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肥胖2型糖尿病药物研究进展

张宇 王鹏源 刘霞

张宇, 王鹏源, 刘霞. 肥胖2型糖尿病药物研究进展[J]. 药学实践与服务, 2019, 37(2): 97-102. doi: 10.3969/j.issn.1006-0111.2019.02.001
引用本文: 张宇, 王鹏源, 刘霞. 肥胖2型糖尿病药物研究进展[J]. 药学实践与服务, 2019, 37(2): 97-102. doi: 10.3969/j.issn.1006-0111.2019.02.001
ZHANG Yu, WANG Pengyuan, LIU Xia. Research progress on obesity type 2 diabetes mellitus drug[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(2): 97-102. doi: 10.3969/j.issn.1006-0111.2019.02.001
Citation: ZHANG Yu, WANG Pengyuan, LIU Xia. Research progress on obesity type 2 diabetes mellitus drug[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(2): 97-102. doi: 10.3969/j.issn.1006-0111.2019.02.001

肥胖2型糖尿病药物研究进展

doi: 10.3969/j.issn.1006-0111.2019.02.001
基金项目: 重大新药创制科技重大专项(2018ZX09711002-003-015),上海市"科技创新行动计划"生物医药领域科技支撑项目(18431900800);国家自然科学基金(81473259,81773726)

