DSIP (Delta Sleep-Inducing Peptide)

Delta Sleep-Inducing Peptide (DSIP) is a naturally occurring peptide composed of nine amino acids, originally isolated from the central nervous system in experimental models of electrically induced sleep. As its name suggests, DSIP has been proposed to play a role in regulating sleep cycles, particularly by promoting delta (deep) sleep. In addition to its potential influence on sleep, the peptide has also been suggested to participate in broader physiological processes, including modulation of electrophysiological brain activity and possible regulation of neurotransmitter levels.(1)

DSIP was first identified and studied between 1963 and 1977 and has since remained a subject of ongoing scientific investigation.(2) While it was initially explored primarily for its potential as a sleep-inducing factor, subsequent research has suggested a wider range of possible effects, including roles in pain modulation, regulation of sleep patterns, and mitigation of withdrawal-related symptoms.(3)

Mechanisms of Action

DSIP is proposed to influence both the structure and quality of sleep through its interaction with the central nervous system. It is thought that the peptide may reduce sleep latency—the time required to fall asleep—and potentially improve overall sleep quality by modulating the activity of various neurotransmitters within the brain. Despite these proposed effects, the precise mechanisms and pathways through which DSIP operates have not yet been fully established.

Current hypotheses suggest that DSIP may exert its actions by interacting with specific receptor systems that are considered important to its function. These include:

  • N-methyl-D-aspartate (NMDA) receptors and gamma-aminobutyric acid (GABA) receptors: NMDA receptors are linked to glutamate, a vital neurotransmitter that facilitates brain excitation, while GABA receptors are associated with inhibitory neurotransmission, playing a significant role in calming the brain. Research conducted on murine models has suggested that DSIP might amplify GABA's calming actions, which assists in reducing brain activity and helps individuals fall asleep more easily. Concurrently, murine studies suggest that DSIP may dampen some of the stimulatory impacts of NMDA receptors, thereby decreasing overall brain stimulation and further aiding in sleep promotion.(4)(5)

  • Opioid receptors: Further research indicates that DSIP might indirectly affect opioid receptors in the brain. This interaction is believed to influence the peptide's ability to modulate sleep and alleviate withdrawal symptoms, highlighting its complex involvement in the brain's signaling systems.(6)(7)

  • Alpha 1-adrenergic receptor: This receptor, apparently found in the pineal gland, has been another focus of DSIP research. An experimental study has suggested that DSIP's modulation of the alpha 1-adrenergic receptor could be a mechanism through which it affects sleep patterns. This interaction also hints at DSIP's potential role in managing stress tolerance, given the significant influence of alpha 1-adrenergic signaling in stress-related processes.(8)

  • These findings underline the complex and multifaceted ways in which DSIP might influence sleep and stress management, although more research is needed to understand its mechanisms of action.

Chemical Makeup

  • Molecular Formula: C35H48N10O15

  • Molecular Weight: 848.82 g/mol

  • Other Known Titles: DSIP nonapeptide; emideltide

Research and Clinical Studies
DSIP and Sleep Cycles

A study(9) conducted on feline models investigated the potential effects of DSIP on sleep patterns. The subjects were divided into two groups: a control group and a DSIP-treated group. Following administration of the peptide, the animals were monitored over an eight-hour period. The results suggested a significant increase in total sleep time and slow wave sleep (SWS) within the DSIP group. This effect appeared rapidly, with elevated SWS observed within the first hour of administration, maintained for approximately seven hours before declining in the eighth hour.

Slow wave sleep, commonly referred to as deep sleep, is considered a critical stage within overall sleep architecture. Sleep is typically divided into non-rapid eye movement (NREM) and rapid eye movement (REM) phases, which alternate cyclically throughout the night. SWS falls within the NREM category and is characterised by low-frequency, high-amplitude delta waves, as detected by electroencephalogram (EEG) recordings. NREM sleep itself consists of three stages—N1, N2, and N3—with N3 representing the deepest stage, synonymous with SWS. Following this phase, the sleep cycle transitions into REM sleep, where brain activity increases and dreaming occurs.

In addition, a clinical study(10) suggested that DSIP may increase sleep pressure shortly after administration, resulting in an approximate 59% increase in sleep within two hours of exposure. Researchers also proposed that the peptide may improve sleep efficiency, potentially by reducing the time required to fall asleep.

