近來研究證實第二型糖尿病(T2DM)與非酒精性脂肪肝(NAFLD)之間有相當大的關聯性，T2DM胰島素阻抗導致的肝臟NLRP3發炎體活化可能與脂肪堆積有關。α-硫辛酸(ALA)已被報導可改善T2DM大鼠胰島素阻抗和肝臟發炎。本研究探討ALA對高脂飲食(HFD)及鍊脲佐菌素(STZ)誘發T2DM大鼠肝臟中NLRP3發炎體活化、胰島素阻抗及脂肪堆積的影響。八周大的雄性Wistar大鼠以HFD (60%脂肪)餵養4周後，腹腔注射(ip)低劑量STZ (30mg/kg bw)並繼續餵食HFD巴已以後成功誘導第二型糖尿病，之後每日管餵ALA (50、100、200 mg/kg bw) 13周後，犧牲大鼠並採集血液進行分析、以西方墨點法(Western blot)測量大鼠肝臟胰島素阻抗、NLRP3發炎體相關蛋白質、細胞激素IL-1β及脂肪代謝相關蛋白質表現量，並檢測肝臟中三酸甘油酯(TG)的濃度。結果顯示，給予ALA 50、100、200 mg/kg bw處理能夠顯著降低HFD/STZ誘導T2DM大鼠肝臟之TG含量，與DM組相比分別降低61.8%、71.1%、64.7%。此外，給予ALA 200mg/kg bw能夠顯著提升T2DM大鼠肝臟胰島素傳訊相關路徑蛋白質PI3K以及pAkt/Akt表現量170.3%、100.3%，並降低肝臟NLRP3發炎體上游之NLRP3蛋白71.1%、降低下游caspase-1、IL-1β蛋白表現量52.3%、34.21%和降低脂肪合成相關蛋白質SREBP-1c之表現量48.1%、並增加脂肪氧化酵素CPT-1表現量47.1%此外，給予ALA 200mg/kg bw能夠顯著提升T2DM大鼠肝臟胰島素傳訊相關路徑蛋白質PI3K以及pAkt/Akt表現量170.3%、100.3%，並降低肝臟NLRP3發炎體上游之NLRP3蛋白71.1%、降低下游caspase-1、IL-1β蛋白表現量52.3%、34.21%和降低脂肪合成相關蛋白質SREBP-1c之表現量48.1%、並增加脂肪氧化酵素CPT-1表現量47.1%。歸納上述研究結果，給予ALA處理能夠改善HFD/STZ誘導T2DM大鼠肝臟胰島素阻抗、發炎體活化及脂肪堆積之惡性循環。本實驗結果可作為未來評估ALA開發為預防糖尿病所引發NAFLD合併症的膳食補充劑或保健食品之參考。

Recently studies suggested that there is correlation between type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD). Liver NLRP3 inflammasome activation caused by insulin resistance may be associated with fat accumulation. Alpha-lipoic acid (ALA) has been reported to improve insulin resistance and reduce liver inflammation in T2DM rats. The present work was to investigate the effects of ALA on NLRP3 inflammasome activation, insulin resistance and fat accumulation of liver in high-fat diet plus streptozotocin (STZ) induced T2DM rats. Male Wistar rats fed with HFD (60% fat) for 4 weeks, and intraperitoneal (ip) low-dose STZ (30 mg/kg bw) and continued feeding of HFD until induced type 2 diabetes. After 13 weeks of feeding ALA (50, 100, 200 mg/kg bw), the rats were sacrificed and blood was collected for analysis. The insulin resistance, NLRP3 inflammasome related protein in liver was measured by Western blot. The content of IL-1β and the concentration of triglyceride (TG) in the liver was measured. The results showed that treatment with ALA 50, 100, 200 mg/kg bw significantly reduced the TG content in the liver of T2DM rats induced by HFD/STZ, which was 61.8%, 71.1%, and 64.7% lower than the DM group. In addition, the group of ALA 200mg/kg bw significantly increased the protein expression of PI3K and pAkt/Akt in the liver compared with DM rats which take up 170.3%, 100.3%, and decreased the NLRP3 inflammasome relative protein NLRP3, caspase-1, IL-1β expression by 71.1%, 52.3% and 34.21%. The expression of SREBP-1c, a protein related to fat synthesis, was decreased by 48.1%, and the expression of CPT-1 was increased by 47.1%. In conclusion, ALA treatment alleviated the hepatic insulin resistance, inflammasome activation and fat accumulation in HFD/STZ-induced T2DM rats. The results of this study suggest ALA as a health supplements in NAFLD complications caused by diabetes.

