Mechanism for exercise-mediated prevention against muscle wasting on extensor digitorum longus muscle in Spontaneously Diabetic Torii fatty rats.

We previously reported the significant increase in limb muscle strength and cross-sectional area of the type IIb muscle fibers in the extensor digitorum longus (EDL) muscle in a type 2 diabetic animal model, with Spontaneously Diabetic Torii (SDT) fatty rats (n = 6) undergoing regular treadmill exercise from 8 to 16 weeks of age compared with sedentary SDT fatty rats (n = 6). This study investigated the mechanism by which exercise training prevented skeletal muscle wasting in the EDL muscle of the SDT fatty rats. The endurance exercise for 8 weeks downregulated the expression of muscle RING-finger protein-1 (an E3 ubiquitin ligase) and upregulated the expression of CD31, insulin receptor substrate-2, and phosphorylated endothelial nitric oxide synthase in the EDL muscle of 16-week-old SDT fatty rats.

Angiotensin II type 1a receptor deficiency alleviates muscle atrophy after denervation.

The study aim was to determine if suppressed activation of angiotensin II type 1 receptor (AT1) prevents severe muscle atrophy after denervation. The sciatic nerves in right and left inferior limbs were cut in AT1a knockout homo (AT1a) male mice and wild-type (AT1a) male mice. Muscle weight and cross-sectional areas of type IIb muscle fibers in gastrocnemius muscle decreased at 7 and 21 days postdenervation in both AT1a mice and AT1a mice, and the reduction was significantly attenuated in the denervated muscles of AT1a mice compared to the AT1a mice.

Glucagon-like peptide-1 receptor agonist, liraglutide, attenuated retinal thickening in spontaneously diabetic Torii fatty rats.

Background: This study aims to investigate the effect of the glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) liraglutide on retinal pathological findings as compared with insulin and hydralazine using an animal model of type 2 diabetes with obesity, hypertension, and hyperlipidemia.

Methods: Male spontaneously diabetic Torii (SDT) fatty rats at 8 weeks of age were randomly assigned to three groups: the liraglutide group (SDT-lira, n = 6) received a subcutaneous injection of liraglutide from the age of 8 to 16 weeks, the SDT-ins-hyd group (n = 6) was provided both insulin against hyperglycemia and hydralazine against hypertension to match levels of both blood glucose and blood pressure to those of the liraglutide group, and the control group of SDT fatty rats (SDT-vehicle, n = 7) and a nondiabetic control group of Sprague-Dawley rats (SD, n = 7) were injected with vehicle only. Both eyeballs of all groups were collected at the age of 16 weeks.

Endurance Exercise Training-Attenuated Diabetic Kidney Disease with Muscle Weakness in Spontaneously Diabetic Torii Fatty Rats.

Background: The aim of this study was to evaluate protective effects of endurance exercise training against diabetic kidney disease (DKD) with muscle weakness by using male spontaneously diabetic Torii (SDT) fatty rats as type 2 diabetic animal models with obesity, hypertension, and hyperlipidemia.

Methods: Eight-week-old SDT fatty rats (n = 12) and Sprague-Dawley (SD) rats (n = 10) were randomly divided into exercise (Ex; SDT-Ex: n = 6, SD-Ex: n = 5) and sedentary groups (SDT-Cont: n = 6, SD-Cont: n = 5), respectively. Each group underwent regular treadmill exercise 4 times a week from ages 8-16 weeks.

Effect of GLP-1 receptor agonist, liraglutide, on muscle in spontaneously diabetic torii fatty rats.

This study investigated the effect of liraglutide, a glucagon-like peptide-1 receptor agonist, on skeletal muscles in rats with type 2 diabetes. Male SDT fatty rats (8-week-old) were provided liraglutide, or insulin-hydralazine for 8 weeks; control SDT fatty rats and SD rats were administered a vehicle. At 16 weeks of age, muscle strength of limbs was significantly lower in all SDT fatty rats compared to SD rats.

Angiotensin II type 1a receptor loss ameliorates chronic tubulointerstitial damage after renal ischemia reperfusion.

We investigate whether suppressing the activation of the angiotensin II type 1a receptor (AT1a) can ameliorate severe chronic tubulointerstitial damage (TID) after renal ischemia reperfusion (IR) using AT1a knockout homozygous (AT1a) male mice. To induce severe chronic TID after renal IR, unilateral renal ischemia was performed via clamping of the right renal pedicle in both AT1a and wild-type (AT1a) mice for 45 min. While marked renal atrophy and severe TID at 70 days postischemia was induced in the AT1a mice, such a development was not provoked in the AT1a mice.

Renoprotective effect of GLP-1 receptor agonist, liraglutide, in early-phase diabetic kidney disease in spontaneously diabetic Torii fatty rats.

Background: The aim of this study is to investigate the renoprotective effect of the GLP-1 receptor agonist, liraglutide, in early-phase diabetic kidney disease (DKD) using an animal model of type 2 diabetes with several metabolic disorders.

