Abstract
Background: Recent studies have suggested that hyperglycaemia influences the bile acid profile and concentrations of secondary bile acids in the gut.
Introduction: This study aimed to measure changes in the bile acid profile in the gut, tissues, and faeces in type 1 Diabetes (T1D) and Type 2 Diabetes (T2D). Methods: T1D and T2D were established in a mouse model. Twenty-one seven-weeks old balb/c mice were randomly divided into three equal groups, healthy, T1D and T2D. Blood, tissue, urine and faeces samples were collected for bile acid measurements. Results: Compared with healthy mice, T1D and T2D mice showed lower levels of the primary bile acid, chenodeoxycholic acid, in the plasma, intestine, and brain, and higher levels of the secondary bile acid, lithocholic acid, in the plasma and pancreas. Levels of the bile acid ursodeoxycholic acid were undetected in healthy mice but were found to be elevated in T1D and T2D mice. Conclusion: Bile acid profiles in other organs were variably influenced by T1D and T2D development, which suggests similarity in effects of T1D and T2D on the bile acid profile, but these effects were not always consistent among all organs, possibly since feedback mechanisms controlling enterohepatic recirculation and bile acid profiles and biotransformation are different in T1D and T2D.Keywords: Type 1 diabetes, type 2 diabetes, lithocholic acid, secondary bile acids, chenodeoxycholic acid, balb/c mice.
[1]
Mikov M, Fawcett JP, Kuhajda K, Kevresan S. Pharmacology of bile acids and their derivatives: absorption promoters and therapeutic agents. Eur J Drug Metab Pharmacokinet 2006; 31(3): 237-51.
[http://dx.doi.org/10.1007/BF03190714] [PMID: 17136862]
[http://dx.doi.org/10.1007/BF03190714] [PMID: 17136862]
[2]
Kuhajda K, Kandrac J, Kevresan S, Mikov M, Fawcett JP. Structure and origin of bile acids: an overview. Eur J Drug Metab Pharmacokinet 2006; 31(3): 135-43.
[http://dx.doi.org/10.1007/BF03190710] [PMID: 17136858]
[http://dx.doi.org/10.1007/BF03190710] [PMID: 17136858]
[3]
Mikov M, Al-Salami H, Golocorbin-Kon S, Skrbic R, Raskovic A, Fawcett JP. The influence of 3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate on gliclazide pharmacokinetics and glucose levels in a rat model of diabetes. Eur J Drug Metab Pharmacokinet 2008; 33(3): 137-42.
[http://dx.doi.org/10.1007/BF03191110] [PMID: 19007038]
[http://dx.doi.org/10.1007/BF03191110] [PMID: 19007038]
[4]
Mikov MA-SH, Golocorbin-Kon G. Potentials and Limitations of Bile Acids and Probiotics in Diabetes Mellitus. 2012; pp. 365-402.
[5]
Negrulj R, Mooranian A, Al-Salami H. Potentials and Limitations of Bile Acids in Type 2 Diabetes Mellitus: Applications of Microencapsulation as a Novel Oral Delivery System. J Endocrinol Diabetes Mellit 2013; 1(2): 49-59.
[6]
Mooranian A, Negrulj R, Mathavan S, et al. Stability and Release Kinetics of an Advanced Gliclazide-Cholic Acid Formulation: The Use of Artificial-Cell Microencapsulation in Slow Release Targeted Oral Delivery of Antidiabetics. J Pharm Innov 2014; 9(2): 150-7.
[http://dx.doi.org/10.1007/s12247-014-9182-5] [PMID: 24829616]
[http://dx.doi.org/10.1007/s12247-014-9182-5] [PMID: 24829616]
[7]
Mooranian A, Negrulj R, Al-Sallami HS, et al. Probucol release from novel multicompartmental microcapsules for the oral targeted delivery in type 2 diabetes. AAPS PharmSciTech 2015; 16(1): 45-52.
[http://dx.doi.org/10.1208/s12249-014-0205-9] [PMID: 25168450]
[http://dx.doi.org/10.1208/s12249-014-0205-9] [PMID: 25168450]
[8]
Mooranian A, Negrulj R, Mathavan S, et al. An advanced microencapsulated system: a platform for optimized oral delivery of antidiabetic drug-bile acid formulations. Pharm Dev Technol 2015; 20(6): 702-9.
