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Pathophysiological characteristics of diabetic ocular complications in spontaneously diabetic torii rat.

Sasase T - J Ophthalmol (2010)

Bottom Line: The Spontaneously Diabetic Torii (SDT) rat, a nonobese type 2 diabetes model, develops severe diabetic retinopathy as result of chronic severe hyperglycemia.Distinctive features in SDT rat are hypermature cataract, tractional retinal detachment with fibrous proliferation, and massive hemorrhaging in the anterior chamber.These pathophysiological changes are caused by sustained hyperglycemic condition and subsequent increased expression of vascular endothelial growth factor (VEGF) in retina, iris, and ciliary body.

View Article: PubMed Central - PubMed

Affiliation: Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.

ABSTRACT
The Spontaneously Diabetic Torii (SDT) rat, a nonobese type 2 diabetes model, develops severe diabetic retinopathy as result of chronic severe hyperglycemia. Although existing diabetes animal models also develop ocular complications, severe retinal lesions frequently observed in human diabetes patients such as preretinal neovascularization or retinal detachment are not found. Distinctive features in SDT rat are hypermature cataract, tractional retinal detachment with fibrous proliferation, and massive hemorrhaging in the anterior chamber. These pathophysiological changes are caused by sustained hyperglycemic condition and subsequent increased expression of vascular endothelial growth factor (VEGF) in retina, iris, and ciliary body. Although some differences in diabetic retinopathy exist between SDT rats and humans (e.g., a low incidence of neovascular formation and poor development of nonperfused area are found in this animal), SDT rat will be a useful model in studies of the pathogenesis and treatment of diabetic retinopathy.

No MeSH data available.


Related in: MedlinePlus

Nonfasting plasma insulin and glucose levels in Spontaneously Diabetic Torii (SDT) rats and control Sprague-Dawley (SD) rats. Diminish of pancreatic β-cells evokes hypoinsulinemia (a) and subsequent severe hyperglycemia (b) in SDT rats. Plasma glucose levels sharply increase at 15–20 weeks of age and eventually reach a plateau, approximately 800 mg/dL. Each value represents mean ± S.E.M. (N = 6–8).
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fig1: Nonfasting plasma insulin and glucose levels in Spontaneously Diabetic Torii (SDT) rats and control Sprague-Dawley (SD) rats. Diminish of pancreatic β-cells evokes hypoinsulinemia (a) and subsequent severe hyperglycemia (b) in SDT rats. Plasma glucose levels sharply increase at 15–20 weeks of age and eventually reach a plateau, approximately 800 mg/dL. Each value represents mean ± S.E.M. (N = 6–8).

Mentions: Male SDT rats exhibit noticeable hyperglycemia, polyuria, and glucosuria concomitant with diminished blood insulin levels and decreased body weight by 15–20 weeks of age (Figure 1). The cumulative incidence of diabetes reaches 100% up to 40 weeks of age. In contrast, the incidence is 33% in female SDT rats [13]. Preceding the onset of diabetes, glucose intolerance with impaired insulin secretion [13, 22] and impaired lipid catabolism [23] are also observed. Genetic analysis for diabetes in SDT rats identified significant quantitative trait loci (QTL) (Gisdt1, Gisdt2, and Gisdt3) for glucose intolerance on rat chromosomes 1, 2, and X, respectively, indicating that the diabetic features in SDT rat are polygenically inherited [24]. Hyperglycemia in SDT rat is spontaneously developed, predominantly due to an insulin secretory defect resulting from pathological damage to the pancreatic islets, especially β-cells [22, 25]. Following primary microvascular events in the pancreatic islet such as congestion and hemorrhage (8–10 weeks), inflammation, progressive fibrosis (10–20 weeks), and atrophy with diminished β-cells (38 weeks) are observed [22]. These inflammations are different from autoimmune-mediated inflammation observed in autoimmune diabetes. A major locus on chromosome 3 (Dmsdt1) was identified as a dominantly acting SDT allele that induces islet inflammation and fibrosis [26].


