Impaired Proliferation, Apoptosis, and Angiogenesis of Adipose-Derived Stem Cells Isolated from Rats during the Course of Diabetes

Background: To characterize the impaired of proliferation, apoptosis, and angiogenic activity in ASCs isolated at different stages of the disease course from rats with type 1 diabetes mellitus (T1DM) rats induced by streptozotocin (STZ). Methods: Adipose tissues of the epididymis were harvested at 0, 4, 8, 12, and 16 weeks after the induction of T1DM in rats and from normal rats at the same time points and the morphological variations were detected by Oil red O staining. ASCs were collected from adipose tissues. Cell proliferation, apoptosis, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) expression were assessed. Results: With the prolongation of the disease course, the size and the morphology of adipocytes were distorted, and intracellular lipid droplets became smaller. After 4 weeks, the proliferation of ASCs was decreased, while apoptosis in ASCs was increased. Furthermore, as the disease proceeded, proliferation decreased and apoptosis increased. VEGF and bFGF expression in ASCs from diabetic rats was downregulated at 8 weeks. Conclusion: At 4 weeks after T1DM induction, the proliferation of ASCs decreased and apoptosis increased. The expression of angiogenic factors in ASCs declined at 8 weeks after T1DM induction. The changes in the proliferation, apoptosis, and angiogenic activity are related to the prolongation of disease course.

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Des(1–3)IGF-1 Treatment Normalizes Type 1 IGF Receptor and Phospho-Akt (Thr 308) Immunoreactivity in Predegenerative Retina of Diabetic Rats

Experimental Diabesity Research ◽

10.1080/15438600303729 ◽

2003 ◽

Vol 4 (1) ◽

pp. 45-57 ◽

Cited By ~ 8

Author(s):

A. Kummer ◽

B. E. Pulford ◽

D. N. Ishii ◽

G. M. Seigel

Keyword(s):

Growth Factor ◽

Ganglion Cell Layer ◽

Systemic Treatment ◽

Diabetic Rats ◽

Vascular Endothelial ◽

Diabetic Retina ◽

Igf Receptor ◽

Endothelial Growth Factor ◽

Biochemical Abnormalities

Little is known about interventions that may prevent predegenerative changes in the diabetic retina. This study tested the hypothesis that immediate, systemic treatment with an insulin-like growth factor (IGF)-1 analog can prevent abnormal accumulations of type 1 IGF receptor, and phospho-Akt (Thr 308) immunoreactivity in predegenerative retinas of streptozotocin (STZ) diabetic rats. Type 1 IGF receptor immunoreactivity increased approximately 3-fold in both inner nuclear layer (INL) and ganglion cell layer (GCL) in retinas from STZ rats versus nondiabetic controls. Phospho-Akt (Thr 308) immunoreactivity increased 5-fold in GCL and 8-fold in INL of STZ rat retinas. In all cases, immunoreactive cells were significantly reduced in STZ des(1–3)IGF-1–treated versus STZ rats. Preliminary results suggested that vascular endothelial growth factor (VEGF) levels may also be reduced. Hyperglycemia/ failure of weight gain in diabetic rats continued despite systemic des(1–3)IGF-1. These data show that an IGF-1 analog can prevent early retinal biochemical abnormalities implicated in the progression of diabetic retinopathy, despite ongoing hyperglycemia.

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