Citation: | LAN Ya, LI Xiao, YANG Maoqin, DU Peng, HUAN Wei, WU Jingmei, CHENG Jiamao. Canagliflozin versus soy isoflavone for bone metabolism in model rats with type 1 diabetes mellitus[J]. Journal of Clinical Medicine in Practice, 2023, 27(5): 85-91. DOI: 10.7619/jcmp.20223475 |
To compare the effect of canagliflozin (CGLZ) and soy isoflavone (SIF) on bone metabolism in model rats with type 1 diabetes mellitus.
Forty male SD rats were randomly divided into control group, model group, SIF group, low-dose CGLZ group and high-dose CGLZ group, with 8 rats in each group. Model group and treatment groups were intraperitoneally injected with streptozotocin for modeling. The rats in treatment groups were gavaged daily for 12 weeks. During and after treatment, the body mass, food intake, water consumption, fasting blood glucose (FPG), serum albumin (ALB), serum calcium (SCa), serum phosphorus (SP), serum creatinine (Scr), serum 25 hydroxyvitamin D (25-OH-D3), urine protein (Pro), urine creatinine (Ucr), urine protein to urine creatinine ratio (UPCR) and bone metabolism related indicators[total bone mineral density (TBMD), regional bone mineral density (RBMD), total body salt content (TBSC), total body fat mass (TBFM) and total body muscle mass (TBMM)]of rats in each group were detected. Detection sites of RBMD included head, upper limb, thigh, trunk, rib, pelvis and spine.
After 12 weeks of successful modeling, the water intake and food consumption of rats in model group, SIF group, low-dose CGLZ group and high-dose CGLZ group all increased, while the body mass decreased; after medication, the body mass of rats in low-dose CGLZ group and high-dose CGLZ group increased, and increased range of body mass in high-dose CGLZ group was significantly greater than that in the SIF group. The FPG level of rats after 4 weeks of treatment in low-dose CGLZ group and high-dose CGLZ group as well as after 8 and 12 weeks of treatment in the SIF group, low-dose CGLZ group and high-dose CGLZ group decreased, and efficacy ranking from high to low was high-dose CGLZ group, low-dose CGLZ group and SIF group. After 12 weeks of treatment, Pro, Ucr and UPCR of rats in each treatment group decreased significantly (P < 0.01); in the SIF group, low-dose CGLZ group and high-dose CGLZ group, serum ALB level increased significantly while Scr level decreased significantly(P < 0.01); the level of 25-OH-D3 in high-dose CGLZ group decreased significantly (P < 0.01). After treatment of 12 weeks, TBSC in high-dose CGLZ group increased, but TBMD, TBSC, TBFM and TBMM did not increase in SIF group and low-dose CGLZ group; the increase of bone mineral density was observed in the thigh of high-dose CGLZ group, the trunk, ribs and spine of low-dose CGLZ group and high-dose CGLZ group, and the pelvis of SIF group and high-dose CGLZ group.
Both CGLZ and SIF can reduce hyperglycemia induced by streptozotocin in model rats with type 1 diabetes mellitus, and the effect of the former is better. In terms of improving the total body bone salts, total body bone mineral density and bone mineral density at all sites, the effect of high-dose CGLZ is better than that of low-dose CGLZ, while SIF can only improve the bone mineral density of pelvis to a certain extent.
[1] |
NINCEVIC V, OMANOVIC KOLARIC T, ROGULJIC H, et al. Renal benefits of SGLT 2 inhibitors and GLP-1 receptor agonists: evidence supporting a paradigm shift in the medical management of type 2 diabetes[J]. Int J Mol Sci, 2019, 20(23): 5831. doi: 10.3390/ijms20235831
|
[2] |
CHILTON R J. Effects of sodium-glucose cotransporter-2 inhibitors on the cardiovascular and renal complications of type 2 diabetes[J]. Diabetes Obes Metab, 2020, 22(1): 16-29. doi: 10.1111/dom.13854
|
[3] |
NEAL B, PERKOVIC V, MAHAFFEY K W, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes[J]. N Engl J Med, 2017, 377(7): 644-657. doi: 10.1056/NEJMoa1611925
|
[4] |
PERKOVIC V, JARDINE M J, NEAL B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy[J]. N Engl J Med, 2019, 380(24): 2295-2306. doi: 10.1056/NEJMoa1811744
|
[5] |
KIM I S. Current perspectives on the beneficial effects of soybean isoflavones and their metabolites for humans[J]. Antioxidants (Basel), 2021, 10(7): 1064. doi: 10.3390/antiox10071064
|
[6] |
雷作熹, 罗仁, 董晓蕾, 等. STZ诱导糖尿病肾病大鼠模型的建立[J]. 中国实验动物学报, 2005, 13(3): 163-165, 197. doi: 10.3969/j.issn.1005-4847.2005.03.010
|
[7] |
李荣霏, 曹春芽, 刘志华. 大豆异黄酮对糖尿病大鼠肾脏的保护作用及其机制[J]. 中南药学, 2014, 12(6): 532-534. https://www.cnki.com.cn/Article/CJFDTOTAL-ZNYX201406009.htm
|
[8] |
洪文娟, 邹久林, 余卓锐, 等. SGLT2i对肾病综合征模型大鼠骨代谢的影响[J]. 大理大学学报, 2022, 7(4): 21-25. https://www.cnki.com.cn/Article/CJFDTOTAL-DLSZ202204004.htm
|
[9] |
EL HAGE L, KASHYAP S R, RAO P. Use of SGLT-2 inhibitors in patients with type 1 diabetes mellitus[J]. J Prim Care Community Health, 2019, 10: 2150132719895188.