[http://dx.doi.org/10.3109/10837450.2014.915570] [PMID: 24798888]
[http://dx.doi.org/10.3109/10837450.2014.915570] [PMID: 24798888]
[9]
Mooranian A, Negrulj R, Al-Salami H. Primary bile acid chenodeoxycholic acid-based microcapsules to examine beta-cell survival and the inflammatory response. Bionanoscience 2016; 6(2): 103-9.
[http://dx.doi.org/10.1007/s12668-016-0198-9]
[http://dx.doi.org/10.1007/s12668-016-0198-9]
[10]
Mooranian A, Negrulj R, Al-Salami H. The impact of allylamine-bile acid combinations on cell delivery microcapsules in diabetes. J Microencapsul 2016; 33(6): 569-74.
[http://dx.doi.org/10.1080/02652048.2016.1228703] [PMID: 27574968]
[http://dx.doi.org/10.1080/02652048.2016.1228703] [PMID: 27574968]
[11]
Mooranian A, Zamani N, Takechi R, et al. Pharmacological effects of nanoencapsulation of human-based dosing of probucol on ratio of secondary to primary bile acids in gut, during induction and progression of type 1 diabetes. Artif Cells Nanomed Biotechnol 2018.46(sup3): S748-54..
[http://dx.doi.org/10.1080/21691401.2018.1511572] [PMID: 30422681]
[http://dx.doi.org/10.1080/21691401.2018.1511572] [PMID: 30422681]
[12]
Mooranian A, Zamani N, Mikov M, et al. Eudragit®-based microcapsules of probucol with a gut-bacterial processed secondary bile acid. Ther Deliv 2018; 9(11): 811-21.
[http://dx.doi.org/10.4155/tde-2018-0036] [PMID: 30444461]
[http://dx.doi.org/10.4155/tde-2018-0036] [PMID: 30444461]
[13]
Mooranian A, Zamani N, Mikov M, et al. Novel nano-encapsulation of probucol in microgels: scanning electron micrograph characterizations, buoyancy profiling, and antioxidant assay analyses. Artif Cells Nanomed Biotechnol 2018.46(sup3): S741-7..
[http://dx.doi.org/10.1080/21691401.2018.1511571] [PMID: 30260253]
[http://dx.doi.org/10.1080/21691401.2018.1511571] [PMID: 30260253]
[14]
Mooranian A, Takechi R, Jamieson E, Morahan G, Al-Salami H. The effect of molecular weights of microencapsulating polymers on viability of mouse-cloned pancreatic β-cells: biomaterials, osmotic forces and potential applications in diabetes treatment. Pharm Dev Technol 2018; 23(2): 145-50.
[http://dx.doi.org/10.1080/10837450.2017.1321664] [PMID: 28425308]
[http://dx.doi.org/10.1080/10837450.2017.1321664] [PMID: 28425308]
[15]
Mooranian A, Negrulj R, Takechi R, Mamo J, Al-Sallami H, Al-Salami H. The biological effects of the hypolipidaemic drug probucol microcapsules fed daily for 4 weeks, to an insulin-resistant mouse model: potential hypoglycaemic and anti-inflammatory effects. Drug Deliv Transl Res 2018; 8(3): 543-51.
[http://dx.doi.org/10.1007/s13346-017-0473-5] [PMID: 29313296]
[http://dx.doi.org/10.1007/s13346-017-0473-5] [PMID: 29313296]
[16]
Mooranian A, Negrulj R, Takechi R, Jamieson E, Morahan G, Al-Salami H. Electrokinetic potential-stabilization by bile acid-microencapsulating formulation of pancreatic β-cells cultured in high ratio poly-L-ornithine-gel hydrogel colloidal dispersion: applications in cell-biomaterials, tissue engineering and biotechnological applications. Artif Cells Nanomed Biotechnol 2018; 46(6): 1156-62.
[http://dx.doi.org/10.1080/21691401.2017.1362416] [PMID: 28776395]
[http://dx.doi.org/10.1080/21691401.2017.1362416] [PMID: 28776395]
[17]
Mamo JC, Lam V, Brook E, Mooranian A, Al-Salami H, Fimognari N, et al. Probucol prevents blood-brain barrier dysfunction and cognitive decline in mice maintained on pro-diabetic diet. Diabetes & vascular disease research 2018. 1479164118795274
[18]
Mamo JC, Lam V, Al-Salami H, et al. Sodium alginate capsulation increased brain delivery of probucol and suppressed neuroinflammation and neurodegeneration. Ther Deliv 2018; 9(10): 703-9.
