In recent years, various biological activities of C-peptide have been confirmed, e.g., its ability to improve skin capillary blood flow in the feet, increase microvascular blood flow and oxygen uptake in the exercising forearm, decrease urinary albumin excretion, and improve nerve function in patients with type 1 diabetes (1,2). Furthermore, C-peptide stimulates glucose transport in human muscle strips of nondiabetic and diabetic subjects (3). Using a sequential insulin clamp technique, Li et al. (4) demonstrated that C-peptide in physiological concentrations stimulates body glucose utilization in diabetic rats. In a recent investigation by Grunberger et al. (5), C-peptide was shown to activate insulin receptor tyrosine kinase, insulin receptor substrate-1, tyrosine phosphorylation, phosphatidylinositol 3-kinase, mitogen-activated protein kinase phosphorylation, p90 Rsk (90-kDa ribosomal 56 protein kinase), and glycogen synthase kinase-3 phosphorylation. In addition, C-peptide mimics the effect of insulin, such as glycogen synthesis and amino acid uptake in rat muscle cells. However, in clinical studies involving C-peptide treatment for 1 or 3 months …