Pathophysiological characteristics of diabetic ocular complications in spontaneously diabetic torii rat.

Sasase T - J Ophthalmol (2010)

Nonfasting plasma insulin and glucose levels in Spontaneously Diabetic Torii (SDT) rats and control Sprague-Dawley (SD) rats. Diminish of pancreatic β-cells evokes hypoinsulinemia (a) and subsequent severe hyperglycemia (b) in SDT rats. Plasma glucose levels sharply increase at 15–20 weeks of age and eventually reach a plateau, approximately 800 mg/dL. Each value represents mean ± S.E.M. (N = 6–8).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2875698&req=5

fig1: Nonfasting plasma insulin and glucose levels in Spontaneously Diabetic Torii (SDT) rats and control Sprague-Dawley (SD) rats. Diminish of pancreatic β-cells evokes hypoinsulinemia (a) and subsequent severe hyperglycemia (b) in SDT rats. Plasma glucose levels sharply increase at 15–20 weeks of age and eventually reach a plateau, approximately 800 mg/dL. Each value represents mean ± S.E.M. (N = 6–8).
Mentions: Male SDT rats exhibit noticeable hyperglycemia, polyuria, and glucosuria concomitant with diminished blood insulin levels and decreased body weight by 15–20 weeks of age (Figure 1). The cumulative incidence of diabetes reaches 100% up to 40 weeks of age. In contrast, the incidence is 33% in female SDT rats [13]. Preceding the onset of diabetes, glucose intolerance with impaired insulin secretion [13, 22] and impaired lipid catabolism [23] are also observed. Genetic analysis for diabetes in SDT rats identified significant quantitative trait loci (QTL) (Gisdt1, Gisdt2, and Gisdt3) for glucose intolerance on rat chromosomes 1, 2, and X, respectively, indicating that the diabetic features in SDT rat are polygenically inherited [24]. Hyperglycemia in SDT rat is spontaneously developed, predominantly due to an insulin secretory defect resulting from pathological damage to the pancreatic islets, especially β-cells [22, 25]. Following primary microvascular events in the pancreatic islet such as congestion and hemorrhage (8–10 weeks), inflammation, progressive fibrosis (10–20 weeks), and atrophy with diminished β-cells (38 weeks) are observed [22]. These inflammations are different from autoimmune-mediated inflammation observed in autoimmune diabetes. A major locus on chromosome 3 (Dmsdt1) was identified as a dominantly acting SDT allele that induces islet inflammation and fibrosis [26].

Bottom Line: The Spontaneously Diabetic Torii (SDT) rat, a nonobese type 2 diabetes model, develops severe diabetic retinopathy as result of chronic severe hyperglycemia.Distinctive features in SDT rat are hypermature cataract, tractional retinal detachment with fibrous proliferation, and massive hemorrhaging in the anterior chamber.These pathophysiological changes are caused by sustained hyperglycemic condition and subsequent increased expression of vascular endothelial growth factor (VEGF) in retina, iris, and ciliary body.

View Article: PubMed Central - PubMed

Affiliation: Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.

ABSTRACT
The Spontaneously Diabetic Torii (SDT) rat, a nonobese type 2 diabetes model, develops severe diabetic retinopathy as result of chronic severe hyperglycemia. Although existing diabetes animal models also develop ocular complications, severe retinal lesions frequently observed in human diabetes patients such as preretinal neovascularization or retinal detachment are not found. Distinctive features in SDT rat are hypermature cataract, tractional retinal detachment with fibrous proliferation, and massive hemorrhaging in the anterior chamber. These pathophysiological changes are caused by sustained hyperglycemic condition and subsequent increased expression of vascular endothelial growth factor (VEGF) in retina, iris, and ciliary body. Although some differences in diabetic retinopathy exist between SDT rats and humans (e.g., a low incidence of neovascular formation and poor development of nonperfused area are found in this animal), SDT rat will be a useful model in studies of the pathogenesis and treatment of diabetic retinopathy.

No MeSH data available.


Related in: MedlinePlus