal of Digestive Diseases. 9(2): 108-112.
Zierath, J.R., Livingston, J.N., Thörne, A., Bolinder, J., Reynisdottir, S., Lönnqvist, F., Arner, P. (1998). Regional difference in insulin inhibition of non-esterified fatty acid release from human adipocytes: relation to insulin receptor phosphorylation and intracellular signalling through the insulin receptor substrate-1 pathway. Diabetologia. 41(11): 1343-1354.
Zou, C., Wang, Y., Shen, Z. (2005). 2-NBDG as a fluorescent indicator for direct glucose uptake measurement. Journal of Biochemical and Biophysical Methods. 64(3): 207-215.
王長君、王仁潔、張麗姿、殷鳳儀、史中、王嘉詮、劉念先、馬國興、趙壯飛、徐佳福、鄭瓊娟、蔡元榮和吳慶祥。(2006)。ROSS組織學。合記圖書出版社。576-91頁。
吳青蓉。(2011)。黃金銀耳酸性多醣對FL83B小鼠肝臟細胞具胰島素增敏功效。碩士論文，東海大學食品科學研究所。
邱年永。(2008)。原色台灣藥用植物圖鑑-第5冊。南天書局。212頁。
柯文馨、胡明一、黃雍協、廖克剛和劉春蘭編譯。(2008)。WHEATER’S功能性組織學。台灣愛思唯爾有限公司。288-97頁。
許桂森、林明忠、蕭哲志。(2001)。簡明圖解藥理學。藝軒圖書出版社。17-19頁。
陳國群。(1999)。糖尿病治療藥物。藝軒圖書出版社。1-5頁。
麥麗敏、王如玉、陳淑瑩、薛宇哲、林淑玟、陳瑩玲、沈賈堯和郭純琦。(1996)。新編生理學。永大書局有限公司。59-62頁。
廖婉琦。(2012)。荖葉對肝臟解毒酵素基因表現之影響。碩士論文，中山醫學大學生化暨生物科技研究所。
樓迎統、陳君侃、黃榮棋、王錫五。(2005)。生理學。偉華書局有限公司。240-247頁。
衛生福利部國民健康署統計。歷年糖尿病盛行率。(2013)。http://www.hpa.gov.tw/BHPNet/Web/HealthTopic/TopicArticle.aspx?No=201410060012&parentid=201410030001
衛生福利部統計處。國人十大死因。(2015)。http://www.mohw.gov.tw/cht/DOS/Statistic.aspx?f_list_no=312&fod_list_no=54