ライフサイエンスコーパス: ZDF rat

1 ZDF rats at 12 weeks of age showed a significant reducti

2 ZDF rats compared with ZCL rats have lower hepatic GK ac

3 ZDF rats were treated at various doses with an adenoviru

4 ZDF rats with global deletion of CB1R are protected from

5 Six lean and ZDF rats underwent small-animal PET at the age of 14 wk

6 vements in glucose tolerance in DIO mice and ZDF rats were observed after 2 weeks of q.d. dosing.

7 inistration of DM199 in obese db/db mice and ZDF rats, showed an acute, dose-dependent improvement in

8 nas obtained from the same groups of STZ and ZDF rats was significantly reduced at all time points ex

9 leptin by approximately 20 ng/ml in VMHL and ZDF rats but had no effect on their food intake, body we

10 hyperglycemia was reduced in both Wistar and ZDF rats after pioglitazone administration.

11 nsulin resistant and hyperinsulinemic ZF and ZDF rats, relative to the ZLC rat; 2) at 12 weeks of age

12 nesis and apoptosis is evident in the ZF and ZDF rats.

13 a control for mGPD, was normal in the ZL and ZDF rats.

14 pe 1 skeletal muscle of both lean Zucker and ZDF rats.

15 Because ZDF rats are homozygous for a mutation in their leptin r

16 n secretion, which was negligible in control ZDF rat islets, was improved in UCP-2-overexpressing isl

17 beta in a rat beta cell line and in cultured ZDF rat, mouse, and human islets.

18 glucose levels would prevent these defects, ZDF rats were treated with troglitazone beginning at 6 w

19 NAD did not develop in diabetic ZDF rat sympathetic ganglia and ileal mesenteric nerves

20 are high (>1 mM) in prediabetic and diabetic ZDF rats; therefore, we cultured prediabetic islets in 1

21 ce and insulin secretory defects in diabetic ZDF rats is inadequate.

22 red the UCP-2 gene to the islets of diabetic ZDF rats and lean (+/+) ZDF control rats.

23 ecause the fat content of islets of diabetic ZDF rats remains high unless they are treated with lepti

24 Treatment of diabetic ZDF rats with losartan, an angiotensin II receptor-1 (Ag

25 ive UCP-2-underexpressing islets of diabetic ZDF rats, we transferred the UCP-2 gene to the islets of

26 Fa/fa ZDF rats had higher IMCL contents than controls througho

27 Fa/fa ZDF rats were studied at 3 different ages corresponding

28 at of wild-type (+/+) and homozygous (fa/fa) ZDF rats.

29 beta-actin mRNA ratio in heterozygous (fa/+) ZDF rats with that of wild-type (+/+) and homozygous (fa

30 Zucker diabetic fat (ZDF) rats with the metabolic syndrome and hyperlipidemia

31 PD is abnormal in the Zucker diabetic fatty (ZDF) rat (ZDF/Gmi-fa/fa), an animal model of NIDDM in wh

32 duced model in type-2 Zucker diabetic fatty (ZDF) rat and normoglycemic littermates, we investigated

33 from the prediabetic Zucker diabetic fatty (ZDF) rat between 5-6 weeks and 12 weeks of age (after th

34 The Zucker diabetic fatty (ZDF) rat is a model of type 2 diabetes and, like the hum

35 mozygous mutant (-/-) Zucker diabetic fatty (ZDF) rat is related more to chronic hyperglycemia or to

36 crocirculation of the Zucker diabetic fatty (ZDF) rat was quantified by intravital microscopy.

37 The Zucker Diabetic Fatty (ZDF) rat, an animal model of type 2 diabetes, also devel

38 vivo, we studied the Zucker diabetic fatty (ZDF) rat, an animal model of type 2 diabetes.

39 diabetes, namely the Zucker diabetic fatty (ZDF) rat, and validated PET measurements of glucose upta

40 on of diabetes in the Zucker diabetic fatty (ZDF) rat, beta-cell mass and replication rates were dete

41 ic obesity, the fa/fa Zucker diabetic fatty (ZDF) rat, the mechanisms involved in the most common com

42 togenic mutation, the Zucker diabetic fatty (ZDF) rat, we cultured islets from 6-week-old obese (fa/f

43 bese hyperinsulinemic Zucker diabetic fatty (ZDF) rats 45 min after a single oral dose of pioglitazon

44 uced hyperglycemia in Zucker diabetic fatty (ZDF) rats after single oral doses ranging from 0.1 to 1.