[http://dx.doi.org/10.4155/tde-2018-0033] [PMID: 30277134]
[http://dx.doi.org/10.4155/tde-2018-0033] [PMID: 30277134]
[19]
Takechi R, Lam V, Brook E, et al. Blood-brain barrier dysfunction precedes cognitive decline and neurodegeneration in diabetic insulin resistant mouse model: An implication for causal link. Front Aging Neurosci 2017; 9: 399.
[http://dx.doi.org/10.3389/fnagi.2017.00399] [PMID: 29249964]
[http://dx.doi.org/10.3389/fnagi.2017.00399] [PMID: 29249964]
[20]
Mooranian A, Tackechi R, Jamieson E, Morahan G, Al-Salami H. Innovative microcapsules for pancreatic β-cells harvested from mature double-transgenic mice: Cell imaging, viability, induced glucose-stimulated insulin measurements and proinflammatory cytokines analysis. Pharm Res 2017; 34(6): 1217-23.
[http://dx.doi.org/10.1007/s11095-017-2138-y] [PMID: 28289997]
[http://dx.doi.org/10.1007/s11095-017-2138-y] [PMID: 28289997]
[21]
Mooranian A, Negrulj R, Takechi R, Jamieson E, Morahan G, Al-Salami H. Alginate-combined cholic acid increased insulin secretion of microencapsulated mouse cloned pancreatic β cells. Ther Deliv 2017; 8(10): 833-42.
[http://dx.doi.org/10.4155/tde-2017-0042] [PMID: 28944743]
[http://dx.doi.org/10.4155/tde-2017-0042] [PMID: 28944743]
[22]
Mooranian A, Negrulj R, Takechi R, Jamieson E, Morahan G, Al-Salami H. Influence of biotechnological processes, speed of formulation flow and cellular concurrent stream-integration on insulin production from β-cells as a result of co-encapsulation with a highly lipophilic bile acid. Cell Mol Bioeng 2017; 11(1): 65-75.
[http://dx.doi.org/10.1007/s12195-017-0510-y] [PMID: 31719879]
[http://dx.doi.org/10.1007/s12195-017-0510-y] [PMID: 31719879]
[23]
Mooranian A, Negrulj R, Takechi R, Jamieson E, Morahan G, Al-Salami H. New biotechnological microencapsulating methodology utilizing individualized gradient-screened jet laminar flow techniques for pancreatic β-cell delivery: bile acids support cell energy-generating mechanisms. Mol Pharm 2017; 14(8): 2711-8.
[http://dx.doi.org/10.1021/acs.molpharmaceut.7b00220] [PMID: 28682620]
[http://dx.doi.org/10.1021/acs.molpharmaceut.7b00220] [PMID: 28682620]
[24]
Mooranian A, Negrulj R, Al-Salami H. The effects of ionic gelation- vibrational jet flow technique in fabrication of microcapsules incorporating β-cell: applications in diabetes. Curr Diabetes Rev 2017; 13(1): 91-6.
[http://dx.doi.org/10.2174/1573399812666151229101756] [PMID: 26710877]
[http://dx.doi.org/10.2174/1573399812666151229101756] [PMID: 26710877]
[25]
Mamo JCL, Lam V, Giles C, et al. Antihypertensive agents do not prevent blood-brain barrier dysfunction and cognitive deficits in dietary-induced obese mice. Int J Obes 2017; 41(6): 926-34.
[http://dx.doi.org/10.1038/ijo.2017.57] [PMID: 28239165]
[http://dx.doi.org/10.1038/ijo.2017.57] [PMID: 28239165]
[26]
Al-Salami H, Mamo JC, Mooranian A, et al. Long-term supplementation of microencapsulated ursodeoxycholic acid prevents hypertension in a mouse model of insulin resistance. experimental and clinical endocrinology & diabetes: official journal, german society of endocrinology. German Diabetes Association 2017; 125(1): 28-32.