DSIP and Endocrine Regulation

DSIP has been proposed to interact with various hormonal messengers that are typically released during sleep. One example includes luteinizing hormone (LH), which plays a key role in the regulation of reproductive hormones such as testosterone. In a study involving murine models,(11) DSIP was evaluated for its potential effects on the endocrine system. Within approximately 30 minutes of administration, LH levels were observed to increase significantly, while no notable changes were detected in another regulatory hormone, follicle-stimulating hormone (FSH).

Additional research has suggested that DSIP may influence the secretion of growth hormone (GH), potentially through actions on the hypothalamus, which is responsible for regulating hormonal release. In studies using ovariectomized murine models—designed to eliminate the influence of gonadal steroids—DSIP exposure was associated with an apparent increase in GH levels. The involvement of dopaminergic pathways was proposed based on findings that pimozide, a dopamine antagonist, appeared to block the DSIP-induced rise in GH. Furthermore, in vitro experiments using pituitary cells demonstrated a similar increase in GH release following DSIP exposure, although this effect diminished at higher concentrations. These observations suggest that DSIP may have a complex role in GH regulation, potentially linking its activity to sleep-related hormonal release, particularly given its association with slow-wave sleep and the known relationship between this sleep phase and GH secretion.(12)

DSIP and Stress Response

Researchers have explored the potential effects of DSIP in murine models exposed to experimentally induced stress.(13) In this study, the subjects were divided into six groups: a control group receiving a placebo, and five additional groups receiving DSIP at varying time points relative to the stress exposure. These included administration one hour or 24 hours prior to the stress experiments, as well as one hour or 24 hours before the final stress exposure. The study focused on evaluating changes in key biochemical markers associated with the stress response, including substance P, beta-endorphin, and corticosterone.

The findings suggested that DSIP exposure may influence the levels of these markers, indicating a potential role in modulating stress responses. For example, beta-endorphin levels were observed to initially decrease and then rise significantly, suggesting a possible interaction with the opioidergic system that may contribute to stress adaptation or regulation. In addition, corticosterone levels—commonly used as an indicator of stress in murine models—appeared to decrease shortly after DSIP administration.

Overall, the study proposed that DSIP’s effects on substance P, beta-endorphin, and corticosterone may reflect a broader pattern of biochemical activity. These observations suggest that the peptide may initiate a series of molecular responses that contribute to its potential role in modulating stress-related processes.(13)

DSIP and Longevity

A study(14) conducted on murine models, divided equally between DSIP-treated and control groups, examined the peptide’s potential physiological effects. The researchers reported that DSIP did not appear to significantly alter food intake; however, it was associated with a reduction in body weight. Additional findings suggested a decrease in chromosomal aberrations within bone marrow cells by approximately 23%, alongside an increase in lifespan of around 24% compared to the control group. Furthermore, the incidence of malignancies appeared to be reduced by approximately 2.5-fold in the DSIP-treated models.

Another study proposed that the potential protective effects of DSIP may be linked to its antioxidative properties.(15) In murine models, DSIP exposure was associated with reduced levels of malonic dialdehyde, a byproduct of lipid peroxidation and a marker of oxidative stress. This observation suggested that DSIP may help limit lipid peroxidation, thereby exerting antioxidant effects. The peptide was also associated with stimulation of endogenous antioxidant systems, influencing both enzymatic and non-enzymatic components. Researchers noted that DSIP appeared to enhance the activity of key antioxidant enzymes such as superoxide dismutase, catalase, and ceruloplasmin, as well as increase levels of non-enzymatic antioxidants like urea and uric acid. These findings suggest that DSIP may support the body’s antioxidant defence systems, particularly in the context of ageing, where such systems are typically diminished.(15)

DSIP is available for research and laboratory purposes only. Please speak to our friendly research team to find out more and for sourcing options.

References:

  1. National Center for Biotechnology Information. "PubChem Compound Summary for CID 3623358, Emideltide;delta Sleep Inducing Peptide" PubChem,  https://pubchem.ncbi.nlm.nih.gov/compound/3623358

  2. Graf MV, Kastin AJ. Delta-sleep-inducing peptide (DSIP): an update. Peptides. 1986 Nov-Dec;7(6):1165-87.  https://pubmed.ncbi.nlm.nih.gov/3550726/

  3. Kovalzon VM, Strekalova TV. Delta sleep-inducing peptide (DSIP): a still unresolved riddle. J Neurochem. 2006 Apr;97(2):303-9.  https://pubmed.ncbi.nlm.nih.gov/16539679/