Research progress on obesity type 2 diabetes mellitus drug

  • 摘要: 肥胖与糖尿病发病率密切相关,是糖尿病发病率上升的重要原因。如今上市的大部分降糖药物如胰岛素及其类似物、胰岛素促泌剂、胰岛素增敏剂等都会不同程度的增加患者体重,从而加重胰岛素抵抗,增加降糖药物剂量,形成恶性循环,降糖兼具减肥是当今糖尿病新药研发重要趋势。本文概述了肥胖2型糖尿病的流行病学以及目前上市的降糖药物对体重发展的影响,并重点概述了兼具减肥效应的降糖药物的最新靶点,为肥胖2型糖尿病患者的治疗提供潜在新方法。
  • [1] YANGS H,DOU K F,SONG W J. Prevalence of diabetes among men and women in China[J]. N Engl J Med,2010,362(25):2425-2426.
    [2] MENKE A,RUSTK F,FRADKIN J,et al. Associations between trends in race/ethnicity,aging,and body mass index with diabetes prevalence in the United States:A series of cross-sectional studies[J]. Ann Intern Med,2014,161(5):328-335.
    [3] TABATA S,YOSHIMITSU S,HAMACHI T,et al. Waist circumference and insulin resistance:A cross-sectional study of Japanese men[J]. BMC Endocr Disord,2009,9:1.
    [4] DIABETES PREVENTION PROGRAM RESEARCH GROUP. Relationship of body size and shape to the development of diabetes in the diabetes prevention program[J]. Obesity (Silver Spring),2006,14(11):2107-2117.
    [5] LAKE S,KROOK A,ZIERATHJ R. Analysis of insulin signaling pathways through comparative genomics. Mapping mechanisms for insulin resistance in type 2(non-insulin-dependent) diabetes mellitus[J]. Exp Clin Endocrinol Diabetes,2003,111(4):191-197.
    [6] 项坤三,贾伟平,陆俊茜. 中国上海地区40岁以上成人中肥胖与代谢综合征的关系[J]. 中华内科杂志,2000,39(4):224.
    [7] LASTRA G,MANRIQUE C,SOWERSJ R. Obesity,cardiometabolic syndrome,and chronic kidney disease:the weight of the evidence[J]. Adv Chronic Kidney Dis,2006,13(4):365-373.
    [8] NAVANEETHANS D,YEHNERT H,MOUSTARAH F,et al. Weight loss interventions in chronic kidney disease:A systematic review and meta-analysis[J]. Clin J Am Soc Nephrol,2009,4(10):1565-1574.
    [9] 徐斯盛,张惠斌,周金培,等. 新型抗糖尿病药物的研究进展[J].中国药科大学学报,2011,42(2):97-106.
    [10] 中华医学会糖尿病学分会.中国2型糖尿病防治指南(2013年版)[J].中华内分泌代谢杂志,2014,30(10):893-942.
    [11] BARNETTA H. Complementing insulin therapy to achieve glycemic control[J]. Adv Ther,2013,30(6):557-576.
    [12] MONAMI M,DICEMBRINI I,KUNDISOVA L,et al. A meta-analysis of the hypoglycaemic risk in randomized controlled trials with sulphonylureas in patients with type 2 diabetes[J]. Diabetes Obes Metab,2014,16(9):833-840.
    [13] FUHLENDORFF J,RORSMAN P,KOFOD H,et al. Stimulation of insulin release by repaglinide and glibenclamide involves both common and distinct processes[J]. Diabetes,1998,47(3):345-351.
    [14] BLACK C,DONNELLY P,MCINTYRE L,et al. Meglitinide analogues for type 2 diabetes mellitus[J]. Cochrane Database Syst Rev,2007(2):CD004654.
    [15] DOMECQJ P,PRUTSKY G,LEPPIN A,et al. Clinical review:Drugs commonly associated with weight change:A systematic review and meta-analysis[J]. J Clin Endocrinol Metab,2015,100(2):363-370.
    [16] NAUCKM A,MEIER J J. The incretin effect in healthy individuals and those with type 2 diabetes:physiology,pathophysiology,and response to therapeutic interventions[J]. Lancet Diabetes Endocrinol,2016,4(6):525-536.
    [17] GARBER A,HENRY R,RATNER R,et al. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono):A randomised,52-week,phase Ⅲ,double-blind,parallel-treatment trial[J]. Lancet,2009,373(9662):473-481.
    [18] WILDINGJ P. The role of the kidneys in glucose homeostasis in type 2 diabetes:clinical implications and therapeutic significance through sodium glucose co-transporter 2 inhibitors[J]. Metab Clin Exp,2014,63(10):1228-1237.
    [19] ROSENSTOCK J,JELASKA A,WANG F,et al. Empagliflozin as add on tobasal insulin for 78 weeks improves glycemic control with weightloss in insulin-treated type 2 diabetes (T2DM)[J]. Can J Diabetes,2013;37:S32.
    [20] HOLMBOE E S. Oral antihyperglycemic therapy for type 2 diabetes:clinical applications[J]. JAMA,2002,287(3):373-376.
    [21] GARBER A J,ABRAHAMSON M J,BARZILAY J I,et al. AACE/ACE comprehensive diabetes management algorithm 2015[J]. Endocr Pract,2015,21(4):438-447.
    [22] MORI Y,MAMORI S,TAJIMA N. Weight loss-associated changes in acute effects of nateglinide on insulin secretion after glucose loading:results of glucose loading on 2 consecutive days[J]. Diabetes Obes Metab,2005,7(2):182-188.
    [23] SUBAUSTE A,BURANT C F. DGAT:Novel therapeutic target for obesity and type 2 diabetes mellitus[J]. Curr Drug Targets Immune Endocr Metabol Disord,2003,3(4):263-270.
    [24] RAMACHANDRAN C,KENNEDY B P. Protein tyrosine phosphatase 1B:a novel target for type 2 diabetes and obesity[J]. Curr Top Med Chem,2003,3(7):749-757.
    [25] WADA T,SASAOKA T,FUNAKI M,et al. Over expression of SH2-containing inositol phosphatase 2 results in negative regulation of insulin-induced metabolic actions in 3T3-L1 adipocytes via its 5'-phosphatase catalytic activity[J]. Mol Cell Biol 2001,21(5):1633-1646.