陳文英。(2009)。鉻對胰島素訊息傳遞及肝損傷之研究。中興大學獸醫學系暨研究所學位論文，pp.1-71。
涂孟萱(2017)。硫辛酸抑制NLRP3發炎體活化而減緩高脂飲食及STZ誘發第二型糖尿病大鼠內臟脂肪組織發炎反應之研究。國立台灣師範大學碩士論文位論文。
Abdelhalim, M. A. K., Moussa, S. A. A., Qaid, H. A., & Al-Ayed, M. S. (2018). Potential effects of different natural antioxidants on inflammatory damage and oxidative-mediated hepatotoxicity induced by gold nanoparticles. International Journal of Nanomedicine, 13, 7931.
Arumugam, M., Raes, J., Pelletier, E., Le Paslier, D., Yamada, T., Mende, D. R. & Bertalan, M. (2011). Enterotypes of the human gut microbiome. Nature, 473(7346), 174.
Avruch, J. (1998). Insulin signal transduction through protein kinase cascades. In Insulin Action (pp. 31-48). Springer, Boston, MA.
Bangalore, S., Fayyad, R., DeMicco, D. A., Colhoun, H. M., & Waters, D. D. (2018). Body Weight Variability and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus. Circulation: Cardiovascular Quality and Outcomes, 11(11), e004724.
Bast, A., & Haenen, G. R. (2003). Lipoic acid: a multifunctional antioxidant. Biofactors, 17(1‐4), 207-213.
Bergman, R. N., & Ader, M. (2000). Free fatty acids and pathogenesis of type 2 diabetes mellitus. Trends in Endocrinology & Metabolism, 11(9), 351-356.
Biddinger, S. B., Hernandez-Ono, A., Rask-Madsen, C., Haas, J. T., Alemán, J. O., Suzuki, R& Cohen, D. E. (2008). Hepatic insulin resistance is sufficient to produce dyslipidemia and susceptibility to atherosclerosis. Cell metabolism, 7(2), 125-134.
Botros, M., & Sikaris, K. A. (2013). The de ritis ratio: the test of time. The Clinical Biochemist Reviews, 34(3), 117.
Brown, M. S., & Goldstein, J. L. (2008). Selective versus total insulin resistance: a pathogenic paradox. Cell metabolism, 7(2), 95-96.
Buzzetti, E., Pinzani, M., & Tsochatzis, E. A. (2016). The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism, 65(8), 1038-1048.
Szabo, G., & Csak, T. (2012). Inflammasomes in liver diseases. Journal of Hepatology, 57(3), 642-654.
Cai, D., Yuan, M., Frantz, D. F., Melendez, P. A., Hansen, L., Lee, J., & Shoelson, S. E. (2005). Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB. Nature Medicine, 11(2), 183.
Camell, C. D., Nguyen, K. Y., Jurczak, M. J., Christian, B. E., Shulman, G. I., Shadel, G. S., & Dixit, V. D. (2015). Macrophage-specific de novo synthesis of ceramide is dispensable for inflammasome-driven inflammation and insulin resistance in obesity. Journal of Biological Chemistry, 290(49), 29402-29413.
Castro, M. C., Villagarcía, H. G., Massa, M. L., & Francini, F. (2018). Alpha-lipoic acid and its protective role in fructose induced endocrine-metabolic disturbances. Food & Function.
Camporez, J. P. (2016). Disruption of adipose Rab10-dependent insulin signaling causes hepatic insulin resistance. Diabetes, 65(6), 1577-1589.
Chalasani, N., Younossi, Z., Lavine, J. E., Diehl, A. M., Brunt, E. M., Cusi, K& 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. Hepatology, 55(6), 2005-2023.
