ANGPTL8/Betatrophin Improves Glucose Tolerance in Older Mice and Metabolomic Analysis Reveals Its Role in Insulin Resistance in HepG2 Cells

References

• Guo S . Insulin signaling, resistance, and the metabolic syndrome: insights from mouse models into disease mechanisms. J Endocrinol . 2014;220:T1–T23. doi:10.1530/JOE-13-0584 24281010
   PubMed Web of Science ®Google Scholar
• Guzman-Flores JM , Flores-Perez EC , Hernandez-Ortiz M , et al. Protein expression profile of twenty-week-old diabetic db/db and non-diabetic mice livers: a proteomic and bioinformatic analysis. Biomolecules . 2018;8:35.
   Web of Science ®Google Scholar
• Loh M , Zhou L , Ng HK , Chambers JC . Epigenetic disturbances in obesity and diabetes: epidemiological and functional insights. Mol Metab . 2019;27S:S33–S41.31500829
   PubMed Web of Science ®Google Scholar
• Abu-Farha M , Abubaker J , Tuomilehto J . ANGPTL8 (betatrophin) role in diabetes and metabolic diseases. Diabetes Metab Res Rev . 2017;33:e2919.
   Web of Science ®Google Scholar
• Zhang Y , Li R , Meng Y , et al. Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling. Diabetes . 2014;63:514–525. doi:10.2337/db13-1106 24150604
   PubMed Web of Science ®Google Scholar
• Endo M . The roles of ANGPTL families in cancer progression. J UOEH . 2019;41:317–325. doi:10.7888/juoeh.41.317 31548486
   PubMedGoogle Scholar
• Zhang Y , Li S , Donelan W , et al. Angiopoietin-like protein 8 (betatrophin) is a stress-response protein that down-regulates expression of adipocyte triglyceride lipase. Biochim Biophys Acta . 2016;1861:130–137. doi:10.1016/j.bbalip.2015.11.003 26569053
   PubMed Web of Science ®Google Scholar
• Santulli G . Angiopoietin-like proteins: a comprehensive look. Front Endocrinol (Lausanne) . 2014;5:4. doi:10.3389/fendo.2014.00004 24478758
   PubMed Web of Science ®Google Scholar
• Calle MC , Fernandez ML . Inflammation and type 2 diabetes. Diabetes Metab . 2012;38:183–191. doi:10.1016/j.diabet.2011.11.006 22252015
   PubMed Web of Science ®Google Scholar
• Hu FB , Meigs JB , Li TY , Rifai N , Manson JE . Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes . 2004;53:693–700. doi:10.2337/diabetes.53.3.693 14988254
   PubMed Web of Science ®Google Scholar
• Fornoni A , Ijaz A , Tejada T , Lenz O . Role of inflammation in diabetic nephropathy. Curr Diabetes Rev . 2008;4:10–17. doi:10.2174/157339908783502361 18220690
   PubMedGoogle Scholar
• Abbatecola AM , Ferrucci L , Grella R , et al. Diverse effect of inflammatory markers on insulin resistance and insulin-resistance syndrome in the elderly. J Am Geriatr Soc . 2004;52:399–404. doi:10.1111/j.1532-5415.2004.52112.x 14962155
   PubMed Web of Science ®Google Scholar
• Escobar-Morreale HF , Villuendas G , Botella-Carretero JI , Sancho J , San MJ . Obesity, and not insulin resistance, is the major determinant of serum inflammatory cardiovascular risk markers in pre-menopausal women. Diabetologia . 2003;46:625–633. doi:10.1007/s00125-003-1090-z 12739017
   PubMed Web of Science ®Google Scholar
• Martins CC , Bagatini MD , Simoes J , et al. Increased oxidative stress and inflammatory markers contrasting with the activation of the cholinergic anti-inflammatory pathway in patients with metabolic syndrome. Clin Biochem . 2021;89:63–69. doi:10.1016/j.clinbiochem.2020.12.007 33333061
   PubMed Web of Science ®Google Scholar
• Black HR , Davis B , Barzilay J , et al. Metabolic and clinical outcomes in nondiabetic individuals with the metabolic syndrome assigned to chlorthalidone, amlodipine, or lisinopril as initial treatment for hypertension: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Diabetes Care . 2008;31:353–360.18000186
   PubMed Web of Science ®Google Scholar
• Abbatecola AM , Olivieri F , Corsonello A , et al. Frailty and safety: the example of diabetes. Drug Saf . 2012;35(Suppl 1):63–71. doi:10.1007/BF03319104 23446787
   PubMed Web of Science ®Google Scholar
