NEW ASPECTS ON BIOLOGICAL-ACTIVITY OF C-PEPTIDE IN IDDM PATIENTS

C-peptide, which is released from the pancreatic beta cells into the c irculation in amounts equimolar with insulin, fulfills an important fu nction in the assembly of the two-chain insulin structure, but has oth erwise been considered to be biologically inactive. However, during th e last few years several experimental and clinical studies have demons trated that replacement of C-peptide in patients with insulin-dependen t diabetes mellitus elicits several physiological effects. Thus, durin g shortterm substitution of C-peptide (1-3 h) decreased glomerular hyp erfiltration, augmented whole body and skeletal muscle glucose utilisa tion. improved autonomic nerve function and a redistribution of microv ascular skin blood flow could be observed. In addition: replacement of C-peptide during a period of 1-3 months has been shown to improve ren al function as well as autonomic and sensory nerve function in IDDM pa tients. The mechanisms behind these effects remain unclear, but recent investigations have indicated that an increase in Na(+)K(+)ATPase act ivity and a stimulation of the endothelial nitric oxide synthase may c ontribute to the observed physiological effects of C-peptide. Not only the intact C-peptide molecule, but also fragments from the C-terminal and mid-portion of the molecule have been shown to exert biological e ffects. Further research will be necessary to evaluate the underlying mechanism and the clinical impact of C-peptide replacement in IDDM pat ients.