|
[10] |
KOHLER S, SALSALI A, HANTEL S, et al. Safety and tolerability of empagliflozin in patients with type 2 diabetes[J]. Clin Ther, 2016, 38(6): 1299-1313. doi: 10.1016/j.clinthera.2016.03.031
|
[11] |
DONG B Z, LV R L, WANG J, et al. The extraglycemic effect of SGLT-2is on mineral and bone metabolism and bone fracture[J]. Front Endocrinol (Lausanne), 2022, 13: 918350. doi: 10.3389/fendo.2022.918350
|
[12] |
POIANA C, CAPATINA C. Fracture risk assessment in patients with diabetes mellitus[J]. J Clin Densitom, 2017, 20(3): 432-443. doi: 10.1016/j.jocd.2017.06.011
|
[13] |
JACKSON K, MOSELEY K F. Diabetes and bone fragility: SGLT2 inhibitor use in the context of renal and cardiovascular benefits[J]. Curr Osteoporos Rep, 2020, 18(5): 439-448. doi: 10.1007/s11914-020-00609-z
|
[14] |
THRAILKILL K M, BUNN R C, UPPUGANTI S, et al. Canagliflozin, an SGLT2 inhibitor, corrects glycemic dysregulation in TallyHO model of T2D but only partially prevents bone deficits[J]. Bone, 2020, 141: 115625. doi: 10.1016/j.bone.2020.115625
|
[15] |
TANG H L, LI D D, ZHANG J J, et al. Lack of evidence for a harmful effect of sodium-glucose co-transporter 2 (SGLT2) inhibitors on fracture risk among type 2 diabetes patients: a network and cumulative meta-analysis of randomized controlled trials[J]. Diabetes Obes Metab, 2016, 18(12): 1199-1206. doi: 10.1111/dom.12742
|
[16] |
ZHANG Y S, ZHENG Y D, YUAN Y, et al. Effects of anti-diabetic drugs on fracture risk: a systematic review and network meta-analysis[J]. Front Endocrinol (Lausanne), 2021, 12: 735824. doi: 10.3389/fendo.2021.735824
|
[17] |
CASTELO-BRANCO C, SOVERAL I. Phytoestrogens and bone health at different reproductive stages[J]. Gynecol Endocrinol, 2013, 29(8): 735-743. doi: 10.3109/09513590.2013.801441
|
[18] |
NAKAI S, FUJITA M, KAMEI Y. Health promotion effects of soy isoflavones[J]. J Nutr Sci Vitaminol (Tokyo), 2020, 66(6): 502-507. doi: 10.3177/jnsv.66.502
|
[19] |
LI J S, YANG M, LI Y N, et al. Chloroplast genomes of two Pueraria DC. species: sequencing, comparative analysis and molecular marker development[J]. FEBS Open Bio, 2022, 12(2): 349-361. doi: 10.1002/2211-5463.13335
|
[20] |
DAS D, SARKAR S, DIHINGIA A, et al. A popular fermented soybean food of Northeast India exerted promising antihyperglycemic potential via stimulating PI3K/AKT/AMPK/GLUT4 signaling pathways and regulating muscle glucose metabolism in type 2 diabetes[J]. J Food Biochem, 2022, 46(12): e14385.
|
[21] |
WEI P, LIU M, CHEN Y, et al. Systematic review of soy isoflavone supplements on osteoporosis in women[J]. Asian Pac J Trop Med, 2012, 5(3): 243-248. doi: 10.1016/S1995-7645(12)60033-9
|
[22] |
MENGHINI L, FERRANTE C, LEPORINI L, et al. A natural formula containing lactoferrin, Equisetum arvensis, soy isoflavones and vitamin D3 modulates bone remodeling and inflammatory markers in young and aged rats[J]. J Biol Regul Homeost Agents, 2016, 30(4): 985-996.
|
[23] |
CHANG K L, HU Y C, HSIEH B S, et al. Combined effect of soy isoflavones and vitamin D3 on bone loss in ovariectomized rats[J]. Nutrition, 2013, 29(1): 250-257. doi: 10.1016/j.nut.2012.03.009
|
[24] |
TAKU K, MELBY M K, NISHI N, et al. Soy isoflavones for osteoporosis: an evidence-based approach[J]. Maturitas, 2011, 70(4): 333-338.
|