Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice

Tahara, Atsuo; Kurosaki, Eiji; Yokono, Masanori; Yamajuku, Daisuke; Kihara, Rumi; Hayashizaki, Yuka; Takasu, Toshiyuki; Imamura, Masakazu; Li, Qun; Tomiyama, Hiroshi; Kobayashi, Yoshinori; Noda, Atsushi; Sasamata, Masao; Shibasaki, Masayuki

doi:10.1016/j.ejphar.2013.05.014

Cited by 258 publications

(219 citation statements)

References 35 publications

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“…A previous study using diabetic model mice demonstrated that ipragliflozin improved hepatic steatosis [31]. The reduction of ALT and ALP levels in the current study might reflect some beneficial effect on the liver, although the current study population had almost normal serum levels of hepatic enzymes from the beginning of the study and therefore its clinical impact remains unclear.…”

Section: Discussionmentioning

confidence: 58%

Ameliorated pancreatic β cell dysfunction in type 2 diabetic patients treated with a sodium-glucose cotransporter 2 inhibitor ipragliflozin

Takahara

Shiraiwa²,

Matsuoka

et al. 2015

Endocr J

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Section: Discussionmentioning

confidence: 58%

Ameliorated pancreatic β cell dysfunction in type 2 diabetic patients treated with a sodium-glucose cotransporter 2 inhibitor ipragliflozin

Takahara

Shiraiwa²,

Matsuoka

et al. 2015

Endocr J

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“…Treatment with the SGLT inhibitor phlorizin in Psammomys obesus gerbils was shown to decrease islet inflammation, possibly related to the improvement in glucotoxicity (3). In type 2 diabetic mice, the SGLT2 inhibitor ipraglifloxin was shown to improve hyperglycemia, insulin secretion, hyperlipidemia, and liver levels of oxidative stress biomarkers and reduce markers of inflammation including IL-6, TNF-a, MCP-1, and CRP levels (80 …”

Section: Sodium-glucose Cotransporter 2 Inhibitorsmentioning

confidence: 99%

Anti-inflammatory Agents in the Treatment of Diabetes and Its Vascular Complications

et al. 2016

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The association between hyperglycemia and inflammation and vascular complications in diabetes is now well established. Antidiabetes drugs may alleviate inflammation by reducing hyperglycemia; however, the anti-inflammatory effects of these medications are inconsistent and it is unknown whether their beneficial metabolic effects are mediated via modulation of chronic inflammation. Recent data suggest that immunomodulatory treatments may have beneficial effects on glycemia, b-cell function, and insulin resistance. However, the mechanisms underlying their beneficial metabolic effects are not always clear, and there are concerns regarding the specificity, safety, and efficacy of immune-based therapies. Herein, we review the anti-inflammatory and metabolic effects of current antidiabetes drugs and of anti-inflammatory therapies that were studied in patients with type 2 diabetes. We discuss the potential benefit of using anti-inflammatory treatments in diabetes and important issues that should be addressed prior to implementation of such therapeutic approaches.The prevalence of diabetes is on the rise, with 415 million people affected worldwide according to recent data from the International Diabetes Federation (1). This number is predicted to increase further, with 642 million people expected to develop diabetes by 2040. While many factors are known to contribute to the development of diabetes and its complications, the involvement of the immune system in the pathogenesis of metabolic diseases has been gaining interest. It has long been appreciated that inflammation is central to the pathology of the pancreatic islet in type 1 diabetes. However, growing evidence suggests that inflammation also plays an important role in the pathogenesis of type 2 diabetes, including obesity-related insulin resistance, impaired insulin secretion, and diabetes-related vascular complications. Pioneering studies suggest that immunomodulatory treatments may improve glycemia, b-cell function, and/or insulin resistance in patients with type 2 diabetes (2,3). These studies constitute a proof of concept that chronic inflammation is implicated in the pathophysiology of type 2 diabetes, and therefore targeting inflammation may ameliorate diabetes, preventing its progression and vascular complications. However, the effects of immunomodulatory treatments are not limited to tissues involved in disease pathophysiology and thus might have unwarranted side effects. Moreover, current antidiabetes drugs may alleviate systemic and tissue-specific inflammation (4-12), and therefore the added value of using specific immunomodulatory treatments needs to be confirmed. Herein, we review the anti-inflammatory and metabolic effects of standard antidiabetes medications and of novel anti-inflammatory treatments. We further discuss issues that should be addressed prior to implementation of immune-based therapy in the treatment of diabetes.

