Altered gene expression involved in insulin signaling pathway in type II diabetic osteoporosis rats model

Li, Baoxin; Liu, Yan; Ma, Jianxia; Li, Yukun

doi:10.1007/s12020-012-9757-1

Cited by 30 publications

(21 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This widely-used model effectively mimics type 2 diabetes [15–17]. As diabetes is mainly characterized by weight loss, high blood sugar and insulin resistance, we first confirmed that our rat model was a model of diabetes by examining the weights, blood sugar levels, and insulin sensitivity index (ISI) values of the animals.…”

Section: Resultsmentioning

confidence: 53%

“…However, in order to better simulate the results of diabetes mellitus (relatively reduced insulin secretion), we intraperitoneally injected rats with streptozotocin at a dose of 30 mg/kg. After 72 h, fasting plasma glucose of 7.8 mmol/L and reduced insulin sensitivity were observed, confirming the successful establishment of the model [15]. The rats not used for the model were fed a normal diet.…”

Section: Methodsmentioning

confidence: 75%

“…In this study, we used a rat model of type 2 diabetes mellitus combined with osteoporosis that was established through the use of intralipids and a small dose of streptozotocin. This model effectively mimics type 2 diabetes, and is widely used [15–17]. As for the age of the rats, three-month-old rats are sexually mature, six-month-old rats have mature bones, and 17-month-old rats are relatively old [61].…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Melatonin suppresses autophagy in type 2 diabetic osteoporosis

et al. 2016

View full text Add to dashboard Cite

Type 2 diabetes mellitus is often complicated by osteoporosis, a process which may involve osteoblast autophagy. As melatonin suppresses autophagy under certain conditions, we its investigated the effects on bone autophagy during diabetes. We first assessed different body parameters in a diabetic rat model treated with various concentrations of melatonin. Dynamic biomechanicalmeasurements, bone organization hard slice dyeing and micro-CT were used to observe the rat bone microstructure, and immunohistochemistry was used to determine levels of autophagy biomarkers. We also performed in vitro experiments on human fetal osteoblastic (hFOB1.19) cells cultured with high glucose, different concentrations of melatonin, and ERK pathway inhibitors. And we used Western blotting and immunofluorescence to measure the extent of osteogenesis and autophagy. We found that melatonin improved the bone microstructure in our rat diabetes model and reduced the level of autophagy(50 mg/kg was better than 100 mg/kg). Melatonin also enhanced osteogenesis and suppressed autophagy in osteoblasts cultured at high glucose levels (10 μM was better than 1 mM). This suggests melatonin may reduce the level of autophagy in osteoblasts and delay diabetes-induced osteoporosis by inhibiting the ERK signaling pathway.

show abstract

Section: Resultsmentioning

confidence: 53%

Section: Methodsmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Melatonin suppresses autophagy in type 2 diabetic osteoporosis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The rats were given an intraperitoneal injection of streptozotocin (STZ) at a dose of 30mg/kg. After 72 hours, fasting plasma glucose >7.8mmol/Land reduced insulin sensitivity were observed and the models were successfully established6. The rats not used for modeling were fed a normal diet.…”

Section: Methodsmentioning

confidence: 99%

Regulation of DMT1 on Bone Microstructure in Type 2 Diabetes

Zhang¹,

Meng²,

Yang³

2015

Int. J. Med. Sci.

View full text Add to dashboard Cite

Diabetic osteoporosis is gradually attracted people's attention. However, the process of bone microstructure changes in diabetic patients, and the exact mechanism of osteoblast iron overload are unclear. Therefore, the present study aimed to explore the function of DMT1 in the pathological process of diabetic osteoporosis. We build the type two diabetes osteoporosis models with SD rats and Belgrade rats, respectively. Difference expression of DMT1 was detected by using the method of immunohistochemistry and western blotting. Detection of bone microstructure and biomechanics and iron content for each group of samples. We found that DMT1 expression in type 2 diabetic rats was higher than that in normal rats. The bone biomechanical indices and bone microstructure in the rat model deficient in DMT1 was significantly better than that in the normal diabetic model. The loss of DMT1 can reduce the content of iron in bone. These findings indicate that DMT1 expression was enhanced in the bone tissue of type 2 diabetic rats, and plays an important role in the pathological process of diabetic osteoporosis. Moreover, DMT1 may be a potential therapeutic target for diabetic osteoporosis.

show abstract

“…A previous study from our group showed that the expression of IGF1 and IRS1 is decreased in type 2 diabetic osteoporotic rats [26]. Liu HC et al found that the transfection of recombinant plasmid pEGFP-N1-IGF1 alleviated osteoporosis in ovariectomized rats [5].…”

mentioning

confidence: 87%

Osteoblast Proliferation is Enhanced upon the Insulin Receptor Substrate 1 Overexpression via PI3K Signaling Leading to Down-regulation of NFκB and BAX Pathway

Xue

et al. 2014

Exp Clin Endocrinol Diabetes

View full text Add to dashboard Cite

The insulin receptor substrate 1 (IRS1) promotes bone formation via osteoblast proliferation mediated by PI3K/Akt signaling. A reduction in NFκB activity in osteoblasts results in an increase in bone formation. The NFκB signaling pathway leads to increased expression of BAX, which contributes to osteoblast apoptosis. The purpose of this study was to investigate the expression of recombinant plasmid enhanced green fluorescent protein-N1 (pEGFP-N1) that transferred IRS1 gene into osteoblasts in vitro and evaluate the effects of IRS1 overexpression on NFκBp65 and on BAX. Osteoblasts were transfected with pEGFP-N1 or pEGFP-N1 encoding wild-type IRS1 (pEGFP-N1-IRS1). Cell cycle analysis was performed using flow cytometry. The expression levels of NFκBp65 and BAX were measured by Western blotting. Our results revealed that overexpression of IRS1 stimulated osteoblast proliferation, as evidenced by an increase in the number of cells in the S phase compared to controls. IRS1 overexpression in osteoblasts activated the PI3K/Akt pathway, and inhibited expression of NFκBp65 and BAX. When osteoblasts transfected with pEGFP-N1-IRS1 were exposed to a PI3K inhibitor (LY294002), the effects of IRS1 overexpression were reversed. On the basis of our study, it seems that osteoblasts proliferated upon IRS1 overexpression due to inhibition of the NFκB pathway and downregulation of BAX through PI3K/Akt signaling.

show abstract

Altered gene expression involved in insulin signaling pathway in type II diabetic osteoporosis rats model

Cited by 30 publications

References 48 publications

Melatonin suppresses autophagy in type 2 diabetic osteoporosis

Melatonin suppresses autophagy in type 2 diabetic osteoporosis

Regulation of DMT1 on Bone Microstructure in Type 2 Diabetes

Osteoblast Proliferation is Enhanced upon the Insulin Receptor Substrate 1 Overexpression via PI3K Signaling Leading to Down-regulation of NFκB and BAX Pathway

Contact Info

Product

Resources

About