Investigation of the Mechanisms Involved in the High-Dose and Long-Term Acetyl Salicylic Acid Therapy of Type I Diabetic Rats

Jafarnejad, Akbar; Bathaie, S. Zahra; Nakhjavani, Manouchehr; Hassan, Mohammad

doi:10.1124/jpet.107.130914

Cited by 30 publications

(16 citation statements)

References 36 publications

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“…More recent clinical studies report that T2-diabetic patients showed a 40 mg/dl decrease in fasting plasma glucose levels and a 21% reduction in blood glucose levels during a mixedmeal tolerance test after only 2 weeks of aspirin treatment [38]. Additionally, diabetic rodents treated with aspirin for a short term (7 days) or long-term (45 days to 5 months) regimes display significantly decreased blood glucose and HbA1c levels, similar to our findings [39,49,50]. In contrast, a small clinical study showed that neither aspirin treatment nor ibuprofen reduced fasting blood glucose levels in T2-diabetic patients, however this study had a small number of subjects compared to other studies, making their results difficult to draw conclusions from [54].…”

Section: Resultssupporting

confidence: 80%

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Low Dose Aspirin Therapy Decreases Blood Glucose Levels but Does not Prevent Type I Diabetes-induced Bone Loss

Coe

Denison

McCabe

2011

Cell Physiol Biochem

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Backgroud: Diabetes is strongly associated with increased fracture risk. During T1-diabetes onset, levels of blood glucose and pro-inflammatory cytokines (including TNFα) are increased. At the same time, levels of osteoblast markers are rapidly decreased and stay decreased 40 days later at which point bone loss is clearly evident. Inflammation is known to suppress bone formation and induce bone loss. Previous co-culture studies indicate that diabetic bone is inflamed and diabetic bone marrow is capable of enhancing osteoblast death in vitro. Here we investigate a commonly used non-steroidal anti-inflammatory drug, aspirin, to prevent T1-diabetic bone loss in vivo. Methods: We induced diabetes in 16-week-old male C57BL/6 mice and administered aspirin in the drinking water. Results: Our results demonstrate that aspirin therapy reduced diabetic mouse non-fasting blood glucose levels to less than 400 mg/dl, but did not prevent trabecular and cortical bone loss. In control mice, aspirin treatment increased bone formation markers but did not affect markers of bone resorption or bone density/volume. In diabetic mice, bone formation markers and bone density/volume are decreased and unaltered by aspirin treatment. Bone resorption markers, however, are increased and 2-way ANOVA analysis demonstrates an interaction between aspirin treatment and diabetes (p<0.007). Aspirin treatment did not prevent the previously reported diabetes-induced marrow adiposity. Conclusion: Taken together, our results suggest that low dose aspirin therapy does not negatively impact bone density in control and diabetic mice, but could potentially increase bone resorption in T1-diabetic mice.

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Section: Resultssupporting

confidence: 80%

“…A commonly used anti-inflammatory drug, aspirin, is known to reduce diabetes related inflammation [37,38] and decrease blood glucose levels in T1-diabetic rats [39]. Aspirin binds and inhibits cyclooxygenase (COX) enzyme and decreases prostaglandin (PG) production [40].…”

Section: Introductionmentioning

confidence: 99%

Low Dose Aspirin Therapy Decreases Blood Glucose Levels but Does not Prevent Type I Diabetes-induced Bone Loss

Coe

Denison

McCabe

2011

Cell Physiol Biochem

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“…Both excessive and impaired HSP72 expression may disturb cell proliferation and function (Atalay et al 2009). Increased levels of HSP70 in human monocytes are observed in response to in vitro heat stress (Jafarnejad et al 2008;Vince et al 2009). …”

Section: Introductionmentioning

confidence: 99%

Increased serum HSP70 levels are associated with the duration of diabetes

Nakhjavani

Morteza

Khajeali

et al. 2010

Cell Stress and Chaperones

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105

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The evolutionary conserved family of heat shock proteins (HSP) is responsible for protecting cells against different types of stress, including oxidative stress. Although the levels of HSPs can be readily measured in blood serum, the levels of HSP70 in patients with different durations of diabetes have not been studied before. We quantified serum HSP70 levels in a healthy control group (n=36) and two groups of type 2 diabetic patients, defined as newly diagnosed diabetes (n=36) and patients with diabetes duration of more than 5 years (n=37). The clinical characteristics and biochemical parameters were evaluated in the studied population. We found that serum HSP70 levels were significantly higher in patients with diabetes when compared with controls (p<0.001) and it was higher in patients with disease for more than 5 years than in newly diagnosed patients (p<0.001). Serum HSP70 was inversely correlated with fasting blood sugar in patients with diabetes for more than 5 years (r=−0.500, p=0.002), positively correlated with the history of hypertension in newly diagnosed patients (p<0.001), and positively correlated with age in patients with diabetes (r=0.531, p=0.001). Serum level of HSP70 is significantly higher in patients with diabetes and correlates with the duration of disease. Higher HSP70 in prolonged diabetes versus newly diagnosed diabetes may be an indicator of metabolic derangement in the course of diabetes.