[27]
Mooranian A, Negrulj R, Chen-Tan N, et al. Advanced bile acid-based multi-compartmental microencapsulated pancreatic β-cells integrating a polyelectrolyte-bile acid formulation, for diabetes treatment. Artif Cells Nanomed Biotechnol 2016; 44(2): 588-95.
[http://dx.doi.org/10.3109/21691401.2014.971806] [PMID: 25358121]
[http://dx.doi.org/10.3109/21691401.2014.971806] [PMID: 25358121]
[28]
Mooranian A, Negrulj R, Arfuso F, Al-Salami H. Multicompartmental, multilayered probucol microcapsules for diabetes mellitus: Formulation characterization and effects on production of insulin and inflammation in a pancreatic β-cell line. Artif Cells Nanomed Biotechnol 2016; 44(7): 1642-53.
[http://dx.doi.org/10.3109/21691401.2015.1069299] [PMID: 26377035]
[http://dx.doi.org/10.3109/21691401.2015.1069299] [PMID: 26377035]
[29]
Mooranian A, Negrulj R, Al-Salami H. Alginate-deoxycholic Acid Interaction and Its impact on pancreatic B-cells and insulin secretion and potential treatment of type 1 diabetes. J Pharm Innov 2016; 11(2): 156-61.
[http://dx.doi.org/10.1007/s12247-016-9248-7]
[http://dx.doi.org/10.1007/s12247-016-9248-7]
[30]
Mooranian A, Negrulj R, Al-Salami H. The influence of stabilized deconjugated ursodeoxycholic acid on polymer-hydrogel system of transplantable NIT-1 cells. Pharm Res 2016; 33(5): 1182-90.
[http://dx.doi.org/10.1007/s11095-016-1863-y] [PMID: 26818840]
[http://dx.doi.org/10.1007/s11095-016-1863-y] [PMID: 26818840]
[31]
Mooranian A, Negrulj R, Arfuso F, Al-Salami H. The effect of a tertiary bile acid, taurocholic acid, on the morphology and physical characteristics of microencapsulated probucol: potential applications in diabetes: a characterization study. Drug Deliv Transl Res 2015; 5(5): 511-22.
[http://dx.doi.org/10.1007/s13346-015-0248-9] [PMID: 26242686]
[http://dx.doi.org/10.1007/s13346-015-0248-9] [PMID: 26242686]
[32]
Mooranian A, Negrulj R, Al-Sallami HS, et al. Release and swelling studies of an innovative antidiabetic-bile acid microencapsulated formulation, as a novel targeted therapy for diabetes treatment. J Microencapsul 2015; 32(2): 151-6.
[http://dx.doi.org/10.3109/02652048.2014.958204] [PMID: 25265061]
[http://dx.doi.org/10.3109/02652048.2014.958204] [PMID: 25265061]
[33]
Mooranian A, Negrulj R, Chen-Tan N, Watts GF, Arfuso F, Al-Salami H. An optimized probucol microencapsulated formulation integrating a secondary bile acid (deoxycholic acid) as a permeation enhancer. Drug Des Devel Ther 2014; 8: 1673-83.
[PMID: 25302020]
[PMID: 25302020]
[34]
Mooranian A, Negrulj R, Chen-Tan N, et al. Microencapsulation as a novel delivery method for the potential antidiabetic drug, Probucol. Drug Des Devel Ther 2014; 8: 1221-30.
[PMID: 25246766]
[PMID: 25246766]
[35]
Mooranian A, Negrulj R, Chen-Tan N, et al. Novel artificial cell microencapsulation of a complex gliclazide-deoxycholic bile acid formulation: a characterization study. Drug Des Devel Ther 2014; 8: 1003-12.
[PMID: 25114507]
[PMID: 25114507]
[36]
Fakhoury M, Negrulj R, Mooranian A, Al-Salami H. Inflammatory bowel disease: clinical aspects and treatments. J Inflamm Res 2014; 7: 113-20.
[http://dx.doi.org/10.2147/JIR.S65979] [PMID: 25075198]
[http://dx.doi.org/10.2147/JIR.S65979] [PMID: 25075198]
[37]
Meinders AE, Van Berge Henegouwen GP, Willekens FL, Schwerzel AL, Ruben A, Huybregts AW. Biliary lipid and bile acid composition in insulin-dependent diabetes mellitus. Arguments for increased intestinal bacterial bile acid degradation. Dig Dis Sci 1981; 26(5): 402-8.