Chao, H. W., Chao, S. W., Lin, H., Ku, H. C., & Cheng, C. F. (2019). Homeostasis of glucose and lipid in non-alcoholic fatty liver disease. International journal of molecular sciences, 20(2), 298.
Chen, K., Feng, L., Hu, W., Chen, J., Wang, X., Wang, L., & He, Y. (2018). Optineurin inhibits NLRP3 inflammasome activation by enhancing mitophagy of renal tubular cells in diabetic nephropathy. The FASEB Journal, fj-201801749RRR.
Donath, M. Y., & Shoelson, S. E. (2011). Type 2 diabetes as an inflammatory disease. Nature Reviews Immunology, 11(2), 98.
Festi, D., Colecchia, A., Sacco, T., Bondi, M., Roda, E., & Marchesini, G. (2004). Hepatic steatosis in obese patients: clinical aspects and prognostic significance. Obesity Reviews, 5(1), 27-42.
Fève, B., & Bastard, J. P. (2009). The role of interleukins in insulin resistance and type 2 diabetes mellitus. Nature Reviews Endocrinology, 5(6), 305.
Fu, Z., R Gilbert, E., & Liu, D. (2013). Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Current diabetes reviews, 9(1), 25-53.
Godoy, P., Hewitt, N. J., Albrecht, U., Andersen, M. E., Ansari, N., Bhattacharya, S & Braeuning, A. (2013). Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME. Archives of toxicology, 87(8), 1315-1530.
Gomes, M. B., & Negrato, C. A. (2014). Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases. Diabetology & metabolic syndrome, 6(1), 80.
Grundy, S. M. (2004). Obesity, metabolic syndrome, and cardiovascular disease. The Journal of Clinical Endocrinology & Metabolism, 89(6), 2595-2600.
Guilherme, A., Virbasius, J. V., Puri, V., & Czech, M. P. (2008). Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nature Reviews Molecular Cell Biology, 9(5), 367.
Han, D., Handelman, G., Marcocci, L., Sen, C. K., Roy, S., Kobuchi, H & Packer, L. (1997). Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. Biofactors, 6(3), 321-338
Han, J. W., Zhan, X. R., Li, X. Y., Xia, B., Wang, Y. Y., Zhang, J., & Li, B. X. (2010). Impaired PI3K/Akt signal pathway and hepatocellular injury in high-fat fed rats. World Journal of Gastroenterology: WJG, 16(48), 6111.
HAPO Study Cooperative Research Group. (2008). Hyperglycemia and adverse pregnancy outcomes. New England Journal of Medicine, 358(19), 1991-2002.
He, K., Zhu, X., Liu, Y., Miao, C., Wang, T., Li, P & Li, J. (2017). Inhibition of NLRP3 inflammasome by thioredoxin-interacting protein in mouse Kupffer cells as a regulatory mechanism for non-alcoholic fatty liver disease development. Oncotarget, 8(23), 37657.
He, Q., Gao, Z., Yin, J., Zhang, J., Yun, Z., & Ye, J. (2011). Regulation of HIF-1α activity in adipose tissue by obesity-associated factors: adipogenesis, insulin, and hypoxia. American Journal of Physiology-Endocrinology and Metabolism, 300(5), E877-E885.
Hotamisligil, G. S. (2010). Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell, 140(6), 900-917.
Hou, J. C., Min, L., & Pessin, J. E. (2009). Insulin granule biogenesis, trafficking and exocytosis. Vitamins & Hormones, 80, 473-506.
Huang, X., Liu, G., Guo, J., & Su, Z. (2018). The PI3K/AKT pathway in obesity and type 2 diabetes. International journal of biological sciences, 14(11), 1483.
Huang, Y., Jiang, H., Chen, Y., Wang, X., Yang, Y., Tao, J& Zhou, R. (2018). Tranilast directly targets NLRP3 to treat inflammasome‐driven diseases. EMBO molecular medicine, 10(4), e8689.
Imaeda, A. B., Watanabe, A., Sohail, M. A., Mahmood, S., Mohamadnejad, M., Sutterwala, F. S & Mehal, W. Z. (2009). Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome. The Journal of Clinical Investigation, 119(2), 305-314.
