Successful And Reproducible Bioactivity With C-Peptide Via Activation With Zinc.

Overview

Diabetes is considered to be a major health problem throughout the world with its hallmark feature being hyperglycemia, or high blood glucose. Diabetes is classified into 2 general types- type 1 and type 2 diabetes. While both types of diabetes suffer similar complications, the cause of each type is vastly different. Type 1 diabetes, or juvenile diabetes, generally occurs during childhood or adolescence and is the result of an autoimmune destruction of the beta-cells. Conversely, type 2 diabetes is the result of ...
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Overview

Diabetes is considered to be a major health problem throughout the world with its hallmark feature being hyperglycemia, or high blood glucose. Diabetes is classified into 2 general types- type 1 and type 2 diabetes. While both types of diabetes suffer similar complications, the cause of each type is vastly different. Type 1 diabetes, or juvenile diabetes, generally occurs during childhood or adolescence and is the result of an autoimmune destruction of the beta-cells. Conversely, type 2 diabetes is the result of various factors including age, obesity, race, and family history. Patients who suffer from type 1, and in many cases type 2 diabetes, are required to take insulin injections to maintain proper blood glucose levels. Insulin is produced in the pancreas as proinsulin and is released into the bloodstream after an intake of glucose. Insulin, while effective at maintaining proper blood glucose levels, does not ameliorate many of the complications associated with diabetes. Proinsulin also consists of C-peptide which, since its discovery, has been thought to possess little biological activity. Within the past decade, however, there has been new evidence that C-peptide is indeed a biologically relevant peptide and has been shown to improve many of the complications associated with diabetes including neuropathy, nephropathy, retinopathy, and those associated with the microcirculation. Despite these advances, there has been no successful long-term clinical trial involving C-peptide replacement therapy, most likely due to difficulties with reproducibility. The lack of a successful long-term clinical trial is one reason C-peptide is not considered to be a biologically relevant peptide. As reported here, it has been determined that C-peptide requires proper preparation, namely the activation by a metal such as zinc, to provide reproducible results when incubated with the red blood cell (RBC), an unlikely factor in the pathophysiology of diabetes. Data reported here suggests that incubation of RBCs with metal-activated C-peptide has the ability to increase the release of ATP, a recognized stimulus of nitric oxide (a potent vasodilator), via an increase in glucose transport. Additional arguments against C-peptide include the lack of a receptor and the abundance of C-peptide in patients with type 2 diabetes. However, data presented here suggest that the lack of a known receptor does not mean that C-peptide is biologically irrelevant. Also, it has been determined during the course of this thesis that the membrane of the RBC from type 2 patients contains a higher amount of phosphatidylserine, which may result in repulsion between the membrane and C- peptide resulting in an apparent "C-peptide resistance". However, incubation of the RBCs with the most commonly prescribed drug to treat type 2 diabetes, metformin, prior to the addition of metal-activated C-peptide, appears to correct this resistance. Overall, data reported here offer solutions to the primary arguments against C- peptide as a biologically relevant peptide. The results offer potentially clinically relevant data, which may provide the foundation for a successful clinical trial of C-peptide replacement therapy.
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Product Details

  • ISBN-13: 9781243714442
  • Publisher: BiblioLabsII
  • Publication date: 9/8/2011
  • Pages: 158
  • Product dimensions: 7.44 (w) x 9.69 (h) x 0.34 (d)

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