Delta sleep-inducing peptide

Delta sleep-inducing peptide
Symbol DSIP
UniProt P01158

Delta sleep-inducing peptide, abbreviated DSIP, is a neuropeptide that when infused into the mesodiencephalic ventricle of recipient rabbits induces spindle and delta EEG activity and reduced motor activities.[1]

Its aminoacid sequence is Тrр-Аlа-Gly-Gly-Asp-Ala-Ser-Gly-Glu. However, the gene is unknown, raising serious questions regarding the actual existence of this peptide in nature.


Delta sleep-inducing peptide was first discovered in 1974 by the Swiss Schoenenberger-Monnier group who isolated it from the cerebral venous blood of rabbits in an induced state of sleep. It was primarily believed to be involved in sleep regulation due to its apparent ability to induce slow-wave sleep in rabbits, but studies on the subject have been contradictory.[2]

Delta-sleep-inducing peptide (DSIP)-like material has been found in human breast milk.[3]

Structure and Interactions

DSIP is an amphiphilic peptide of molecular weight 850 daltons with the amino acid motif:

It has been found in both free and bound forms in the hypothalamus, limbic system and pituitary as well as various peripheral organs, tissues and body fluids.[5] In the pituitary it co-localises with many peptide and non-peptide mediators such as corticotropin-like intermediate peptide (CLIP), adrenocorticotrophic hormone (ACTH), melanocyte-stimulating hormone (MSH), thyroid-stimulating hormone (TSH) and melanin concentrating hormone (MCH). It is abundant in the gut secretory cells and in the pancreas where it co-localises with glucagon.[4]

In the brain its action may be mediated by NMDA receptors.[6] In another study Delta sleep-inducing peptide stimulated Acetyltransferase activity through α1 receptors in rats.[7] It is unknown where DSIP is synthesized.

In vitro it has been found to have a low molecular stability with a half life of only 15 minutes due to the action of a specific aminopeptidase-like enzyme.[8] It has been suggested that in the body it complexes with carrier proteins to prevent degradation, or exists as a component of a large precursor molecule,[9] but as yet no structure or gene has been found for this precursor.

Evidence supports the current belief that it is regulated by glucocorticoids.[10]

Gimble et al. suggest that DSIP interacts with components of the MAPK cascade and is homologous to glucocorticoid-induced leucine zipper (GILZ).[11] GILZ can be induced by Dexamethasone. It prevents Raf-1 activation, which inhibits phosphorylation and activation of ERK.[12]


Many roles for DSIP have been suggested following research carried out using peptide analogues with a greater molecular stability[13] and through measuring DSIP-like immunological (DSIP-LI) response by injecting DSIP antiserum and antibodies.[14]

Roles in endocrine regulation

Roles in physiological processes

Roles in disease and medicine

Safety and possible side-effects of long-term DSIP use haven't been established in clinical research studies.


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  2. Schoenenberger GA, Maier PF, Tobler HJ, Monnier M (1977). "A naturally occurring delta-EEG enhancing nonapeptide in rabbits". European Journal of Physiology. 369 (2): 99–109. doi:10.1007/BF00591565. PMID 560681.
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  4. 1 2 Kovalzon VM, Strekalova TV (2006). "Delta sleep-inducing peptide (DSIP): a still unresolved riddle". Journal of Neurochemistry. 97 (2): 303–309. doi:10.1111/j.1471-4159.2006.03693.x. PMID 16539679.
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  13. synthesized by V. N. Kalikhevich and S. I. Churkina, University Chemical Institute, St. Petersburg, Russia, and I. I. Mikhaleva and I. A. Prudchenko, Institute of Bio-organic Chemistry, Russian Academy of Sciences, Moscow
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