[http://dx.doi.org/10.1007/BF01313581] [PMID: 7018861]
[http://dx.doi.org/10.1007/BF01313581] [PMID: 7018861]
[38]
Wey HE, Yunker RL, Harris P, Subbiah MT. Effect of streptozotocin-induced diabetes in neonatal rat on bile acid pool changes in adult life: selective sensitivity in females. Biochem Med 1984; 31(2): 167-73.
[http://dx.doi.org/10.1016/0006-2944(84)90021-8] [PMID: 6372789]
[http://dx.doi.org/10.1016/0006-2944(84)90021-8] [PMID: 6372789]
[39]
Vincent RP, Omar S, Ghozlan S, et al. Higher circulating bile acid concentrations in obese patients with type 2 diabetes. Ann Clin Biochem 2013; 50(Pt 4): 360-4.
[http://dx.doi.org/10.1177/0004563212473450] [PMID: 23771134]
[http://dx.doi.org/10.1177/0004563212473450] [PMID: 23771134]
[40]
Sansome DJ, Xie C, Veedfald S, Horowitz M, Rayner CK, Wu T. Mechanism of glucose-lowering by metformin in type 2 diabetes:
Role of bile acids. Diabetes, Obesity and Metabolism.n/a(n/a)
[41]
Finelli C, Sommella L, Gioia S, La Sala N, Tarantino G. Should visceral fat be reduced to increase longevity? Ageing Res Rev 2013; 12(4): 996-1004.
[http://dx.doi.org/10.1016/j.arr.2013.05.007] [PMID: 23764746]
[http://dx.doi.org/10.1016/j.arr.2013.05.007] [PMID: 23764746]
[42]
Li W, Liu R, Li X, et al. Saxagliptin alters bile acid profiles and yields metabolic benefits in drug-naïve overweight or obese type 2 diabetes patient. J Diabetes 2019; 11(12): 982-92.
[http://dx.doi.org/10.1111/1753-0407.12956] [PMID: 31141297]
[http://dx.doi.org/10.1111/1753-0407.12956] [PMID: 31141297]
[43]
Qi Y, Jiang C, Cheng J, et al. Bile acid signaling in lipid metabolism: metabolomic and lipidomic analysis of lipid and bile acid markers linked to anti-obesity and anti-diabetes in mice. Biochim Biophys Acta 2015; 1851(1): 19-29.
[http://dx.doi.org/10.1016/j.bbalip.2014.04.008] [PMID: 24796972]
[http://dx.doi.org/10.1016/j.bbalip.2014.04.008] [PMID: 24796972]
[44]
Hou W, Meng X, Zhao W, et al. Elevated first-trimester total bile acid is associated with the risk of subsequent gestational diabetes. Sci Rep 2016; 6: 34070.
[http://dx.doi.org/10.1038/srep34070] [PMID: 27667090]
[http://dx.doi.org/10.1038/srep34070] [PMID: 27667090]
[45]
Gao J, Xu B, Zhang X, et al. Association between serum bile acid profiles and gestational diabetes mellitus: A targeted metabolomics study. Clin Chim Acta 2016; 459: 63-72.
[http://dx.doi.org/10.1016/j.cca.2016.05.026] [PMID: 27246871]
[http://dx.doi.org/10.1016/j.cca.2016.05.026] [PMID: 27246871]
[46]
Batzri S, Harmon JW, Schweitzer EJ, Toles R. Bile acid accumulation in gastric mucosal cells. Proc Soc Exp Biol Med 1991; 197(4): 393-9.
[http://dx.doi.org/10.3181/00379727-197-43272] [PMID: 1871149]
[http://dx.doi.org/10.3181/00379727-197-43272] [PMID: 1871149]
[47]
Kobayashi Y, Hara N, Sugimoto R, et al. The associations between circulating bile acids and the muscle volume in patients with non-alcoholic fatty liver disease (NAFLD). Intern Med 2017; 56(7): 755-62.
