Effect of pitavastatin on type 2 diabetes mellitus nephropathy in KK-Ay/Ta mice

Matsumoto, Mitsuhito; Tanimoto, Masuhisa; Gohda, Tomohito; Aoki, Tatsuya; Murakoshi, Maki; Yamada, Kaori; Yamazaki, Takahiko; Kaneko, Shigeru; Horikoshi, Satoshi; Tomino, Yasuhiko

doi:10.1016/j.metabol.2008.01.007

Cited by 29 publications

(27 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…54 The histological changes observed in the kidneys of KK-Ay mice include diffuse and moderate to severe mesangial matrix expansion with mesangial cell proliferation, segmental sclerosis, nodular mesangial lesions, and decreased podocyte numbers, 54,55 and these changes are more severe than in KK mice. Additionally, oxidative stress and inflammation have been observed in the kidneys of KK-Ay mice, 56,54 and this strongly contributes to the pathogenesis of kidney injury. However, STZ-induced diabetic KK mice and KK-Ay mice exhibit no tubulointerstitial fibrosis.…”

Section: Kk and Kk-ay Micementioning

confidence: 99%

Rodent models of diabetic nephropathy: their utility and limitations

Kitada¹,

Ogura²,

Koya³

2016

IJNRD

200

151

View full text Add to dashboard Cite

Diabetic nephropathy is the most common cause of end-stage renal disease. Therefore, novel therapies for the suppression of diabetic nephropathy must be developed. Rodent models are useful for elucidating the pathogenesis of diseases and testing novel therapies, and many type 1 and type 2 diabetic rodent models have been established for the study of diabetes and diabetic complications. Streptozotocin (STZ)-induced diabetic animals are widely used as a model of type 1 diabetes. Akita diabetic mice that have an Ins2+/C96Y mutation and OVE26 mice that overexpress calmodulin in pancreatic β-cells serve as a genetic model of type 1 diabetes. In addition, db/db mice, KK-Ay mice, Zucker diabetic fatty rats, Wistar fatty rats, Otsuka Long-Evans Tokushima Fatty rats and Goto-Kakizaki rats serve as rodent models of type 2 diabetes. An animal model of diabetic nephropathy should exhibit progressive albuminuria and a decrease in renal function, as well as the characteristic histological changes in the glomeruli and the tubulointerstitial lesions that are observed in cases of human diabetic nephropathy. A rodent model that strongly exhibits all these features of human diabetic nephropathy has not yet been developed. However, the currently available rodent models of diabetes can be useful in the study of diabetic nephropathy by increasing our understanding of the features of each diabetic rodent model. Furthermore, the genetic background and strain of each mouse model result in differences in susceptibility to diabetic nephropathy with albuminuria and the development of glomerular and tubulointerstitial lesions. Therefore, the validation of an animal model reproducing human diabetic nephropathy will significantly facilitate our understanding of the underlying genetic mechanisms that contribute to the development of diabetic nephropathy. In this review, we focus on rodent models of diabetes and discuss the utility and limitations of these models for the study of diabetic nephropathy.

show abstract

Section: Kk and Kk-ay Micementioning

confidence: 99%

Rodent models of diabetic nephropathy: their utility and limitations

Kitada¹,

Ogura²,

Koya³

2016

IJNRD

200

151

View full text Add to dashboard Cite

show abstract

“…In fact, basic and clinical data suggest that these least diabetogenic statins, especially pitavastatin, may even exhibit a positive effect on glucose metabolism. [35][36][37][38][39][40][41][42][43] Intricately layered with our full understanding of why and how statins negatively or positively impact glycemic health is an array of factors including patient characteristics and integrative control mechanisms of cholesterol regulation. It is also now recognized that high-potency, high-dose, and long-treatment durations add to the diabetogenicity of statins, however, pitavastatin, a fully synthetic and high-potency statin, 44 is a notable exception that displays many cellular cholesterol homeostatic antidiabetic attributes, which will be reviewed below.…”

Section: Challenges Opportunities and Lessons From Statin Therapymentioning

confidence: 99%

New Aspects of Cellular Cholesterol Regulation on Blood Glucose Control—Review and Perspective on the Impact of Statin Medications on Metabolic Health

Grice

Elmendorf

2017

US Endocrinology

View full text Add to dashboard Cite

Cholesterol is an essential component of cell membranes, and during the past several years, diabetes researchers have found that membrane cholesterol levels in adipocytes, skeletal muscle fibers and pancreatic beta cells influence insulin action and insulin secretion. Consequently, it is thought that dysregulated cell cholesterol homeostasis could represent a determinant of type 2 diabetes (T2D). Recent clinical findings compellingly add to this notion by finding increased T2D susceptibility in individuals with alterations in a variety of cholesterol metabolism genes. While it remains imperfectly understood how statins influence glucose metabolism, the fact that they display an influence on blood glucose levels and diabetes susceptibility seems to intensify the emerging importance of understanding cellular cholesterol in glucose metabolism. Taking this into account, this review first presents cell system and animal model findings that demonstrate the negative impact of cellular cholesterol accumulation or diminution on insulin action and insulin secretion. With this framework, a description of how changes in cholesterol metabolism genes are associated with T2D susceptibility will be presented. In addition, the connection between statins and T2D risk will be reviewed with expanded information on pitavastatin, a newer statin medication that displays actions favoring metabolic health.

