Effects of C-peptide on isolated human pancreatic islet cells.
BACKGROUND
Recent data have demonstrated that pro-insulin-derived C-peptide can affect the function of several different cell types. We hypothesized that C-peptide might have an influence on the function and survival of isolated human islets.


METHODS
Islets were prepared by combining enzymatic digestion and density gradient centrifugation, and the effects of human C-peptide were evaluated acutely and after 24-h incubation. Insulin secretion, apoptosis, quantitative RT-PCR and western-blotting experiments were then performed.


RESULTS
Glucose-stimulated insulin secretion was not affected by C-peptide and, accordingly, mRNA expression of glucose transporter 2 and glucokinase did not differ between islets pre-cultured or not with the hormone. However, apoptosis was significantly lower in islets exposed to C-peptide than in control islets. This was accompanied by a significant increase of mRNA and protein expression of Bcl2, an anti-apoptotic molecule, with no change in the expression of Bax, a pro-apoptotic molecule.


CONCLUSIONS
These results show that in human islets pro-insulin C-peptide has no direct effects on insulin secretion, but it decreases islet cell apoptosis. A direct role of C-peptide on beta-cell mass regulation is therefore suggested.
Bugliani
Marco
M
Department of Endocrinology and Metabolism - Metabolic Unit, University of Pisa, Pisa, Italy.
Torri
Scilla
S
Lupi
Roberto
R
Del Guerra
Silvia
S
Grupillo
Maria
M
Del Chiaro
Marco
M
Mosca
Franco
F
Boggi
Ugo
U
Del Prato
Stefano
S
Marchetti
Piero
P
D017209:Apoptosis / Q000187:drug effects; D002096:C-Peptide / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
D002096:C-Peptide; D007328:Insulin; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein