ABSTRACT
Hyperglycemia enhances bone resorption and impairment. Controlling blood glucose via metformin benefits bonecells. Hyperglycemia enhances basal phosphorylation of p38 mitogen-activated protein kinase (MAPK), whichaggravates bone resorption. Therefore, the aim of this study was to assess the osteoprotective effects of metformin andp38 MAPK inhibitor in non-obese T2DM rats. In this study, non-obese T2DM (Goto-kakizaki, GK) rats were dividedinto four groups, including DM group, metformin treatment, SB203580 treatment, and metformin combined withSB203580. Wistar rats were used as control group. Femur, tibia, and iliac rat bones were collected to determine boneporosity via synchrotron radiation microtomography. Primary osteoblasts were isolated from calvaria to investigatecell proliferation and osteoblast function, including alkaline phosphatase (ALP) expression and calcium deposition.The results showed that diabetes increase bone porosity. Treatment with metformin significantly reduced porosity intrabecular and cortical bone of the femur, tibia, and iliac, while SB203580 significantly reduced porosity in corticalbone. A combination group showed significantly reduced bone porosity only in trabecular bone of the femur. Isolatedosteoblasts showed lower growth rates. Treatment with metformin significantly increased cell proliferation, ALPexpression, and calcium deposition. In summary, metformin treatment improved bone quality by reducing boneporosity, increasing cell proliferation, and improving osteoblast characteristics.
ABSTRACT
Diabetic complications caused by hyperglycemia and oxidative stress, which can activate p38 mitogen-activatedprotein kinase (p38 MAPK), and aggravate complications via the enhancement of reactive oxygen species (ROS)generation. Recently, metformin or p38 MAPK inhibitors could reduce ROS production in particularly proteincarbonylation, in diabetic vessel. However, the combinatorial effect of metformin and SB203580 on internal organoxidative stress in non-obese (lean) type 2 diabetes mellitus (T2DM) is still uncleared. In this study, Goto-Kakizakirats were divided into four groups, including control diabetic group, metformin-treated group, p38 MAPK inhibitor(SB203580)-treated group, and combination between metformin and p38 MAPK inhibitor (SB203580). Internal organprotein from kidney, pancreas, liver, and brain was determined for protein carbonyl (PC) content by spectrophotometric2, 4-Dinitrophenylhydrazine assay. There was an increase in PC content levels in the serum and internal organs ofT2DM. Metformin ameliorated PC content in serum and internal organs. However, SB203580 could only reduce thePC content in the liver. The combination of metformin and SB203580 could synergistically reduce the PC contentlevels in serum but not the internal organs. In summary, metformin provided the greatest potential for reducingoxidative stress, while SB203580 or combined metformin with SB203580 could not reduce oxidative stress in theinternal organs of non-obese type 2 diabetic rats.
ABSTRACT
Diabetic complications may in part be due to inflammation. Diabetes can also develop in non-obese people.Nonetheless, organ inflammation in non-obese type 2 diabetes mellitus animals has never been investigated. The GotoKakizaki rats were divided into two groups: diabetes and diabetes treated with metformin. The glycemia parameterswere then determined. Serum and internal organs, including the liver, kidney, and brain were collected to determinethe levels of inflammatory cytokine and mRNA expression. The research found an increase in interleukin-6 (IL-6)and IL-1β cytokine levels in the liver of the diabetic group, which corresponds with the mRNA expression of bothcytokines. The metformin group significantly reduces the mRNA expression of liver IL-6. In the kidney, there was anincrease in IL-6 cytokine levels in the diabetic group, while the metformin group could reduce the mRNA expressionlevel of tumor necrosis factor α (TNF-α). In addition, there were IL-6 and TNF-α cytokines level increased in thebrain of the diabetic group. IL-1β mRNA expression levels increased in the diabetic group and were reduced by themetformin treatment. The metformin treatment reduced serum TNF-α cytokines. In summary, this study demonstratedthat internal organ inflammation in non-obese diabetic rats, which could provide evidence for organ inflammation,may potentially explain diabetic complications.
ABSTRACT
Diabetic complications may in part be due to inflammation. Diabetes can also develop in non-obese people.Nonetheless, organ inflammation in non-obese type 2 diabetes mellitus animals has never been investigated. The GotoKakizaki rats were divided into two groups: diabetes and diabetes treated with metformin. The glycemia parameterswere then determined. Serum and internal organs, including the liver, kidney, and brain were collected to determinethe levels of inflammatory cytokine and mRNA expression. The research found an increase in interleukin-6 (IL-6)and IL-1β cytokine levels in the liver of the diabetic group, which corresponds with the mRNA expression of bothcytokines. The metformin group significantly reduces the mRNA expression of liver IL-6. In the kidney, there was anincrease in IL-6 cytokine levels in the diabetic group, while the metformin group could reduce the mRNA expressionlevel of tumor necrosis factor α (TNF-α). In addition, there were IL-6 and TNF-α cytokines level increased in thebrain of the diabetic group. IL-1β mRNA expression levels increased in the diabetic group and were reduced by themetformin treatment. The metformin treatment reduced serum TNF-α cytokines. In summary, this study demonstratedthat internal organ inflammation in non-obese diabetic rats, which could provide evidence for organ inflammation,may potentially explain diabetic complications.