Inoue, M., & Shinohara, M. L. (2013). Nlrp3 inflammasome and MS/EAE. Autoimmune Diseases, 2013.
Jiang, C., Xie, C., Li, F., Zhang, L., Nichols, R. G., Krausz, K. W& Tanaka, N. (2015). Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease. The Journal of clinical investigation, 125(1), 386-402.
Kietzmann, T., Dimova, E. Y., Flügel, D., & Scharf, J. G. (2006). Oxygen: modulator of physiological and pathophysiological processes in the liver. Zeitschriftfür Gastroenterologie, 44(01), 67-76.
Kim, M. S., Jo, D. S., & Lee, D. Y. (2018). Comparison of HbA1c and OGTT for the Diagnosis of Type 2 Diabetes in Children at Risk of Diabetes. Pediatrics & Neonatology.
Kmiec, Z. (2001). Cooperation of liver cells in health and disease: with 18 tables (Vol. 161). Springer Science & Business Media.
Kotronen, A., & Yki-Järvinen, H. (2008). Fatty liver: a novel component of the metabolic syndrome. Arteriosclerosis, thrombosis, and vascular biology, 28(1), 27-38.
Kummer, J. A., Broekhuizen, R., Everett, H., Agostini, L., Kuijk, L., Martinon, F & Tschopp, J. (2007). Inflammasome components NALP 1 and 3 show distinct but separate expression profiles in human tissues suggesting a site-specific role in the inflammatory response. Journal of Histochemistry & Cytochemistry, 55(5), 443-452.
Kuwabara, W. M. T., Panveloski-Costa, A. C., Yokota, C. N. F., Pereira, J. N. B., Mancini Filho, J., Torres, R. P., & Alba-Loureiro, T. C. (2017). Comparison of Goto-Kakizaki rats and high fat diet-induced obese rats: Are they reliable models to study Type 2 Diabetes mellitus?. PloS one, 12(12), e0189622.
Larter, C. Z., Chitturi, S., Heydet, D., & Farrell, G. C. (2010). A fresh look at NASH pathogenesis. Part 1: the metabolic movers. Journal of gastroenterology and hepatology, 25(4), 672-690.
Leahy, J. L., Cooper, H. E., Deal, D. A & Weir, G. C. (1986). Chronic hyperglycemia is associated with impaired glucose influence on insulin secretion. A study in normal rats using chronic in vivo glucose infusions. The Journal of clinical investigation, 77(3), 908-915
Leamy, A. K., Egnatchik, R. A., & Young, J. D. (2013). Molecular mechanisms and the role of saturated fatty acids in the progression of non-alcoholic fatty liver disease. Progress in Lipid Research, 52(1), 165-174.
Li, Y., Xu, S., Mihaylova, M. M., Zheng, B., Hou, X., Jiang, B., ... & Gao, B. (2011). AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metabolism, 13(4), 376-388.
Li, Z., Lan, D., Zhang, H., Zhang, H., Chen, X., & Sun, J. (2018). Electroacupuncture Mitigates Skeletal Muscular Lipid Metabolism Disorder Related to High-Fat-Diet Induced Insulin Resistance through the AMPK/ACC Signaling Pathway. Evidence-Based Complementary and Alternative Medicine, 2018.
Lionetti, L., Mollica, M. P., Lombardi, A., Cavaliere, G., Gifuni, G., & Barletta, A. (2009). From chronic overnutrition to insulin resistance: the role of fat-storing capacity and inflammation. Nutrition, Metabolism and Cardiovascular Diseases, 19(2), 146-152.
Lu, C. P., Huang, C. Y., Wang, S. H., Chiu, C. H., Li, L. H., Hua, K. F., & Wu, T. H. (2018). Improvement of hyperglycemia in a murine model of insulin resistance and high glucose-and inflammasome-mediated IL-1β expressions in macrophages by silymarin. Chemico-biological interactions, 290, 12-18
Maedler, K., Dharmadhikari, G., Schumann, D. M., & Størling, J. (2009). Interleukin-1 beta targeted therapy for type 2 diabetes. Expert Opinion on Biological Therapy, 9(9), 1177-1188.
Martinon, F., Burns, K., & Tschopp, J. (2002). The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. Molecular Cell, 10(2), 417-426.
