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肥胖2型糖尿病药物研究进展

张宇,  王鹏源,  刘霞

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文章导航 > 药学实践与服务  > 2019 >  37(2): 97-102
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
shu
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
shu

肥胖2型糖尿病药物研究进展

doi: 10.3969/j.issn.1006-0111.2019.02.001

  • 海军军医大学药学院药理学教研室, 上海 200433

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

  • Department of Pharmacology, School of Pharmacy, Naval Medical University, Shanghai 200433, China

  • 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。
    Abstract: Obesity is closely relative to the increase in diabetes incidence. Most of the current hypoglycemic medicines,such as insulin and its analogues,insulin secretion enhancers,insulin sensitizers and so on,would lead to weight gain,thus aggravating insulin resistance and increasing the dosage of hypoglycemic drugs,which had formed a vicious circle. The development of new drugs targeting both reducing blood sugar and controlling weight had attracted much more attention. the epidemiology of obese type 2 diabetes mellitus and the effect of currently available hypoglycemic drugs on weight development had been reviewed in this article,and the latest targets of hypoglycemic medicines with weight loss effects were highlighted,in order to provide a potential approach for the treatment of obese type 2 diabetes mellitus.
  • [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
  • 海军军医大学药学院药理学教研室, 上海 200433
    • 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）
  • 收稿日期: 2018-09-05
  • 修回日期: 2019-01-03

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
shu
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
shu

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