Abstract
Insulin and C-peptide are released in equimolecular concentrations in the circulation
after food ingestion as they result from the enzymatic cleavage of proinsulin. In
the brain, insulin inhibits food intake through hypothalamic receptors. In the present
study, we tested the ability of C-peptide to modulate food intake when injected in
the brain lateral ventricle of Long-Evans rats. For this purpose, 10 adult male rats
(BW 320 - 350 g) were deprived of food overnight. They were intra-cerebroventricularly
injected with 10 μg C-pepitde or vehicle (artificial cerebrospinal fluid [CSF]) during
the first hour of the light period and chow intake was measured 1, 3, 6 and 24 hours
after injection. Chow availability immediately triggered food consumption. Food intake
was not different between CSF- and C-peptide-injected rats either after one hour (5.7
± 0.6 g [CSF] vs. 6.7 g ± 0.5 g; ns) or after 24 hrs (23.3 ± 1.4 g [CSF] vs. 25.1
g ± 1.4 g; ns). In addition, a higher dose (20 μg/rat) had no effect at all in satiated
rats one hour after injection or later contrary to the 100 % increase measured after
injection of 2 μg of neuropeptide Y. Thus, we conclude that contrary to insulin, C-peptide
does not regulate feeding behaviour in normal rats whatever their insulin status.
Key words
Fasting - neuropeptide Y - neuropeptide S - ghrelin - leptin
References
- 1
Kitabchi A E.
Proinsulin and C-peptide: a review.
Metabolism.
1977;
26
547-587
- 2
Steiner D F.
The proinsulin C-peptide - a multirole model.
Exp Diabesity Res.
2004;
5
7-14
- 3
Wahren J.
C-peptide: new findings and therapeutic implications in diabetes.
Clin Physiol Funct Imaging.
2004;
24
180-189
- 4
Grunberger G, Qiang X, Li Z. et al .
Molecular basis for the insulinomimetic effects of C-peptide.
Diabetologia.
2001;
44
1247-1257
- 5
Zierath J R, Handberg A, Tally M, Wallberg-Henriksson H.
C-peptide stimulates glucose transport in isolated human skeletal muscle independent
of insulin receptor and tyrosine kinase activation.
Diabetologia.
1996;
39
306-313
- 6
Schwartz M W, Figlewicz D P, Baskin D G, Woods S C, Porte D J.
Insulin in the brain - a hormonal regulator of energy balance.
Endocr Rev.
1992;
13
387-414
- 7
Havrankova J, Roth J, Brownstein M.
Insulin receptors are widely distributed in the central nervous system of the rat.
Nature.
1978;
272
827-829
- 8
Beck B, Fernette B, Stricker-Krongrad A.
Peptide S is a novel potent inhibitor of voluntary and fast-induced food intake in
rats.
Biochem Biophys Res Comm.
2005;
332
859-865
- 9
Stricker-Krongrad A, Max J P, Musse N, Nicolas J P, Burlet C, Beck B.
Increased threshold concentrations of neuropeptide Y for a stimulatory effect on food
intake in obese Zucker rats - changes in the microstructure of the feeding behavior.
Brain Res.
1994;
660
162-166
- 10
Kaneko T, Munemura M, Oka H, Oda T, Suzuki S.
Demonstration of C-peptide immunoreactivity in various body fluids and clinical evaluation
of the determination of urinary C-peptide immunoreactivity.
Endocrinol Jpn.
1975;
22
207-212
- 11
Beck B.
KO’s and organisation of peptidergic feeding behavior mechanisms.
Neurosci Biobehav Rev.
2001;
25
143-158
- 12
Trayhurn P, Hoggard N, Mercer J G, Rayner D V.
Leptin: fundamental aspects.
Int J Obesity.
1999;
23
22-28
- 13
van der Lely A J, Tschop M, Heiman M L, Ghigo E.
Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin.
Endocr Rev.
2004;
25
426-457
- 14
Beck B, Richy S, Stricker-Krongrad A.
Ghrelin and body weight regulation in the obese Zucker rat in relation to feeding
state and dark/light cycle.
Exp Biol Med.
2003;
228
1124-1131
Dr. Bernard Beck
INSERM U724 · Faculté de Médecine
9, Avenue de la Forêt de Haye BP184 · 54505 Vandóuvre Cedex · France
Telefon: +33 (3) 83 68 33 31
Fax: +33 (3) 83 68 32 79 ·
eMail: Bernard.Beck@nancy.inserm.fr