45 e and triglyceride in Zucker diabetic fatty (ZDF) rats and db/db mice, decreased the expression of th

46 ic and nonprediabetic Zucker diabetic fatty (ZDF) rats and of lean Wistar and lean ZDF rats.

47 Ten-week-old Zucker diabetic fatty (ZDF) rats at an early stage of diabetes embody metabolic

48 skeletal muscle from Zucker diabetic fatty (ZDF) rats compared with lean controls and determined the

49 esistance arteries in Zucker diabetic fatty (ZDF) rats compared with lean Zucker (LZ) rats.

50 Zucker diabetic fatty (ZDF) rats develop type 2 diabetic nephropathy with album

51 Like obese humans, Zucker diabetic fatty (ZDF) rats exhibit early beta cell compensation for insul

52 process replicated in Zucker Diabetic Fatty (ZDF) rats in which beta-cell loss has been linked to can

53 ed (SL) controls, and Zucker Diabetic Fatty (ZDF) rats in which the leptin receptor is mutated.

54 output in prediabetic Zucker diabetic fatty (ZDF) rats is mediated by NO.

55 sion in beta cells of Zucker diabetic fatty (ZDF) rats is profoundly reduced at the onset of beta-cel

56 nization of islets of Zucker diabetic fatty (ZDF) rats is the proximal cause of their inability to co

57 29 or troglitazone to Zucker diabetic fatty (ZDF) rats resulted in dose-dependent decreases in daily

58 islets of obese fa/fa Zucker Diabetic Fatty (ZDF) rats results from overproduction of ceramide, an in

59 rom pre-diabetic male Zucker diabetic fatty (ZDF) rats showed increased expression of hypoxia-related

60 tic genes from female Zucker diabetic fatty (ZDF) rats treated with the FXR agonist GW4064, we have i

61 nd fatty (fa/fa), and Zucker diabetic fatty (ZDF) rats were studied.

62 amined in 20-week-old Zucker diabetic fatty (ZDF) rats whether restoration of hepatic glucokinase (GK

63 ow that treating male Zucker diabetic fatty (ZDF) rats with E2 suppressed synthesis and accumulation

64 er early treatment of Zucker diabetic fatty (ZDF) rats with ebselen, an oral GPx mimetic, will preven

65 In obese Zucker diabetic fatty (ZDF) rats with mutant leptin receptors, pancreatic islet

66 in lipid dynamics in Zucker diabetic fatty (ZDF) rats, in response to 7 days of treatment with eithe

67 ic rings from BBd and Zucker diabetic fatty (ZDF) rats, models of human type I and type II diabetes,

68 from Lean control and Zucker Diabetic Fatty (ZDF) rats, using single-channel recording techniques.

69 in hyperglycemic male Zucker diabetic fatty (ZDF) rats, with an ED(50) for glucose normalization of 3

70 n Norway (FBN) and in Zucker Diabetic Fatty (ZDF) rats.

71 receptor agonist, in Zucker diabetic fatty (ZDF) rats.

72 e adipogenic NIDDM of Zucker diabetic fatty (ZDF) rats.

73 of type 2 diabetes in Zucker diabetic fatty (ZDF) rats.

74 amined in 14-week-old Zucker diabetic fatty (ZDF) rats.

75 ue-Dawley [S-D] rats, Zucker diabetic fatty [ZDF] rats, and rats expressing human islet amyloid polyp

76 impaired glucose homeostasis in high-fat fed ZDF rats.

77 In vivo administration of GW4064 to female ZDF rats promoted a dose-dependent and >6-fold increase

78 soyasaponin-1 (DHS-1) was lost in cells from ZDF rats.

79 Islets from ZDF rats failed to increase insulin secretion in respons

80 Isolated islets from ZDF rats were completely resistant to the lipopenic acti

81 0.05, respectively) in skeletal muscle from ZDF rats compared with lean controls.

82 GLUT4 levels in skeletal muscle from ZDF rats were similar to those in lean control animals.

83 ts of 6-week-old heterozygous and homozygous ZDF rats lack the capacity for FFA-induced enhancement o

84 Three weeks prior to imaging, ZDF rats were randomized into a no-restriction (ZDF-ND)

85 ey feeding behavior and metabolic centers in ZDF rat brain or directly enhance glucose-stimulated ins

86 In ZDF rats, hyperphagia leads to hyperinsulinemia, which u

87 Alteration of hepatic GK activity in ZDF rats has profound effects on plasma glucose and hepa

88 for NF vessels, but this was not the case in ZDF rats.

