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Current Diabetes Reviews

Author(s): Pedro Henrique Justino Oliveira Limirio, Nilson Ferreira De Oliveira Neto, Jessyca Figueira Venâncio, Camila Rodrigues Borges Linhares, Priscilla Barbosa Ferreira Soares and Paula Dechichi*

DOI: 10.2174/0115733998270859231117091741

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Insulin Therapy on Bone Macroscopic, Microarchitecture, and Mechanical Properties of Tibia in Diabetic Rats

Article ID: e030124225214 Pages: 6

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Abstract

Background: This study evaluated tibia's macroscopic structure, mechanical properties, and bone microarchitecture in rats with type 1 diabetes mellitus (T1DM).

Methods: Eighteen animals were divided into three groups (n=6): Non-diabetic (ND), diabetic (D), and diabetic+insulin (DI). T1DM was induced by streptozotocin; insulin was administered daily (4IU). The animals were euthanized 35 days after induction. The tibiae were removed and analyzed using macroscopic, micro-computed tomography (micro-CT) and three-point bending. The macroscopic analysis measured proximal-distal length (PD), antero-posterior thickness (AP) of proximal (AP-P) and distal (AP-D) epiphysis, and lateral-medial thickness (LM) of proximal (LM-P) and distal (LM-D) epiphysis. Micro-CT analysis closed porosity, tissue mineral density, and cortical thickness. The three-point bending test measured maximum strength, energy, and stiffness.

Results: The macroscopic analysis showed that D presented smaller measures of length and thickness (AP and AP-P) than ND and DI. More extensive measurements were observed of LM and AP-D thickness in DI than in D. In micro-CT, DI showed larger cortical thickness than D. Mechanical analysis showed lower strength in D than in other groups.

Conclusions: T1DM reduces bone growth and mechanical strength. Insulin therapy in diabetic rats improved bone growth and fracture resistance, making diabetic bone similar to normoglycemic animals.