Methods: Male 8-week-old spontaneously diabetic Torii (SDT) fatty rats (n = 19) were randomly assigned to three groups. The liraglutide group (n = 6) was injected subcutaneously with liraglutide.

Relationship between Urinary Liver-Type Fatty Acid-Binding Protein (L-FABP) and Sarcopenia in Spontaneously Diabetic Torii Fatty Rats.

Background: Type 2 diabetes (T2D) is a known risk factor for diabetic kidney disease (DKD) and sarcopenia in older patients. Because there may be an interaction between DKD and sarcopenia, the aim of the present study is to investigate the relationship between urinary levels of liver-type fatty acid-binding protein (L-FABP) and sarcopenia using a novel rat model of T2D.

Methods: Male spontaneously diabetic Torii (SDT) fatty rats ( = 5) at 16 weeks of age were used as an animal model of T2D.

The Possibility of Urinary Liver-Type Fatty Acid-Binding Protein as a Biomarker of Renal Hypoxia in Spontaneously Diabetic Torii Fatty Rats.

Background: Renal hypoxia is an aggravating factor for tubulointerstitial damage, which is strongly associated with renal prognosis in diabetic kidney disease (DKD). Therefore, urinary markers that can detect renal hypoxia are useful for monitoring DKD.

Objective: To determine the correlation between urinary liver-type fatty acid-binding protein (L-FABP) and renal hypoxia using a novel animal model of type 2 diabetes.

Renoprotective effects of voluntary running exercise training on aldosterone-induced renal injury in human L-FABP chromosomal transgenic mice.

Tubulointerstitial damage is a crucial therapeutic target in preventing chronic kidney disease (CKD) progression. Inappropriately activated renin-angiotensin-aldosterone system (RAAS) in the tubulointerstitial area is strongly associated with tubulointerstitial damage progression. Therefore, this study aimed to determine whether there is a beneficial effect of voluntary running exercise training on aldosterone-induced renal injury.

Urinary Level of Liver-Type Fatty Acid Binding Protein Reflects the Degree of Tubulointerstitial Damage in Polycystic Kidney Disease.

Background/aims: Polycystic kidney disease (PKD) is a common, progressive, and heritable type of kidney disease. Although certain imaging modalities are useful for the diagnosis and staging of PKD, they cannot adequately monitor the severity of interstitial inflammation and fibrosis. Therefore, the present study evaluated the urinary level of liver-type fatty acid binding protein (L-FABP) as a marker of interstitial inflammation and fibrosis in PKD.

Role of bardoxolone methyl, a nuclear factor erythroid 2-related factor 2 activator, in aldosterone- and salt-induced renal injury.

The aim of this study was to investigate the renoprotective effect of bardoxolone methyl (BM), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator with an antioxidant effect, in a salt-sensitive hypertension model induced by aldosterone (Ald) and salt. Tubulointerstitial damage with urinary liver-type fatty acid-binding protein (L-FABP) was evaluated using human L-FABP chromosomal transgenic (L-FABP) male mice. The mice in the Ald group (n=7) received systemic Ald infusions via an osmotic minipump and were given 1% NaCl water for 35 days.

Renoprotective effect of the xanthine oxidoreductase inhibitor Topiroxostat under decreased angiotensin II type 1 receptor expression.

The aim of this study was to confirm the renoprotective effect of xanthine oxidoreductase (XOR) inhibitor, topiroxostat, compared with another XOR inhibitor, febuxostat, under decreased angiotensin II type 1 (AT1) receptor expression in the model of renal injury caused by adenine. To evaluate the degree of tubular damage using urinary liver-type fatty acid-binding protein (L-FABP) under decreased AT1 expression, we used AT1 receptor knockdown hetero and human L-FABP chromosomal transgenic (Tg) mice (AT1L-FABP). Male AT1L-FABP mice were divided into two groups: the adenine diet group (n = 40) was given a diet containing only 0.

Utility of urinary tubular markers for monitoring chronic tubulointerstitial injury after ischemia-reperfusion.

Aim: The aim of this study was to elucidate whether urinary tubular markers during the chronic phase of acute kidney injury (AKI) are associated with chronic tubulointerstitial damage.

Methods: Male human L-type fatty acid binding protein (L-FABP) chromosomal transgenic (Tg) mice underwent ischaemic reperfusion (I/R) injury via renal pedicle clamping for either 10 min or 20 min. Contralateral nephrectomy was performed at the time of tissue reperfusion.

Role of angiotensin II type 1a receptor in renal injury induced by deoxycorticosterone acetate-salt hypertension.

The aim of this study was to investigate the in vivo role of angiotensin II type 1a (AT1a) receptor in renal damage as a result of hypertension by using transgenic mice with AT1a receptor gene disruption. Transgenic mice that express human liver-type fatty acid binding protein (L-FABP) with or without disruption of the AT1a receptor gene (L-FABP AT1a, and L-FABP AT1a, respectively) were used with urinary L-FABP as an indicator of tubulointerstitial damage. Those female mice were administered subcutaneously deoxycorticosterone acetate (DOCA)-salt tablets plus drinking water that contained 1% saline for 28 d after uninephrectomy.

