tailieunhanh - VASCULAR COMPLICATIONS OF DIABETES - PART 5

Trong nuôi cấy tế bào Schwann và chuột STZ đái tháo đường, IGF-1 thể hiện một tác dụng bảo vệ thông qua PI 3-kinase, trong việc ngăn ngừa apoptosis glucose qua trung gian tế bào thần kinh và Schwann. Cả hai STZ-tiểu đường và BB / W chuột phát triển tăng đường huyết nghiêm trọng và thiếu hụt trong lưu thông | CHAPTER 9 PATHOPHYSIOLOGY OF DIABETIC NEUROPATHY 89 Insulin like growth factors IGFs In cultured Schwann cells and the STZ-diabetic rat IGF-1 demonstrates a protective effect via PI 3-kinase in preventing glucose-mediated neuronal and Schwann cell apoptosis. Both the STZ-diabetic and BB W rat develop severe hyperglycaemia and a deficiency in circulating IGF-I levels with neuroaxonal dystrophy NAD in the nerve terminals of the prevertebral sympathetic ganglia and the distal portions of noradrenergic ileal mesenteric nerves. In contrast the Zucker Diabetic Fatty ZDF rat an animal model of type 2 diabetes also develops severe hyperglycaemia but maintains normal levels of plasma IGF-I and does not demonstrate NAD in sympathetic ganglia and ileal mesenteric nerves. However IGF-I and IGF-I receptor mRNA levels have not been shown to differ in the sural nerve of diabetic patients compared with control subjects. C-Peptide In experimental studies C-peptide has demonstrated effects on Na K -ATPase activity endothelial nitric oxide synthase expression of neurotrophic factors and regulation of molecules controlling degeneration of the nodal apparatus in Type 1 diabetic nerves as well as DNA binding of transcription factors and modulation of apoptotic phenomena. These findings have recently been effectively translated into benefits in patients with Type 1 diabetes with the demonstration of a significant improvement in sural sensory nerve conduction velocity and vibration perception but without a benefit in either cold or heat perception after 12 weeks of daily subcutaneous C-peptide treatment. Vascular endothelial growth factor VEGF VEGF was originally discovered as an endothelial-specific growth factor with a predominant role in angiogenesis. However recent observations indicate that VEGF also has direct effects on neurones and glial cells stimulating their growth survival and axonal outgrowth. Thus with its potential for a dual impact on both the vasculature and neurones it .