[1]
Hadjidakis DJ, Androulakis I. Bone remodeling. Ann N Y Acad Sci 2006; 1092(1): 385-96.
[http://dx.doi.org/10.1196/annals.1365.035] [PMID: 17308163]
[2]
American Diabetes Association Diagnosis and classification of diabetes mellitus. Diabetes Care 2010; 33 (Suppl. 1): S62-9.
[PMID: 20042775]
[3]
Testa R, Bonfigli A, Genovese S, De Nigris V, Ceriello A. The possible role of flavonoids in the prevention of diabetic complications. Nutrients 2016; 8(5): 310.
[http://dx.doi.org/10.3390/nu8050310] [PMID: 27213445]
[4]
Wang LX, Jiang HL, Du SL. Observed impacts of insulin therapy on callus cell transforming growth factor-beta 1 expression in diabetic rats. Genet Mol Res 2015; 14(2): 5076-84.
[http://dx.doi.org/10.4238/2015.May.12.10] [PMID: 26125699]
[5]
Limirio PHJO, da Rocha Junior HA, Morais RB, et al. Influence of hyperbaric oxygen on biomechanics and structural bone matrix in type 1 diabetes mellitus rats. PLoS One 2018; 13(2): e0191694.
[http://dx.doi.org/10.1371/journal.pone.0191694] [PMID: 29451877]
[6]
Lecka-Czernik B. Diabetes, bone and glucose-lowering agents: Basic biology. Diabetologia 2017; 60(7): 1163-9.
[http://dx.doi.org/10.1007/s00125-017-4269-4] [PMID: 28434032]
[7]
Fulzele K, Clemens TL. Novel functions for insulin in bone. Bone 2012; 50(2): 452-6.
[http://dx.doi.org/10.1016/j.bone.2011.06.018] [PMID: 21723973]
[8]
Hou JCH, Zernicke RF, Barnard RJ. Effects of severe diabetes and insulin on the femoral neck of the immature rat. J Orthop Res 1993; 11(2): 263-71.
[http://dx.doi.org/10.1002/jor.1100110214] [PMID: 8483039]
[9]
Nyman JS, Kalaitzoglou E, Clay Bunn R, Uppuganti S, Thrailkill KM, Fowlkes JL. Preserving and restoring bone with continuous insulin infusion therapy in a mouse model of type 1 diabetes. Bone Rep 2017; 7: 1-8.
[http://dx.doi.org/10.1016/j.bonr.2017.07.001] [PMID: 28736738]
[10]
Rocha FS, Limirio PHJO, Zanetta-Barbosa D, Batista JD, Dechichi P. The effects of ionizing radiation on the growth plate in rat tibiae. Microsc Res Tech 2016; 79(12): 1147-51.
[http://dx.doi.org/10.1002/jemt.22769] [PMID: 27589341]
[11]
Irie MS, Rabelo GD, Spin-Neto R, Dechichi P, Borges JS, Soares PBF. Use of micro-computed tomography for bone evaluation in dentistry. Braz Dent J 2018; 29(3): 227-38.
[http://dx.doi.org/10.1590/0103-6440201801979] [PMID: 29972447]
[12]
Aeimlapa R, Wongdee K, Charoenphandhu N, Suntornsaratoon P, Krishnamra N. Premature chondrocyte apoptosis and compensatory upregulation of chondroregulatory protein expression in the growth plate of Goto–Kakizaki diabetic rats. Biochem Biophys Res Commun 2014; 452(3): 395-401.
[http://dx.doi.org/10.1016/j.bbrc.2014.08.085] [PMID: 25159845]
[13]
Rőszer T, Józsa T, Kiss-Tóth ÉD, De Clerck N, Balogh L. Leptin receptor deficient diabetic (db/db) mice are compromised in postnatal bone regeneration. Cell Tissue Res 2014; 356(1): 195-206.
[http://dx.doi.org/10.1007/s00441-013-1768-6] [PMID: 24343796]
[14]
Katyayan PA, Katyayan M, Shah RJ. Rehabilitative considerations for dental implants in the diabetic patient. J Indian Prosthodont Soc 2013; 13(3): 175-83.
[PMID: 24431731]
[15]
Sanguineti R, Storace D, Monacelli F, Federici A, Odetti P. Pentosidine effects on human osteoblasts in vitro. Ann N Y Acad Sci 2008; 1126(1): 166-72.
[http://dx.doi.org/10.1196/annals.1433.044] [PMID: 18448811]
[16]
Iyer S, Han L, Ambrogini E, et al. Deletion of Foxo1, 3, and 4 in osteoblast progenitors attenuates the loss of cancellous bone mass in a mouse model of type 1 diabetes. J Bone Miner Res 2017; 32(1): 60-9.
[http://dx.doi.org/10.1002/jbmr.2934] [PMID: 27491024]
[17]
Thrailkill KM, Lumpkin CK Jr, Bunn RC, Kemp SF, Fowlkes JL. Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues. Am J Physiol Endocrinol Metab 2005; 289(5): E735-45.
[http://dx.doi.org/10.1152/ajpendo.00159.2005] [PMID: 16215165]
[18]
Fulzele K, Riddle RC, DiGirolamo DJ, et al. Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell 2010; 142(2): 309-19.
[http://dx.doi.org/10.1016/j.cell.2010.06.002] [PMID: 20655471]
[19]
Thrailkill K, Bunn RC, Lumpkin C Jr, et al. Loss of insulin receptor in osteoprogenitor cells impairs structural strength of bone. J Diabetes Res 2014; 2014: 1-9.
[http://dx.doi.org/10.1155/2014/703589] [PMID: 24963495]
[20]
Osima M, Kral R, Borgen TT, et al. Women with type 2 diabetes mellitus have lower cortical porosity of the proximal femoral shaft using low-resolution CT than nondiabetic women, and increasing glucose is associated with reduced cortical porosity. Bone 2017; 97: 252-60.
[http://dx.doi.org/10.1016/j.bone.2017.01.037] [PMID: 28161589]
[21]
Rubin MR. Skeletal fragility in diabetes. Ann N Y Acad Sci 2017; 1402(1): 18-30.
[http://dx.doi.org/10.1111/nyas.13463] [PMID: 28926113]
[22]
Hernandez CJ, Tang SY, Baumbach BM, et al. Trabecular microfracture and the influence of pyridinium and non-enzymatic glycation-mediated collagen cross-links. Bone 2005; 37(6): 825-32.
[http://dx.doi.org/10.1016/j.bone.2005.07.019] [PMID: 16140600]
[23]
Saito M, Fujii K, Soshi S, Tanaka T. Reductions in degree of mineralization and enzymatic collagen cross-links and increases in glycation-induced pentosidine in the femoral neck cortex in cases of femoral neck fracture. Osteoporos Int 2006; 17(7): 986-95.
[http://dx.doi.org/10.1007/s00198-006-0087-0] [PMID: 16552468]
[24]
Huebschmann AG, Regensteiner JG, Vlassara H, Reusch JEB. Diabetes and advanced glycoxidation end products. Diabetes Care 2006; 29(6): 1420-32.
[http://dx.doi.org/10.2337/dc05-2096] [PMID: 16732039]
[25]
Follak N, Klöting L, Wolf E, Merk H. Delayed remodeling in the early period of fracture healing in spontaneously diabetic BB/OK rats depending on the diabetic metabolic state. Histol Histopathol 2004; 19(2): 473-86.
[PMID: 15024708]