Mazibuko-Mbeje, S. E., Dludla, P. V., Roux, C., Johnson, R., Ghoor, S., Joubert, E & Muller, C. J. (2019). Aspalathin-Enriched Green Rooibos Extract Reduces Hepatic Insulin Resistance by Modulating PI3K/AKT and AMPK Pathways. International journal of molecular sciences, 20(3), 633.
Michalopoulos, G. K., & DeFrances, M. C. (1997). Liver regeneration. Science, 276(5309), 60-66.
Moini, H., Tirosh, O., Park, Y. C., Cho, K. J., & Packer, L. (2002). R-α-lipoic acid action on cell redox status, the insulin receptor, and glucose uptake in 3T3-L1 adipocytes. Archives of biochemistry and biophysics, 397(2), 384-391.
Moore, J., Wright11, S. D., Hornung, V., & Latz, E. (2010). NLRP3 inflamasomes are required for atherogenesis and activated by cholesterol crystals that form early in disease. Nature, 464(7293), 1357-1361.
Nolan, C. J., Damm, P., & Prentki, M. (2011). Type 2 diabetes across generations: from pathophysiology to prevention and management. The Lancet, 378(9786), 169-181.
Odegaard, J. I., & Chawla, A. (2008). Mechanisms of macrophage activation in obesity-induced insulin resistance. Nature Reviews Endocrinology, 4(11), 619.
Orasanu, G., & Plutzky, J. (2009). The pathologic continuum of diabetic vascular disease. Journal of the American College of Cardiology, 53(5 Supplement), S35-S42.
Packer, L., Witt, E. H., & Tritschler, H. J. (1995). Alpha-lipoic acid as a biological antioxidant. Free Radical Biology and Medicine, 19(2), 227-250.
Perego, C., Da Dalt, L., Pirillo, A., Galli, A., Catapano, A. L., & Norata, G. D. (2019). Cholesterol metabolism, pancreatic β-cell function and diabetes. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease.
Pouysegur, J., Volmat, V., & Lenormand, P. (2002). Fidelity and spatio-temporal control in MAP kinase (ERKs) signalling. Biochemical pharmacology, 64(5-6), 755-763.
Rabøl, R., Petersen, K. F., Dufour, S., Flannery, C., & Shulman, G. I. (2011). Reversal of muscle insulin resistance with exercise reduces postprandial hepatic de novo lipogenesis in insulin resistant individuals. Proceedings of the National Academy of Sciences, 108(33), 13705-13709.

Rossetti, L., Smith, D., Shulman, G. I., Papachristou, D., & DeFronzo, R. A. (1987). Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats. The Journal of clinical investigation, 79(5), 1510-1515.
Ruderman, N. B., Carling, D., Prentki, M., & Cacicedo, J. M. (2013). AMPK, insulin resistance, and the metabolic syndrome. The Journal of Clinical Investigation, 123(7), 2764-2772.
Samuel, V. T., & Shulman, G. I. (2012). Mechanisms for insulin resistance: common threads and missing links. Cell, 148(5), 852-871.

Schneider, K. M., Mohs, A., Kilic, K., Candels, L. S., Elfers, C., Bennek, E., & Trautwein, C. (2019). Intestinal Microbiota Protects against MCD Diet-Induced Steatohepatitis. International journal of molecular sciences, 20(2), 308.
Schroder, K., Zhou, R., & Tschopp, J. (2010). The NLRP3 inflammasome: a sensor for metabolic danger? Science, 327(5963), 296-300.
Shao, B. Z., Xu, Z. Q., Han, B. Z., Su, D. F., & Liu, C. (2015). NLRP3 inflammasome and its inhibitors: a review. Frontiers in Pharmacology, 6, 262.
Shoelson, S. E., Lee, J., & Goldfine, A. B. (2006). Inflammation and insulin resistance. The Journal of Clinical Investigation, 116(7), 1793-1801.
Sola, S., Mir, M. Q., Cheema, F. A., Khan-Merchant, N., Menon, R. G., Parthasarathy, S., & Khan, B. V. (2005). Irbesartan and lipoic acid improve endothelial function and reduce markers of inflammation in the metabolic syndrome: results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (ISLAND) study. Circulation, 111(3), 343-348.