89 er oral or intravenous glucose challenges in ZDF rats and db/db mice, without causing hypoglycemia or

90 We found that BK channels in ZDF rats have impaired Ca(2+) sensitivity, including an

91 % to 32%) but was significantly decreased in ZDF rats after 2 to 5 months of diabetes (-9% to -16%).

92 erglycemia resulting from type 2 diabetes in ZDF rats is associated with loss of insulin and PDX-1 mR

93 the proximate cause of lipotoxic diabetes in ZDF rats.

94 Endothelium-mediated dilation in ZDF rats, which was lower than in LZ rats, was further d

95 When dosed in ZDF rats, 25 showed both a robust pharmacodynamic effect

96 lexibility and glucose flux were examined in ZDF rats during fasting and near-normal postprandial ins

97 also attenuated urinary albumin excretion in ZDF rats.

98 ose-dependently reduced glucose excursion in ZDF rats.

99 in BK channel beta(1)-subunit expression in ZDF rats, compared with that of Lean rats.

100 nd the impaired beta-cell response to FFA in ZDF rats.

101 d oxidation and postprandial glucose flux in ZDF rats.

102 e parameters of peripheral nerve function in ZDF rats.

103 ed with impaired regulation of GK by GKRP in ZDF rats.

104 However, in ZDF rats and db/db mice, there was profound increase in

105 d glucose levels were significantly lower in ZDF rats during a drug wash-out period.

106 LUT-4 was significantly (P = 0.004) lower in ZDF rats.

107 ements of myocardial substrate metabolism in ZDF rats using small-animal PET are consistent with the

108 MGUp in ZDF rats at both week 14 (W14) and W19 (P < 0.006) was s

109 The level of adipose ob mRNA in ZDF rats was 3-fold greater than that detected in the Zu

110 Metanx on diabetic peripheral neuropathy in ZDF rats, a model of type 2 diabetes.

111 ion of normoglycemia and normoinsulinemia in ZDF rats with rosiglitazone (30 micromol/kg) normalized

112 ression in islets of normal rats, but not in ZDF rats, in which PPARalpha is very low.

113 was slightly increased in Wistar but not in ZDF rats.

114 ance of 3-nitrotyrosine-modified proteins in ZDF rats.

115 ndothelial cells is progressively rampant in ZDF rats and is associated with the signs of severe vasc

116 for HF-dependent remodeling, was reduced in ZDF rats compared with LZ rats and restored by ALT-711.

117 gen species reduction restored relaxation in ZDF rats but not in LZ or ALT-711-treated rats.

118 f nonesterified free fatty acids was seen in ZDF rats but not in db/db mice.

119 d nuclear magnetic resonance spectroscopy in ZDF rats during early and advanced diabetes.

120 glucose in an oral glucose tolerance test in ZDF rats.

121 These results show that in ZDF rats, treatment with a synthetic insulin-receptor-ac

122 d at the mechanistic level, removal of VF in ZDF rats prevented the progressive decrease in insulin a

123 Sub-acute dosing for a week in ZDF rats improved glucose utilization, with a concomitan

124 fatty (ZDF) rats and of lean Wistar and lean ZDF rats.

125 esity and apparently normal islets from lean ZDF rats (fa/+) in 0, 1, or 2 mM FFA.

126 increased only slightly in islets from lean ZDF rats (not significant) and declined in islets from o

127 ated islets of ZDF rats or in islets of lean ZDF rats.

128 islets but not in islets from obese or lean ZDF rats.

129 despite a similar impact on glycemia in male ZDF rats.

130 us administration of NRTN to 8-week-old male ZDF rats prevented the development of hyperglycemia and

131 ncreased approximately twofold in young male ZDF rats by both morphometric analysis and quantifying m

132 gnificant) and declined in islets from obese ZDF rats (p < 0.05).

133 in the range of those found in the blood of ZDF rats increased albumin permeability in nondiabetic Z

134 the culture medium reduced the TG content of ZDF rats by 52%; this was reflected by decreased esterif

135 ramyocardial lipid overload in the hearts of ZDF rats was associated with contractile dysfunction and

136 lioration of beta cell function in islets of ZDF rats might be associated with a reduction in their e

137 rise in either the precompensated islets of ZDF rats or in islets of lean ZDF rats.

