C-peptide modifies leptin and visfatin secretion in human adipose tissue.

Objective: The effects of C-peptide on adipose tissue, an organ involved in the development of obesity and insulin resistance, are not yet well known. The aim of this study was to determine whether C-peptide could be involved in the regulation of the adipocytokine synthesis in human visceral adipose tissue.

Methods: The association between C-peptide and different serum adipocytokines, with an intravenous glucose tolerance test (IVGTT), and in an in vitro study in subjects without obesity and in subjects with morbid obesity were analyzed.

Results: In different multiple regression analysis models, C-peptide and C-peptide increase above basal levels during total IVGTT and between 0 and 10 min were associated positively with leptin and negatively with visfatin. Rhodamine-labeled C-peptide binds to human adipocytes, and this binding was blocked with excess of unlabeled C-peptide. Exposure of human visceral explants and adipocytes from subjects with morbid obesity to C-peptide at 1 and 10 nM induced a significant increase in leptin and a decrease in visfatin secretion. In subjects without obesity, these C-peptide effects were found mainly at 10 nM. These effects can be inhibited by phosphatidylinositol 3-kinase (PI3K) or protein kinase B (PKB) inhibitors.

Conclusions: C-peptide may be involved in the regulation of leptin and visfatin secretion, molecules intimately involved in energy homeostasis processes, through PI3K or PKB pathways.