  4. Grigor'ev VV, Ivanova TA, Kustova EA, Petrova LN, Serkova TP, Bachurin SO. Effects of delta sleep-inducing peptide on pre- and postsynaptic glutamate and postsynaptic GABA receptors in neurons of the cortex, hippocampus, and cerebellum in rats. Bull Exp Biol Med. 2006 Aug;142(2):186-8. English, Russian. doi: 10.1007/s10517-006-0323-9. PMID: 17369935

  5. Sudakov KV, Umriukhin PE, Rayevsky KS. Delta-sleep inducing peptide and neuronal activity after glutamate microiontophoresis: the role of NMDA-receptors. Pathophysiology. 2004 Oct;11(2):81-86.  https://pubmed.ncbi.nlm.nih.gov/15364118/

  6. Nakamura A, Nakashima M, Sakai K, Niwa M, Nozaki M, Shiomi H. Delta-sleep-inducing peptide (DSIP) stimulates the release of immunoreactive Met-enkephalin from rat lower brainstem slices in vitro. Brain Res. 1989 Feb 27;481(1):165-8. doi: 10.1016/0006-8993(89)90498-8. PMID: 2706459.

  7. Dick P, Grandjean ME, Tissot R. Successful treatment of withdrawal symptoms with delta sleep-inducing peptide, a neuropeptide with potential agonistic activity on opiate receptors. Neuropsychobiology. 1983;10(4):205-8. doi: 10.1159/000118012. PMID: 6328354.

  8. Graf MV, Schoenenberger GA. Delta sleep-inducing peptide modulates the stimulation of rat pineal N-acetyltransferase activity by involving the alpha 1-adrenergic receptor. J Neurochem. 1987 Apr;48(4):1252-7. doi: 10.1111/j.1471-4159.1987.tb05654.x. PMID: 3029331.

  9. Susić V, Masirević G, Totić S. The effects of delta-sleep-inducing peptide (DSIP) on wakefulness and sleep patterns in the cat. Brain Res. 1987 Jun 30;414(2):262-70.  https://pubmed.ncbi.nlm.nih.gov/3620931/

  10. Schneider-Helmert D, Gnirss F, Monnier M, Schenker J, Schoenenberger GA. Acute and delayed effects of DSIP (delta sleep-inducing peptide) on human sleep behavior. Int J Clin Pharmacol Ther Toxicol. 1981 Aug;19(8):341-5.  https://pubmed.ncbi.nlm.nih.gov/6895513/

  11. Iyer KS, McCann SM. Delta sleep inducing peptide (DSIP) stimulates the release of LH but not FSH via a hypothalamic site of action in the rat. Brain Res Bull. 1987 Nov;19(5):535-8. doi: 10.1016/0361-9230(87)90069-4.  https://pubmed.ncbi.nlm.nih.gov/3121137/

  12. Iyer KS, McCann SM. Delta sleep-inducing peptide (DSIP) stimulates growth hormone (GH) release in the rat by hypothalamic and pituitary actions. Peptides. 1987 Jan-Feb;8(1):45-8. doi: 10.1016/0196-9781(87)90163-x. PMID: 3575154.

  13. Sudakov KV, Coghlan JP, Kotov AV, Salieva RM, Polyntsev YuV, Koplik EV. Delta-sleep-inducing peptide sequels in the mechanisms of resistance to emotional stress. Ann N Y Acad Sci. 1995 Dec 29;771:240-51.  https://pubmed.ncbi.nlm.nih.gov/8597403/

  14. Popovich IG, Voitenkov BO, Anisimov VN, Ivanov VT, Mikhaleva II, Zabezhinski MA, Alimova IN, Baturin DA, Zavarzina NY, Rosenfeld SV, Semenchenko AV, Yashin AI. Effect of delta-sleep inducing peptide-containing preparation Deltaran on biomarkers of aging, life span and spontaneous tumor incidence in female SHR mice. Mech Ageing Dev. 2003 Jun;124(6).  https://pubmed.ncbi.nlm.nih.gov/12782416/

  15. Bondarenko TI, Maĭboroda EA, Mikhaleva II, Prudchenko IA. [Mechanism of delta-sleep inducing peptide geroprotective activity]. Adv Gerontol. 2011;24(1):80-92. Russian.  https://pubmed.ncbi.nlm.nih.gov/21809625/

DSIP (Delta Sleep-Inducing Peptide)