138 tin and is low in leptin-resistant islets of ZDF rats.

139 We conclude that lipoapoptosis of ZDF rats is mediated by enhanced ceramide synthesis from

140 sation of albumin in the microcirculation of ZDF rats was significantly increased when compared with

141 Chronic ebselen treatment of ZDF rats restored renal tissue levels of glutathione and

142 Treatment of ZDF rats with different doses of AdvCMV-GKL, which resto

143 Islets from 15-week-old ZDF rats did not induce migration; rather, they caused a

144 nts were performed in prediabetic 6-week-old ZDF rats in comparison with 12-week-old overtly hypergly

145 Islets from 7-week-old ZDF rats showed a fivefold increase in migration score c

146 Islets from 7- and 12-week-old ZDF rats showed an approximate three- and twofold increa

147 ctron microscopy of normoglycemic 7-week-old ZDF rats showed thickened endothelial cells with loss of

148 Treating 10-week-old ZDF rats with sustained hyperglycemia with liraglutide r

149 8% of normal in islets of 6- and 12-week-old ZDF rats, respectively (P < 0.001 by analysis of varianc

150 f normal in the islets of 6- and 12-week-old ZDF rats, respectively (P < 0.001).

151 As glycemia increased in 12- and 16-week-old ZDF rats, we observed decrements in glucose-induced insu

152 red with age-matched ZLC rats and 6-week-old ZDF rats.

153 Given orally in db/db mice or ZDF rats, 46a,b showed a significant glucose-lowering ef

154 al islets and in islets of obese prediabetic ZDF rats; in the latter, this correlated with improvemen

155 e or aminoguanidine treatment of prediabetic ZDF rats prevented the iNOS expression in islets and dec

156 ta-cell mass in 5- to 7-week-old prediabetic ZDF rats (4.3 +/- 0.06 mg) was similar to age-matched in

157 ly prevented in vivo by treating prediabetic ZDF rats with L-cycloserine for 2 weeks.

158 Whereas prediabetic ZDF rats had a fourfold elevation in islet fat, in VMHL

159 Troglitazone prevented ZDF rats from becoming hyperglycemic and preserved gluco

160 specific in vivo knockdown of Irf5 protected ZDF rats from beta-cell loss and hyperglycemia.

161 1 skeletal muscle from the insulin-resistant ZDF rats but not from insulin-sensitive lean Zucker rats

162 Since ZDF rats are euglycemic at 6 weeks of age and ZL animals

163 In our study, ZDF rats maintained for 6 to 7 months in a severely diab

164 These findings suggest that ZDF rats develop a progressive nephropathy with glomerul

165 re made between the activity observed in the ZDF rat and that seen in the ZDF lean control (ZLC) rat

166 s failure of beta-cell mass expansion in the ZDF rat does not appear to be from a reduction in the ra

167 These data suggest that in the ZDF rat model of type 2 diabetes, an inability of the is

168 nd chylomicrons (CM) was investigated in the ZDF rat model of type 2 diabetes, in order to define the

169 Accordingly, we can conclude that in the ZDF rat model, type 2 diabetes develops in the absence o

170 represent the primary genetic defect in the ZDF rat.

171 This study demonstrates that the ZDF rat carries a genetic defect in beta-cell transcript

172 The ZDF rats were treated for 6 weeks with either bezafibrat

173 ime points) was significantly greater in the ZDF rats (0.88 +/- 0.1%) compared with the ZF and ZLC ra

174 after diabetes onset), beta-cell mass in the ZDF rats (8.1 +/- 1.7 mg) was significantly lower than t

175 However, higher glucose plasma levels in the ZDF rats resulted in higher myocardial glucose utilizati

176 ificantly in db/db mice but increased in the ZDF rats.

177 doptive transfer of CB1R(-/-) bone marrow to ZDF rats also prevents beta-cell loss and hyperglycemia

178 AGEs were reduced in ALT-711-treated ZDF rats compared with ZDF rats.

179 sulin staining compared with vehicle-treated ZDF rats.

180 d blood glucose, compared with the untreated ZDF rats.

181 ed in ALT-711-treated ZDF rats compared with ZDF rats.

182 At 22 wk, ZDF rats developed focal and segmental sclerosis, protei

183 At 8 wk, ZDF rats showed hyperglycemia, no proteinuria or nephrop

184 0.62 +/- 0.07%, respectively, P < 0.05), yet ZDF rats have a lower beta-cell mass than the ZF rats de