    [26] SASAOKA T,WADA T,TSUNEKI H. Lipid phosphatases as a possible therapeutic target in cases of type 2 diabetes and obesity[J]. Pharmacol Ther,2006,112(3):799-809.
    [27] FLATT P R. Gastric inhibitory polypeptide (GIP) revisited:a new therapeutic target for obesity-diabetes[J]. Diabet Med,2008,25(7):759-764.
    [28] ABDEL-MAGID A F.GPR119 Modulators for the Treatment of Diabetes,Obesity,and Related Diseases:Patent Highlight[J]. ACS Med Chem Lett,2012,3(12):955-958.
    [29] OVERTON H A,FYFE M C,REYNET C. GPR119,a novel G protein-coupled receptor target for the treatment of type 2 diabetes and obesity[J]. Br J Pharmacol,2008,153(Suppl 1):S76-S81.
    [30] LAMBERT D M,MUCCIOLI G G. Endocannabinoids and related N-acylethanolamines in the control of appetite and energy metabolism:emergence of new molecular players[J]. Curr Opin Clin Nutr Metab Care,2007,10(6):735-744.
    [31] PATTI M E. Rehashing endocannabinoid antagonists:can we selectively target the periphery to safely treat obesity and type 2 diabetes?[J]. J Clin Invest,2010,120(8):2646-2648.
    [32] BOSTRÖM P,WU J,JEDRYCHOWSKI M P,et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis[J]. Nature,2012,481(7382):463-468.
    [33] YEN C L,STONE S J,CASES S,et al. Identification of a gene encoding MGAT1,a monoacylglycerol acyltransferase[J]. Proc Natl Acad Sci USA,2002,99(13):8512-8517.
    [34] HAYASHI Y,SUEMITSU E,KAJIMOTO K,et al. Hepatic monoacylglycerol O-acyltransferase 1 as a promising therapeutic target for steatosis,obesity,and type 2 diabetes[J]. Mol Ther Nucleic Acids,2014,3:e154.
    [35] FUJIMOTO T,KOYANAGI M,BABA I,et al. Analysis of KRAP expression and localization,and genes regulated by KRAP in a human colon cancer cell line[J]. J Hum Genet,2007,52(12):978-984.
    [36] FUJIMOTO T,MIYASAKA K,KOYANAGI M,et al. Altered energy homeostasis and resistance to diet-induced obesity in KRAP-deficient mice[J]. PLoS ONE,2009,4(1):e4240.
    [37] GONZÁLEZ N,MORENO P,JENSEN R T. Bombesin receptor subtype 3 as a potential target for obesity and diabetes[J]. Expert Opin Ther Targets,2015,19(9):1153-1170.
    [38] DE PERGOLA G,MANICONE M,LOVERO R,et al. Influence of a family history of type Ⅱ diabetes on fasting leptin and adiponectin plasma levels[J]. Med J Nutrition Metab,2008,1(2):121-127.
    [39] ACHARI A E,JAIN S K. Adiponectin,a therapeutic target for obesity,diabetes,and endothelial dysfunction[J]. Int J Mol Sci. 2017,18(6),1321.
    [40] HANSEN J S,CLEMMESEN J O,SECHER N H,et al. Glucagon-to-insulin ratio is pivotal for splanchnic regulation of FGF-21 in humans[J]. Mol Metab,2015,4(8):551-560.
    [41] KRUSE R,VIENBERG S G,VIND B F,et al. Effects of insulin and exercise training on FGF21,its receptors and target genes in obesity and type 2 diabetes[J]. Diabetologia,2017,60(10):2042-2051.
    [42] ELFERS C T,ROTH C L. Robust reductions of excess weight and hyperphagia by beloranib in rat models of genetic and hypothalamic obesity[J]. Endocrinology,2017,158(1):41-55.
    [43] BURKEY B F,HOGLEN N C,INSKEEP P,et al. Preclinical efficacy and safety of the novel antidiabetic,antiobesity MetAP2 inhibitor ZGN-1061[J]. J Pharmacol Exp Ther,2018,365(2):301-313.
    [44] ANLAUF M,WEIHE E,HARTSCHUH W,et al. Localization of xenin-immunoreactive cells in the duodenal mucosa of humans and various mammals[J]. J Histochem Cytochem,2000,48(12):1617-1626.
    [45] HASIB A,NG M T,GAULT V A,et al. An enzymatically stable GIP/xenin hybrid peptide restores GIP sensitivity,enhances beta cell function and improves glucose homeostasis in high-fat-fed mice[J]. Diabetologia,2017,60(3):541-552.
    [46] 邹大进,张征. 肥胖与2型糖尿病的治疗新靶点:脂肪细胞型脂肪酸结合蛋白的抑制研究方兴未艾[J]. 中华糖尿病杂志,2016,8(2):65-67.
    [47] ALFADDA A A,FATMA S,CHISHTI M A,et al. Orosomucoid serum concentrations and fat depot-specific mRNA and protein expression in humans[J]. Mol Cells,2012,33(1):35-41.
    [48] SUN Y,YANG Y,QIN Z,et al. The acute-phase protein orosomucoid regulates food intake and energy homeostasis via leptin receptor signaling pathway[J]. Diabetes,2016,65(6):1630-1641.
    [49] SUN Y,YANG Y L,QIN Z,et al. The acute-phase protein orosomucoid regulates food intake and energy homeostasis via leptin receptor signaling pathway[J]. Diabetes,2016,65(6):1630-1641.[PubMed]
    [50] PATHAK P,LIU H L,BOEHME S,et al. Farnesoid X receptor induces Takeda G-protein receptor 5 cross-talk to regulate bile acid synthesis and hepatic metabolism[J]. J Biol Chem,2017,292(26):11055-11069.
    [51] CHÁVEZ-TALAVERA O,TAILLEUX A,LEFEBVRE P,et al. Bile acid control of metabolism and inflammation in obesity,type 2 diabetes,dyslipidemia,and nonalcoholic fatty liver disease[J]. Gastroenterology,2017,152(7):1679-1694.
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肥胖2型糖尿病药物研究进展