• Hu H , Sun W , Yu S , et al. Increased circulating levels of betatrophin in newly diagnosed type 2 diabetic patients. Diabetes Care . 2014;37:2718–2722. doi:10.2337/dc14-0602 25024395
   PubMed Web of Science ®Google Scholar
• Chen X , Lu P , He W , et al. Circulating betatrophin levels are increased in patients with type 2 diabetes and associated with insulin resistance. J Clin Endocrinol Metab . 2015;100:E96–E100. doi:10.1210/jc.2014-2300 25303484
   PubMed Web of Science ®Google Scholar
• Lu P , Chen X , Zhang Z , et al. Insulin upregulates betatrophin expression via PI3K/Akt pathway. Sci Rep . 2017;7:5594. doi:10.1038/s41598-017-06052-y 28717133
   PubMed Web of Science ®Google Scholar
• Yi P , Park JS , Melton DA . Betatrophin: a hormone that controls pancreatic beta cell proliferation. Cell . 2013;153:747–758. doi:10.1016/j.cell.2013.04.008 23623304
   PubMed Web of Science ®Google Scholar
• Abu-Farha M , Ghosh A , Al-Khairi I , et al. The multi-faces of Angptl8 in health and disease: novel functions beyond lipoprotein lipase modulation. Prog Lipid Res . 2020;80:101067. doi:10.1016/j.plipres.2020.101067 33011191
   PubMed Web of Science ®Google Scholar
• Zhang Y , Guo X , Yan W , et al. ANGPTL8 negatively regulates NF-kappaB activation by facilitating selective autophagic degradation of IKKgamma. Nat Commun . 2017;8:2164. doi:10.1038/s41467-017-02355-w 29255244
   PubMed Web of Science ®Google Scholar
• Yang J , Song QY , Niu SX , et al. Emerging roles of angiopoietin-like proteins in inflammation: mechanisms and potential as pharmacological targets. J Cell Physiol . 2021. doi:10.1002/jcp.30534
   Web of Science ®Google Scholar
• Gusarova V , Alexa CA , Na E , et al. ANGPTL8/betatrophin does not control pancreatic beta cell expansion. Cell . 2014;159:691–696. doi:10.1016/j.cell.2014.09.027 25417115
   PubMed Web of Science ®Google Scholar
• Cox AR , Lam CJ , Bonnyman CW , et al. Angiopoietin-like protein 8 (ANGPTL8)/betatrophin overexpression does not increase beta cell proliferation in mice. Diabetologia . 2015;58:1523–1531. doi:10.1007/s00125-015-3590-z 25917759
   PubMed Web of Science ®Google Scholar
• Rong GX , Li WX , Chen Y , et al. ANGPTL8/betatrophin alleviates insulin resistance via the Akt-GSK3beta or Akt-FoxO1 pathway in HepG2 cells. Exp Cell Res . 2016;345:158–167. doi:10.1016/j.yexcr.2015.09.012 26387753
   PubMed Web of Science ®Google Scholar
• Zhang Z , Wu H , Dai L , et al. ANGPTL8 enhances insulin sensitivity by directly activating insulin-mediated AKT phosphorylation. Gene . 2020;749:144707. doi:10.1016/j.gene.2020.144707 32344005
   PubMed Web of Science ®Google Scholar
• Xu F , Chen Y , Wang N , Sun K . Bacteria-derived recombinant human ANGPTL8/Betatrophin significantly increases the level of triglyceride. Protein J . 2019;38:472–478. doi:10.1007/s10930-019-09825-8 30929133
   PubMed Web of Science ®Google Scholar
• Concordet JP , Haeussler M . CRISPOR: intuitive guide selection for CRISPR/Cas9 genome editing experiments and screens. Nucleic Acids Res . 2018;46:W242–W245. doi:10.1093/nar/gky354 29762716
   PubMed Web of Science ®Google Scholar
• Wang Y , Quagliarini F , Gusarova V , et al. Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis. Proc Natl Acad Sci U S A . 2013;110:16109–16114. doi:10.1073/pnas.1315292110 24043787
   PubMed Web of Science ®Google Scholar
• Saeedi P , Petersohn I , Salpea P , et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Res Clin Pract . 2019;157:107843. doi:10.1016/j.diabres.2019.107843 31518657
   PubMed Web of Science ®Google Scholar
• Aguayo-Mazzucato C , Bonner-Weir S . Pancreatic beta cell regeneration as a possible therapy for diabetes. Cell Metab . 2018;27:57–67. doi:10.1016/j.cmet.2017.08.007 28889951
   PubMed Web of Science ®Google Scholar
• Kadowaki T , Yamauchi T , Kubota N , et al. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest . 2006;116:1784–1792. doi:10.1172/JCI29126 16823476
   PubMed Web of Science ®Google Scholar