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“…10) On one hand, there were studies suggesting that some non-steroidal anti-inflammatory drugs (NSAIDs) are effective in the treatment of type 1 diabetes, such as lisofylline (LSF), 11) pentoxifylline (PTX) 12) and aspirin. [13][14][15][16][17] Ibuprofen (IBU), also a NSAID, was reported to have the capacity of controlling blood glucose concentration and promoting glucose tolerance.…”

Section: Synthesis Of Diosgenin-ibuprofen Derivatives and Their Activmentioning

confidence: 99%

“…[13][14][15][16][17] Ibuprofen (IBU), also a NSAID, was reported to have the capacity of controlling blood glucose concentration and promoting glucose tolerance.…”

mentioning

confidence: 99%

Synthesis of Diosgenin-Ibuprofen Derivatives and Their Activities against Insulin-Dependent Diabetes Mellitus

Xin

Wang

Guo

et al. 2013

CHEMICAL & PHARMACEUTICAL BULLETIN

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The synthesis and anti-diabetes activities of diosgenin-ibuprofen derivatives were investigated. Ibuprofen (IBU) was chemically coupled with diosgenin either directly or through amino acid esters linkers. The effects of these compounds on lipopolysaccharide (LPS)-induced nitric oxide (NO) generation were assessed. The results showed spirost-5-en-3β-yl (2-(4-isobutyl-phenyl)-propionate) (4) was of better activity to suppress the production of NO in the supernatant of LPS-stimulated RAW264.7 cells. In vivo investigation on nonobese diabetic (NOD) mice indicated that compound 4 decreased the incidence of insulin-dependent diabetes mellitus (IDDM; type 1 diabetes) of NOD mice which suggested a potential activity of compound 4 against type 1 diabetes.Key words diosgenin-ibuprofen; nitric oxide generation; type 1 diabetes Diabetes mellitus (DM) is a common but complicated metabolic disease characterized by hyperglycemia. Insulin-dependent diabetes mellitus (IDDM; type 1 diabetes) results from the damage of the insulin-secreting β-cells in the pancreas through an autoimmune process, leading to permanent deficiency of endogenous insulin. [1][2][3] Although patients with this form of diabetes could depend on exogenous insulin to sustain life, serious complications such as cardiovascular diseases, blindness, kidney failure and stroke caused by hyperglycemia will lead to a high fatality rate.4-6) Therefore, applying processes or compounds that can strictly control the level of blood glucose or protect islet β-cells against destruction may be an alternative way to treat type 1 diabetes.Proinflammatory cytokines are cytotoxic to β-cells and have been implicated in the pathogenesis of type 1 diabetes. [7][8][9] Insulin which is the primary medication used to treat the diabetes and prevent complications in all DM patients suppresses the inflammatory process of type 1 diabetes through preventing hyperglycemia and modulating key inflammatory molecules.10) On one hand, there were studies suggesting that some non-steroidal anti-inflammatory drugs (NSAIDs) are effective in the treatment of type 1 diabetes, such as lisofylline (LSF), 11) pentoxifylline (PTX) 12) and aspirin. [13][14][15][16][17] Ibuprofen (IBU), also a NSAID, was reported to have the capacity of controlling blood glucose concentration and promoting glucose tolerance.13) It becomes toxic only at very high doses and has a wide therapeutic window.18) The anti-inflammatory activities of IBU were connected with the inhibition of cyclooxygenase enzymes, which reduce the synthesis of prostaglandins. It has also an inhibitory effect on the inducible nitric oxide synthase (iNOS) protein which diminishes the synthesis of the proinflammatory cytokines.19-21) On the other hand, steroidal anti-inflammatory drugs (SAIDS) could induce apoptosis or cell death of inflammatory cells and inhibit the production of inflammatory cytokines which are involved in the regulation of glucose metabolism and β-cell secretion.22) Diosgenin, an aglycone of steroidal saponins, possesses a variety o...

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Investigation of the Mechanisms Involved in the High-Dose and Long-Term Acetyl Salicylic Acid Therapy of Type I Diabetic Rats

Cited by 30 publications

References 36 publications

Low Dose Aspirin Therapy Decreases Blood Glucose Levels but Does not Prevent Type I Diabetes-induced Bone Loss

Low Dose Aspirin Therapy Decreases Blood Glucose Levels but Does not Prevent Type I Diabetes-induced Bone Loss

Increased serum HSP70 levels are associated with the duration of diabetes

Synthesis of Diosgenin-Ibuprofen Derivatives and Their Activities against Insulin-Dependent Diabetes Mellitus

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