[http://dx.doi.org/10.2169/internalmedicine.56.7796] [PMID: 28381740]
[http://dx.doi.org/10.2169/internalmedicine.56.7796] [PMID: 28381740]
[48]
Corbett CL, Bartholomew TC, Billing BH, Summerfield JA. Urinary excretion of bile acids in cholestasis: evidence for renal tubular secretion in man. Clin Sci (Lond) 1981; 61(6): 773-80.
[http://dx.doi.org/10.1042/cs0610773] [PMID: 7297039]
[http://dx.doi.org/10.1042/cs0610773] [PMID: 7297039]
[49]
Summerfield JA, Cullen J, Barnes S, Billing BH. Evidence for renal control of urinary excretion of bile acids and bile acid sulphates in the cholestatic syndrome. Clin Sci Mol Med 1977; 52(1): 51-65.
[http://dx.doi.org/10.1042/cs0520051] [PMID: 606464]
[http://dx.doi.org/10.1042/cs0520051] [PMID: 606464]
[50]
Houten SM, Watanabe M, Auwerx J. Endocrine functions of bile acids. EMBO J 2006; 25(7): 1419-25.
[http://dx.doi.org/10.1038/sj.emboj.7601049] [PMID: 16541101]
[http://dx.doi.org/10.1038/sj.emboj.7601049] [PMID: 16541101]
[51]
Roberts MS, Magnusson BM, Burczynski FJ, Weiss M. Enterohepatic circulation: physiological, pharmacokinetic and clinical implications. Clin Pharmacokinet 2002; 41(10): 751-90.
[http://dx.doi.org/10.2165/00003088-200241100-00005] [PMID: 12162761]
[http://dx.doi.org/10.2165/00003088-200241100-00005] [PMID: 12162761]
[52]
Mikov M, Boni NS, Al-Salami H, et al. Bioavailability and hypoglycemic activity of the semisynthetic bile acid salt, sodium 3alpha,7alpha-dihydroxy-12-oxo-5beta-cholanate, in healthy and diabetic rats. Eur J Drug Metab Pharmacokinet 2007; 32(1): 7-12.
[http://dx.doi.org/10.1007/BF03190984] [PMID: 17479538]
[http://dx.doi.org/10.1007/BF03190984] [PMID: 17479538]
[53]
Woolbright BL, Li F, Xie Y, et al. Lithocholic acid feeding results in direct hepato-toxicity independent of neutrophil function in mice. Toxicol Lett 2014; 228(1): 56-66.
[http://dx.doi.org/10.1016/j.toxlet.2014.04.001] [PMID: 24742700]
[http://dx.doi.org/10.1016/j.toxlet.2014.04.001] [PMID: 24742700]
[54]
Matsubara T, Tanaka N, Sato M, et al. TGF-β-SMAD3 signaling mediates hepatic bile acid and phospholipid metabolism following lithocholic acid-induced liver injury. J Lipid Res 2012; 53(12): 2698-707.
[http://dx.doi.org/10.1194/jlr.M031773] [PMID: 23034213]
[http://dx.doi.org/10.1194/jlr.M031773] [PMID: 23034213]
[55]
Mooranian A, Negrulj R, Jamieson E, Morahan G, Al-Salami H. Biological assessments of encapsulated pancreatic beta-cells: their potential transplantation in diabetes. Cell Mol Bioeng 2016; 9(4): 530-7.
[http://dx.doi.org/10.1007/s12195-016-0441-z]
[http://dx.doi.org/10.1007/s12195-016-0441-z]
[56]
Melchior H, Kurch-Bek D, Mund M. The prevalence of gestational diabetes. Dtsch Arztebl Int 2017; 114(24): 412-8.
[PMID: 28669379]
[PMID: 28669379]
[57]
Ogura Y, Ayaki Y. Effect of diabetes on the metabolism of chenodeoxycholic acid in isolated perfused rat liver. Biol Chem Hoppe Seyler 1987; 368(7): 813-7.
[http://dx.doi.org/10.1515/bchm3.1987.368.2.813] [PMID: 3304341]
[http://dx.doi.org/10.1515/bchm3.1987.368.2.813] [PMID: 3304341]
[58]
Pellicciari R, Costantino G, Camaioni E, et al. Bile acid derivatives as ligands of the farnesoid X receptor. Synthesis, evaluation, and structure-activity relationship of a series of body and side chain modified analogues of chenodeoxycholic acid. J Med Chem 2004; 47(18): 4559-69.