show abstract

“…KK-A y /Ta mice spontaneously exhibit type 2 diabetes mellitus signs, including hyperglycemia, glucose intolerance, hyperinsulinemia, obesity, and microalbuminuria. The mice also develop renal lesions that show diffuse hyperplasi of the mesangial area with mesangial cell (MC) proliferation, segmental sclerosis, overexpression of TGF-␤1, and accumulation of advanced glycation end products and ROS products (22,27,39).…”

mentioning

confidence: 99%

Attenuating effect of angiotensin-(1–7) on angiotensin II-mediated NAD(P)H oxidase activation in type 2 diabetic nephropathy of KK-A^y/Ta mice

Moon

Tanimoto

Gohda

et al. 2011

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

-7) is associated with vasodilation and nitric oxide synthase stimulation. However, the role of ANG-(1-7) in type 2 diabetes mellitus is unknown. In this study, we examined the hypothesis that ANG-(1-7) attenuates ANG II-induced reactive oxygen species stress (ROS)-mediated injury in type 2 diabetic nephropathy of KK-A y /Ta mice. KK-A y /Ta mice were divided into four groups: 1) a control group; 2) ANG II infusion group; 3) ANG IIϩANG-(1-7) coinfusion group; and 4) ANG IIϩANG-(1-7)ϩD-Ala 7 -ANG-(1-7) (A779) coinfusion group. In addition, primary mesangial cells were cultured and then stimulated with 25 mM glucose with or without ANG II, ANG-(1-7), and A779. The ANG IIϩANG-(1-7) coinfusion group showed a lower urinary albumin/creatinine ratio increase than the ANG II group. ANG-(1-7) attenuated ANG II-mediated NAD(P)H oxidase activation and ROS production in diabetic glomeruli and mesangial cells. ANG II-induced NF-B and MAPK signaling activation was also attenuated by ANG-(1-7) in the mesangial cells. These findings were related to improved mesangial expansion and to fibronectin and transforming growth factor-␤1 production in response to ANG II and suggest that ANG-(1-7) may attenuate ANG II-stimulated ROSmediated injury in type 2 diabetic nephropathy. The ACE2-ANG-(1-7)-Mas receptor axis should be investigated as a novel target for treatment of type 2 diabetic nephropathy.THE RECENT DISCOVERY OF THE renal renin-angiotensin system (RAS) (41), angiotensin-converting enzyme-related carboxypeptidase (ACE2), and ANG-(1-7) has changed the way the RAS is viewed. ANG-(1-7) is present in kidneys at concentrations comparable to ANG II and is associated with vasodilation, modulation of sodium and water transport, and stimulation of nitric oxide synthase (NOS) (7,9,24,34). The effect of ANG-(1-7) on diabetes is still not clear. In a recent study using the streptozotocin-induced diabetic rat model, ANG-(1-7) infusion prevented diabetes-induced abnormal vascular responses to norepinephrine, endothelin-1, and ANG II in the perfused mesenteric bed and renal arteries. This study also reported decreased urinary albumin excretion in response to ANG-(1-7) (6, 7, 13). Another study in the same streptozotocin-induced diabetic rat model showed that chronic injection of ANG-(1-7) accelerated diabetic renal injury (36). In db/db mice, glomerular expression of ACE2 was increased, and ACE2 inhibitor use showed increased glomerular staining for fibronectin and an extracellular matrix protein (42). However, there have been no studies on the direct effect of ANG-(1-7) on ANG II-induced diabetic glomerular changes.

show abstract

Effect of pitavastatin on type 2 diabetes mellitus nephropathy in KK-Ay/Ta mice

Cited by 29 publications

References 31 publications

Rodent models of diabetic nephropathy: their utility and limitations

Rodent models of diabetic nephropathy: their utility and limitations

New Aspects of Cellular Cholesterol Regulation on Blood Glucose Control—Review and Perspective on the Impact of Statin Medications on Metabolic Health

Attenuating effect of angiotensin-(1–7) on angiotensin II-mediated NAD(P)H oxidase activation in type 2 diabetic nephropathy of KK-A^y/Ta mice

Contact Info

Product

Resources

About

Effect of pitavastatin on type 2 diabetes mellitus nephropathy in KK-Ay/Ta mice

Cited by 29 publications

References 31 publications

Rodent models of diabetic nephropathy: their utility and limitations

Rodent models of diabetic nephropathy: their utility and limitations

New Aspects of Cellular Cholesterol Regulation on Blood Glucose Control—Review and Perspective on the Impact of Statin Medications on Metabolic Health

Attenuating effect of angiotensin-(1–7) on angiotensin II-mediated NAD(P)H oxidase activation in type 2 diabetic nephropathy of KK-Ay/Ta mice

Contact Info

Product

Resources

About

Attenuating effect of angiotensin-(1–7) on angiotensin II-mediated NAD(P)H oxidase activation in type 2 diabetic nephropathy of KK-A^y/Ta mice