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“…Dapagliflozin also suppressed apoptosis and decreased caspase-12 expression in cultured renal proximal tubular cells [41]. Also, Tahara et al, [42], have shown that, ipragliflozin can reduce plasma and liver levels of markers of oxidative stress and inflammation, with improving glycemic control in diabetic mice. On the other hand, Vallon et al, [43], have shown that SGLT2 knockout attenuated hyperglycemia and glomerular hyperfiltration, but not renal injury markers, oxidative stress or inflammation in streptozotocin-induced diabetes model.…”

Section: Discussionmentioning

confidence: 99%

Comparative Renal Protective Effects of Canagliflozin and Telmisartan in a Rat Model of Diabetic Nephropathy

Abdel-Wahab¹

2016

NRT

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IntroductionDiabetic nephropathy is a major microvascular complication of diabetes, affecting 20 % to 40 % of diabetic patients [1]. It is an independent risk factor for cardiovascular disease and is associated with increased morbidity and mortality [2]. The glucose-induced oxidative stress and persistent inflammatory condition can cause deleterious renal changes contributing to the pathophysiology of diabetic nephropathy [3]. Increased reactive oxygen species production and reduced availability of antioxidant mechanisms can influence the renal function and structure by modulating cell growth, apoptosis, and inflammatory responses [4]. Also, early diabetic nephropathy is associated with glomerular hyperfiltration, cytokine release and tissue proliferation, processes that have been linked to progression of the kidney disease [5,6].Inhibitors of the renin-angiotensin system inhibitors are commonly used to decrease glomerular hyperfiltration, reduce proteinuria and delay progression of diabetic nephropathy [7]. Telmisartan, a selective angiotensin receptor blocker have shown to provide renal benefit at all stages of nephropathy in diabetic patients [8,9]. Some investigators have shown that telmisartan also possesses anti-inflammatory and antioxidant properties [10]. However, blockade of the renin-angiotensin system does not completely arrest kidney disease progression and many patients pass to end-stage renal disease [7].Recently, selective Sodium Glucose Cotransporter 2 (SGLT2) inhibitors have been developed for use in patients with type 2 diabetes [11,12]. Canagliflozin is a selective SGLT2 inhibitor, developed for treatment type 2 diabetes, showing improved glycemic control, both as monotherapy and in combination with other antidiabetics [13,14]. More recently, treatments with SGLT2 inhibitors have been reported to prevent the features of diabetic nephropathy including glomerular hyperfiltration and mesangial matrix expansion in diabetic animal models [15,16]. Beyond their antihyperglycemic properties, use of SGLT2 inhibitors was associated with additional non-glycemic benefits including reduction in blood pressure, plasma Abdel-Wahab AF, et al., J Nephrol Renal Ther 2016 AbstractCanagliflozin is a new antidiabetic, SGLT2 inhibitor, that interfere with renal glucose reabsorption but its effect on renal structure and function has not been elucidated. So, we investigated the renal protective effects of canagliflozin in comparison with the angiotensin blocker, telmisartan, in a rat model of diabetic nephropathy. Sixty male Wistar rats were randomly divided into six groups. Group 1; non-diabetic controls, given only vehicles. Group 2; non-treated diabetic rats injected with nicotinamide and streptozotocin. Group 3 and 4; diabetic rats treated for 8 weeks with canagliflozin 20 and 40 mg/kg/day. Group 5 and 6; diabetic rats treated with telmisartan 5 and 10 mg/kg/day, respectively. Biochemical analysis included plasma glucose, HbA1c, urinary albumin excretion, BUN, serum creatinine, creatinine clearance, TNF-α, TGF-β...

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Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice

Cited by 258 publications

References 35 publications

Ameliorated pancreatic β cell dysfunction in type 2 diabetic patients treated with a sodium-glucose cotransporter 2 inhibitor ipragliflozin

Ameliorated pancreatic β cell dysfunction in type 2 diabetic patients treated with a sodium-glucose cotransporter 2 inhibitor ipragliflozin

Anti-inflammatory Agents in the Treatment of Diabetes and Its Vascular Complications

Comparative Renal Protective Effects of Canagliflozin and Telmisartan in a Rat Model of Diabetic Nephropathy

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Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice

Cited by 258 publications

References 35 publications

Ameliorated pancreatic &beta; cell dysfunction in type 2 diabetic patients treated with a sodium-glucose cotransporter 2 inhibitor ipragliflozin

Ameliorated pancreatic &beta; cell dysfunction in type 2 diabetic patients treated with a sodium-glucose cotransporter 2 inhibitor ipragliflozin

Anti-inflammatory Agents in the Treatment of Diabetes and Its Vascular Complications

Comparative Renal Protective Effects of Canagliflozin and Telmisartan in a Rat Model of Diabetic Nephropathy

Contact Info

Product

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Ameliorated pancreatic β cell dysfunction in type 2 diabetic patients treated with a sodium-glucose cotransporter 2 inhibitor ipragliflozin

Ameliorated pancreatic β cell dysfunction in type 2 diabetic patients treated with a sodium-glucose cotransporter 2 inhibitor ipragliflozin