Sonnenberg, G. E., Hoffman, R. G., Mueller, R. A., & Kissebah, A. H. (1994). Splanchnic insulin dynamics and secretion pulsatilities in abdominal obesity. Diabetes, 43(3), 468-477.
Sozio, M. S., Lu, C., Zeng, Y., Liangpunsakul, S., & Crabb, D. W. (2011). Activated AMPK inhibits PPAR-α and PPAR-γ transcriptional activity in hepatoma cells. American Journal of Physiology-Gastrointestinal and Liver Physiology, 301(4), G739-G747.
Stephenson, K., Kennedy, L., Hargrove, L., Demieville, J., Thomson, J., Alpini, G., & Francis, H. (2018). Updates on Dietary Models of Nonalcoholic Fatty Liver Disease: Current Studies and Insights. Gene expression, 18(1), 5-17.
Stienstra, R., Joosten, L. A., Koenen, T., Van Tits, B., Van Diepen, J. A., Van Den Berg, S. A., & Kersten, S. (2010). The inflammasome-mediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity. Cell metabolism, 12(6), 593-605.
Takahashi, Y., Soejima, Y., & Fukusato, T. (2012). Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World journal of gastroenterology: WJG, 18(19), 2300.
Taniguchi, C. M., Emanuelli, B., & Kahn, C. R. (2006). Critical nodes in signalling pathways: insights into insulin action. Nature reviews Molecular cell biology, 7(2), 85
Tian, F., Zheng, Z., Zhang, D., He, S., & Shen, J. (2018). Efficacy of liraglutide in treating type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease. Bioscience Reports, BSR20181304.
Tseng, Y. H., Butte, A. J., Kokkotou, E., Yechoor, V. K., Taniguchi, C. M., Kriauciunas, K. M., & Kahn, C. R. (2005). Prediction of preadipocyte differentiation by gene expression reveals role of insulin receptor substrates and necdin. Nature cell biology, 7(6), 601.
Van Herck, M., Vonghia, L., & Francque, S. (2017). Animal models of nonalcoholic fatty liver disease—a starter’s guide. Nutrients, 9(10), 1072.
Vernon, G., Baranova, A., & Younossi, Z. M. (2011). Systematic review: the epidemiology and natural history of non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis in adults. Alimentary Pharmacology & Therapeutics, 34(3), 274-285.
Wang, Z., Hu, W., Lu, C., Ma, Z., Jiang, S., Gu, C. & Yang, Y. (2018). Targeting NLRP3 (Nucleotide-Binding Domain, Leucine-Rich–Containing Family, Pyrin Domain–Containing-3) Inflammasome in Cardiovascular Disorders. Arteriosclerosis, Thrombosis, and Vascular Biology, 38(12), 2765-2779.
Witters, L. A., & Kemp, B. E. (1992). Insulin activation of acetyl-CoA carboxylase accompanied by inhibition of the 5'-AMP-activated protein kinase. Journal of Biological Chemistry, 267(5), 2864-2867.
Ye, J. (2013). Mechanisms of insulin resistance in obesity. Frontiers of Medicine, 7(1), 14-24.
Yki J. H., Helve, E & Koivisto, V. A. (1987). Hyperglycemia decreases glucose uptake in type I diabetes. Diabetes, 36(8), 892-896
Zhang, M., Lv, X. Y., Li, J., Xu, Z. G., & Chen, L. (2009). The characterization of high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model. Experimental diabetes research, 2008.
Zhu, W., Feng, P. P., He, K., Li, S. W., & Gong, J. P. (2018). Liraglutide protects non-alcoholic fatty liver disease via inhibiting NLRP3 inflammasome activation in a mouse model induced by high-fat diet. Biochemical and Biophysical Research Communications, 505(2), 523-529.
Zraika, S., Hull, R. L., Verchere, C. B., Clark, A., Potter, K. J., Fraser, P. E., & Kahn, S. E. (2010). Toxic oligomers and islet beta cell death: guilty by association or convicted by circumstantial evidence?. Diabetologia, 53(6), 1046-1056.