Differential effects of proinsulin C-peptide fragments on Na +, K +-ATPase activity of renal tubule segments

Summary Proinsulin C-peptide has been shown to stimulate the activity of Na ⁺ K ⁺ ATPase of rat renal tubule segments. Thirty-six peptides and amino acids, corresponding to parts of the intact rat C-peptide and suitable controls were screened for capacity to stimulate Na ⁺, K ⁺-ATPase in an attempt to determine potential active sites in the C-peptide molecule. The carboxy-terminal tetra and penta peptides were found to elicit 92–103 % of the intact molecule's activity, and the remaining segment, des-(27–31) C-peptide, did not possess stimulatory activity. Peptides from the middle C-peptide segment, however, centering around a GGPEAG sequence, stimulated Na ⁺, K ⁺-ATPase activity (36–80 % of the intact molecule's effect) but this effect was not balanced by corresponding inactivity of other parts. Furthermore, it was paralleled by activity of a non-native dipeptide d-form. It is concluded that the latter effect and that of the middle segment may represent complex interactions other than the apparently specific effects of the C-terminal segment. [Diabetologia (1998) 41: 287–291] Received: 31 July 1997 and in revised form: 30 October 1997