Animal models of diabetes‐associated vascular diseases: an update on available models and experimental analysis

Choi, Judy S.Y.; Sharma, Arpeeta

doi:10.1111/bph.15591

Cited by 12 publications

(15 citation statements)

References 151 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Maybe it is a matter of diet (rodents eat mainly fibers), or maybe it is due to the different lipoprotein profiles in rodents (large amounts of HDL). Indeed, only T1DM rodents without a lipoprotein receptor (ApoE knock-out animals) develop atherosclerotic lesions after induction of T1DM [20]. This solid observation, replicated several times in different laboratories, significantly supports the idea that another prominent actor of atherosclerotic lesions in T1DM is dyslipidemia.…”

Section: Introduction: Why Hyperglycemia Cannot Explain Everything In...mentioning

confidence: 57%

Mechanisms of Diabetic Nephropathy Not Mediated by Hyperglycemia

Viggiano

2023

JCM

View full text Add to dashboard Cite

Diabetes mellitus (DM) is characterized by the appearance of progressive kidney damage, which may progress to end-stage kidney disease. The control of hyperglycemia is usually not sufficient to halt this progression. The kidney damage is quantitatively and qualitatively different in the two forms of diabetes; the typical nodular fibrosis (Kimmelstiel Wilson nodules) appears mostly in type 1 DM, whereas glomerulomegaly is primarily present in type 2 obese DM. An analysis of the different metabolites and hormones in type 1 and type 2 DM and their differential pharmacological treatments might be helpful to advance the hypotheses on the different histopathological patterns of the kidneys and their responses to sodium/glucose transporter type 2 inhibitors (SGLT2i).

show abstract

Section: Introduction: Why Hyperglycemia Cannot Explain Everything In...mentioning

confidence: 57%

Mechanisms of Diabetic Nephropathy Not Mediated by Hyperglycemia

Viggiano

2023

JCM

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

“…24 As one of the most significant microvascular complications in diabetic patients, DN is considered a metabolic and hemodynamic glomerular disease initiated by hyperglycemia, 25 and the overproduction of various inflammatory factors is involved in the pathogenesis of DN. 26 The current understanding of diabetes-driven vascular complications as well as therapeutic interventions has arisen from studying disease pathogenesis in animal models. The choice of an appropriate animal model is important.…”

Section: Discussionmentioning

confidence: 99%

TNF-α and IL-1β Promote Renal Podocyte Injury in T2DM Rats by Decreasing Glomerular VEGF/eNOS Expression Levels and Altering Hemodynamic Parameters

Wang¹,

Feng²,

Zhang³

et al. 2022

JIR

View full text Add to dashboard Cite

Purpose Diabetic nephropathy (DN) is a serious microvascular complication in those with type 2 diabetes mellitus (T2DM). Evidence confirms that serum tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the T2DM stage are proposed as prognostic markers for DN development, but it is unclear how they affect renal podocyte-associated nephrin and WT-1 expression. In the presence of podocyte injury, glomerular vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS) and hemodynamic parameters are dysregulated. The current research aimed to clarify the relationship of TNF-α and IL-1β with podocyte injury by altering VEGF/eNOS expression and hemodynamic parameters. Methods A high-fat diet/streptozotocin-induced DN rat model was established. Serum TNF-α and IL-1β levels were tracked in the pre-T2DM, T2DM and DN stages. In the DN stage, the mRNA and protein expression levels of renal TNF-α, IL-1β, VEGF, eNOS, nephrin and WT-1 were studied. Renal hemodynamic parameters, including peak systolic velocity, end-diastolic flow velocity and mean velocity were measured with a color Doppler ultrasound technique. Results Compared to those in the normal control (CTL) group, serum TNF-α and IL-1β levels increased significantly in the pre-T2DM stage (obesity, insulin resistance and hyperlipidemia), T2DM stage (hyperglycemia) and DN stage (abnormal renal functions) (all: P < 0.05) in the DN group. Serum TNF-α and IL-1β levels in the T2DM stage were significantly higher than those in the pre-T2DM stage (two: P < 0.05). Compared to the CTL group, renal nephrin, WT-1, TNF-α, IL-1β, eNOS and VEGF expression and hemodynamic parameters in the DN stage all showed significant differences separately (all: P < 0.05). Conclusion Increased serum and renal TNF-α and IL-1β levels played important roles in reducing renal nephrin and WT-1 expression levels, which may be related to the fact that the former affected renal VEGF/eNOS expression and blood flow parameters in the DN rats.

show abstract

“…11,12 To date, a number of preclinical animal models have been developed for diabetes and diabetic vascular complications. 13 However, animal models do not always faithfully recapitulate the human condition, which has contributed to the lack of clinical translational success in this area. 14 Development of human disease models that are representative of diabetic endothelial dysfunction in vitro will complement the current preclinical animal models and facilitate therapeutic discovery to restore the endothelial function in diabetes.…”

Section: Introductionmentioning

confidence: 99%

“…Endothelial dysfunction—characterized by a reduction of nitric oxide bioavailability, an increase in reactive oxygen species (ROS) and a pro‐inflammatory, pro‐thrombotic milieu—is a key marker in all forms of diabetic vascular complications 11,12 . To date, a number of preclinical animal models have been developed for diabetes and diabetic vascular complications 13 . However, animal models do not always faithfully recapitulate the human condition, which has contributed to the lack of clinical translational success in this area 14 .…”

Section: Introductionmentioning

confidence: 99%

Modeling diabetic endothelial dysfunction with patient‐specific induced pluripotent stem cells

Gorashi,

Rivera‐Bolanos,

Dang

et al. 2023

Bioengineering & Transla Med

View full text Add to dashboard Cite

Diabetes is a known risk factor for various cardiovascular complications, mediated by endothelial dysfunction. Despite the high prevalence of this metabolic disorder, there is a lack of in vitro models that recapitulate the complexity of genetic and environmental factors associated with diabetic endothelial dysfunction. Here, we utilized human induced pluripotent stem cell (iPSC)‐derived endothelial cells (ECs) to develop in vitro models of diabetic endothelial dysfunction. We found that the diabetic phenotype was recapitulated in diabetic patient‐derived iPSC‐ECs, even in the absence of a diabetogenic environment. Subsequent exposure to culture conditions that mimic the diabetic clinical chemistry induced a diabetic phenotype in healthy iPSC‐ECs but did not affect the already dysfunctional diabetic iPSC‐ECs. RNA‐seq analysis revealed extensive transcriptome‐wide differences between cells derived from healthy individuals and diabetic patients. The in vitro disease models were used as a screening platform which identified angiotensin receptor blockers (ARBs) that improved endothelial function in vitro for each patient. In summary, we present in vitro models of diabetic endothelial dysfunction using iPSC technology, taking into account the complexity of genetic and environmental factors in the metabolic disorder. Our study provides novel insights into the pathophysiology of diabetic endothelial dysfunction and highlights the potential of iPSC‐based models for drug discovery and personalized medicine.

show abstract

Animal models of diabetes‐associated vascular diseases: an update on available models and experimental analysis

Cited by 12 publications

References 151 publications

Mechanisms of Diabetic Nephropathy Not Mediated by Hyperglycemia

Mechanisms of Diabetic Nephropathy Not Mediated by Hyperglycemia

TNF-α and IL-1β Promote Renal Podocyte Injury in T2DM Rats by Decreasing Glomerular VEGF/eNOS Expression Levels and Altering Hemodynamic Parameters

Modeling diabetic endothelial dysfunction with patient‐specific induced pluripotent stem cells

Contact Info

Product

Resources

About