[http://dx.doi.org/10.1021/jm049904b] [PMID: 15317466]
[http://dx.doi.org/10.1021/jm049904b] [PMID: 15317466]
[59]
Chen X, Yan L, Guo Z, et al. Chenodeoxycholic acid attenuates high-fat diet-induced obesity and hyperglycemia via the G protein-coupled bile acid receptor 1 and proliferator-activated receptor γ pathway. Exp Ther Med 2017; 14(6): 5305-12.
[http://dx.doi.org/10.3892/etm.2017.5232] [PMID: 29285057]
[http://dx.doi.org/10.3892/etm.2017.5232] [PMID: 29285057]
[60]
Teodoro JS, Rolo AP, Jarak I, Palmeira CM, Carvalho RA. The bile acid chenodeoxycholic acid directly modulates metabolic pathways in white adipose tissue in vitro: insight into how bile acids decrease obesity. NMR Biomed 2016; 29(10): 1391-402.
[http://dx.doi.org/10.1002/nbm.3583] [PMID: 27488269]
[http://dx.doi.org/10.1002/nbm.3583] [PMID: 27488269]
[61]
Khan AA, Chow EC, Porte RJ, Pang KS, Groothuis GM. The role of lithocholic acid in the regulation of bile acid detoxication, synthesis, and transport proteins in rat and human intestine and liver slices. Toxicol In Vitro 2011; 25(1): 80-90.
[http://dx.doi.org/10.1016/j.tiv.2010.09.011] [PMID: 20888898]
[http://dx.doi.org/10.1016/j.tiv.2010.09.011] [PMID: 20888898]
[62]
Chae SY, Jin CH, Shin JH, et al. Biochemical, pharmaceutical and therapeutic properties of long-acting lithocholic acid derivatized exendin-4 analogs. J Control Release 2010; 142(2): 206-13.
[http://dx.doi.org/10.1016/j.jconrel.2009.10.025] [PMID: 19900495]
[http://dx.doi.org/10.1016/j.jconrel.2009.10.025] [PMID: 19900495]
[63]
Martínez-Moya P, Romero-Calvo I, Requena P, et al. Dose-dependent antiinflammatory effect of ursodeoxycholic acid in experimental colitis. Int Immunopharmacol 2013; 15(2): 372-80.
[http://dx.doi.org/10.1016/j.intimp.2012.11.017] [PMID: 23246254]
[http://dx.doi.org/10.1016/j.intimp.2012.11.017] [PMID: 23246254]
[64]
Lukivskaya O, Patsenker E, Buko VU. Protective effect of ursodeoxycholic acid on liver mitochondrial function in rats with alloxan-induced diabetes: link with oxidative stress. Life Sci 2007; 80(26): 2397-402.
[http://dx.doi.org/10.1016/j.lfs.2007.02.042] [PMID: 17512017]
[http://dx.doi.org/10.1016/j.lfs.2007.02.042] [PMID: 17512017]
[65]
Lukivskaya O, Lis R, Egorov A, Naruta E, Tauschel HD, Buko VU. The protective effect of ursodeoxycholic acid in alloxan-induced diabetes. Cell Biochem Funct 2004; 22(2): 97-103.
[http://dx.doi.org/10.1002/cbf.1063] [PMID: 15027098]
[http://dx.doi.org/10.1002/cbf.1063] [PMID: 15027098]
[66]
Staels B, Kuipers F. Bile acid sequestrants and the treatment of type 2 diabetes mellitus. Drugs 2007; 67(10): 1383-92.
[http://dx.doi.org/10.2165/00003495-200767100-00001] [PMID: 17600387]
[http://dx.doi.org/10.2165/00003495-200767100-00001] [PMID: 17600387]
[67]
Hansen M, Sonne DP, Mikkelsen KH, Gluud LL, Vilsbøll T, Knop FK. Bile acid sequestrants for glycemic control in patients with type 2 diabetes: A systematic review with meta-analysis of randomized controlled trials. J Diabetes Complications 2017; 31(5): 918-27.
[http://dx.doi.org/10.1016/j.jdiacomp.2017.01.011] [PMID: 28238556]
[http://dx.doi.org/10.1016/j.jdiacomp.2017.01.011] [PMID: 28238556]