doi: 10.3969/j.issn.1006-0111.2019.02.001
    基金项目:  重大新药创制科技重大专项(2018ZX09711002-003-015),上海市"科技创新行动计划"生物医药领域科技支撑项目(18431900800);国家自然科学基金(81473259,81773726)

摘要: 肥胖与糖尿病发病率密切相关,是糖尿病发病率上升的重要原因。如今上市的大部分降糖药物如胰岛素及其类似物、胰岛素促泌剂、胰岛素增敏剂等都会不同程度的增加患者体重,从而加重胰岛素抵抗,增加降糖药物剂量,形成恶性循环,降糖兼具减肥是当今糖尿病新药研发重要趋势。本文概述了肥胖2型糖尿病的流行病学以及目前上市的降糖药物对体重发展的影响,并重点概述了兼具减肥效应的降糖药物的最新靶点,为肥胖2型糖尿病患者的治疗提供潜在新方法。

English Abstract

张宇, 王鹏源, 刘霞. 肥胖2型糖尿病药物研究进展[J]. 药学实践与服务, 2019, 37(2): 97-102. doi: 10.3969/j.issn.1006-0111.2019.02.001
引用本文: 张宇, 王鹏源, 刘霞. 肥胖2型糖尿病药物研究进展[J]. 药学实践与服务, 2019, 37(2): 97-102. doi: 10.3969/j.issn.1006-0111.2019.02.001
ZHANG Yu, WANG Pengyuan, LIU Xia. Research progress on obesity type 2 diabetes mellitus drug[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(2): 97-102. doi: 10.3969/j.issn.1006-0111.2019.02.001
Citation: ZHANG Yu, WANG Pengyuan, LIU Xia. Research progress on obesity type 2 diabetes mellitus drug[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(2): 97-102. doi: 10.3969/j.issn.1006-0111.2019.02.001
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