• Esteghamati A , Alamdari A , Zandieh A , et al. Serum visfatin is associated with type 2 diabetes mellitus independent of insulin resistance and obesity. Diabetes Res Clin Pract . 2011;91:154–158. doi:10.1016/j.diabres.2010.11.003 21122936
   PubMed Web of Science ®Google Scholar
• Gouranton E , Romier B , Marcotorchino J , et al. Visfatin is involved in TNFalpha-mediated insulin resistance via an NAD(+)/Sirt1/PTP1B pathway in 3T3-L1 adipocytes. Adipocyte . 2014;3:180–189. doi:10.4161/adip.28729 25068084
   PubMedGoogle Scholar
• Aktas G , Alcelik A , Ozlu T , et al. Association between omentin levels and insulin resistance in pregnancy. Exp Clin Endocrinol Diabetes . 2014;122:163–166. doi:10.1055/s-0034-1370917 24643693
   PubMed Web of Science ®Google Scholar
• Nway NC , Sitticharoon C , Chatree S , Maikaew P . Correlations between the expression of the insulin sensitizing hormones, adiponectin, visfatin, and omentin, and the appetite regulatory hormone, neuropeptide Y and its receptors in subcutaneous and visceral adipose tissues. Obes Res Clin Pract . 2016;10:256–263. doi:10.1016/j.orcp.2015.05.007 26067914
   PubMed Web of Science ®Google Scholar
• Lee S , Zhang C , Kilicarslan M , et al. Integrated network analysis reveals an association between plasma mannose levels and insulin resistance. Cell Metab . 2016;24:172–184. doi:10.1016/j.cmet.2016.05.026 27345421
   PubMed Web of Science ®Google Scholar
• Amano E , Funakoshi S , Yoshimura K , et al. Fasting plasma mannose levels are associated with insulin sensitivity independent of BMI in Japanese individuals with diabetes. Diabetol Metab Syndr . 2018;10:88. doi:10.1186/s13098-018-0391-9 30534205
   PubMed Web of Science ®Google Scholar
• Holmes D . Biomarkers: mannose levels predict insulin resistance. Nat Rev Endocrinol . 2016;12:496. doi:10.1038/nrendo.2016.119
   Google Scholar
• Ferrannini E , Bokarewa M , Brembeck P , et al. Mannose is an insulin-regulated metabolite reflecting whole-body insulin sensitivity in man. Metabolism . 2020;102:153974. doi:10.1016/j.metabol.2019.153974 31682799
   PubMed Web of Science ®Google Scholar
• Beltramo E , Berrone E , Tarallo S , Porta M . Effects of thiamine and benfotiamine on intracellular glucose metabolism and relevance in the prevention of diabetic complications. Acta Diabetol . 2008;45:131–141. doi:10.1007/s00592-008-0042-y 18581039
   PubMed Web of Science ®Google Scholar
• Alaei SF , Soares MJ , Zhao Y , Sherriff J . High-dose thiamine supplementation improves glucose tolerance in hyperglycemic individuals: a randomized, double-blind cross-over trial. Eur J Nutr . 2013;52:1821–1824. doi:10.1007/s00394-013-0534-6 23715873
   PubMed Web of Science ®Google Scholar
• Karkabounas S , Papadopoulos N , Anastasiadou C , et al. Effects of alpha-lipoic acid, carnosine, and thiamine supplementation in obese patients with Type 2 diabetes mellitus: a randomized, double-blind study. J Med Food . 2018;21:1197–1203. doi:10.1089/jmf.2018.0007 30311825
   PubMed Web of Science ®Google Scholar
• Zhao H , Li Z , Tian G , et al. Effects of traditional Chinese medicine on rats with Type II diabetes induced by high-fat diet and streptozotocin: a urine metabonomic study. Afr Health Sci . 2013;13:673–681.24250306
   PubMed Web of Science ®Google Scholar
• Kurek K , Garbowska M , Ziembicka DM , et al. Myriocin treatment affects lipid metabolism in skeletal muscles of rats with streptozotocin-induced type 1 diabetes. Adv Med Sci . 2017;62:65–73. doi:10.1016/j.advms.2016.04.003 28189121
   PubMed Web of Science ®Google Scholar
• Zywno H , Bzdega W , Kolakowski A , et al. The influence of coumestrol on sphingolipid signaling pathway and insulin resistance development in primary rat hepatocytes. Biomolecules . 2021;11:268.33673122
   PubMed Web of Science ®Google Scholar
• Wang H , Brown PC , Chow E , et al. 3D cell culture models: drug pharmacokinetics, safety assessment, and regulatory consideration. Clin Transl Sci . 2021. doi:10.1111/cts.13066
   Web of Science ®Google Scholar