Renoprotective effect of the xanthine oxidoreductase inhibitor topiroxostat on adenine-induced renal injury.

The aim of the present study was to reveal the effect of a xanthine oxidoreductase (XOR) inhibitor, topiroxostat (Top), compared with another inhibitor, febuxostat (Feb), in an adenine-induced renal injury model. We used human liver-type fatty acid-binding protein (L-FABP) chromosomal transgenic mice, and urinary L-FABP, a biomarker of tubulointerstitial damage, was used to evaluate tubulointerstitial damage. Male transgenic mice (n = 24) were fed a 0.

Increase in urinary markers during the acute phase reflects the degree of chronic tubulointerstitial injury after ischemia-reperfusion renal injury.

Context: Acute kidney injury (AKI) could lead to progressive chronic kidney disease (CKD).

Objectives: To demonstrate that urinary markers in AKI are associated with the degree of persistent renal injury.

Material And Methods: Human L-FABP chromosomal transgenic (T) mice were subjected to ischemia-reperfusion (I/R) clamping renal pedicle for 20 min or 30 min.

Clinical utility of urinary liver-type fatty acid binding protein measured by latex-enhanced turbidimetric immunoassay in chronic kidney disease.

Background: Urinary liver-type fatty acid binding protein (L-FABP) measured by enzyme-linked immunosorbent assay method (ELISA) was approved as a clinical biomarker of tubular damage by the Japanese Ministry of Health, Labor and Welfare (MHLW) in 2011. We evaluated a new latex-enhanced immunoturbidimetric assay (LTIA) to evaluate the clinical utility of urinary L-FABP measured by LTIA versus an ELISA assay.

Methods: LTIA with anti-human L-FABP mouse monoclonal antibodies was performed using an automated clinical chemistry analyzer.

Human liver-type fatty acid-binding protein protects against tubulointerstitial injury in aldosterone-induced renal injury.

To demonstrate the renoprotective function of human liver-type fatty acid-binding protein (hL-FABP) expressed in proximal tubules in aldosterone (Aldo)-induced renal injury, hL-FABP chromosomal transgenic (Tg) and wild-type (WT) mice received systemic Aldo infusions (Tg-Aldo and WT-Aldo, respectively) were given 1% NaCl water for 28 days. In this model, elevation of systolic blood pressure, monocyte chemoattractant protein-1 expression, macrophage infiltration in the interstitium, tubulointerstitial damage, and depositions of type I and III collagens were observed. Elevation of systolic blood pressure did not differ in WT-Aldo vs.

Renoprotective effect of renal liver-type fatty acid binding protein and angiotensin II type 1a receptor loss in renal injury caused by RAS activation.

The aim of this study was to assess the renoprotective effect of renal human liver-type fatty acid binding protein (hL-FABP) and angiotensin II (ANG II) type 1A receptor (AT1a) loss in renal injury caused by renin-angiotensin system (RAS) activation. We established hL-FABP chromosomal transgenic mice (L-FABP(+/-)AT1a(+/+)), crossed the L-FABP(+/-)AT1a(+/+) with AT1a knockdown homo mice (L-FABP(-/-)AT1a(-/-)), and generated L-FABP(+/-)AT1a hetero mice (L-FABP(+/-)AT1a(+/-)). After the back-cross of these cubs, L-FABP(+/-)AT1a(-/-) were obtained.

Urinary liver type fatty acid binding protein in diabetic nephropathy.

Deterioration of diabetic nephropathy (DN) is largely determined by the degree of tubulointerstitial changes rather than the extent of histological changes in the glomeruli. Therefore, a tubular marker that accurately reflects tubulointerstitial damage may be an excellent biomarker for early detection or prediction of DN. Liver-type fatty-acid binding protein (L-FABP) is a 14 kDa small molecule that is expressed in the cytoplasm of human proximal tubules.

Renal liver-type fatty acid binding protein attenuates angiotensin II-induced renal injury.

To investigate the role of human liver-type fatty acid binding protein (hL-FABP) in angiotensin (Ang) II-induced renal injury, Ang II was infused systemically into hL-FABP chromosomal transgenic (Tg) and wild-type (WT) mice (Tg-Ang II and WT-Ang II) for 28 days. Control mice were injected with saline only (Tg-control and WT-control). hL-FABP was expressed in proximal tubules of Tg mice.

Urinary excretion of liver type fatty acid binding protein accurately reflects the degree of tubulointerstitial damage.

To investigate the relationship between liver-type fatty acid-binding protein (L-FABP), a biomarker of chronic kidney disease, in the kidney and the degree of tubulointerstitial damage, folic acid (FA)-induced nephropathy was studied in a mouse model system. As renal L-FABP is not expressed in wild-type mice, human L-FABP (hL-FABP) transgenic mice were used in this study. hL-FABP is expressed in the renal proximal tubules of the transgenic mice that were injected intraperitoneally with FA in NaHCO3 (the FA group) or only NaHCO3 (the control group) and oral saline solution daily during the experimental period.