DSIP

Research summary

DSIP (delta sleep-inducing peptide) is a nine-amino-acid peptide, Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu, isolated in 1977 from the cerebral venous blood of rabbits in which sleep had been induced by brain stimulation. It was named for its ability to enhance slow-wave (delta) EEG activity in those rabbits, but its link to sleep has stayed weakly documented and human findings are mixed. Peptides Only supplies DSIP as a lyophilized compound for laboratory research only.

Also known as

Delta sleep-inducing peptide · Emideltide · Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu

Sequence

Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu

What is DSIP?

Delta sleep-inducing peptide was characterized in 1977 by Guido Schoenenberger and Marcel Monnier in Basel. They isolated it from a dialysate of cerebral venous blood taken from rabbits during electrical stimulation of the intralaminar thalamus, a procedure used to induce sleep, and determined its sequence as Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu^1,2.

In double-blind rabbit experiments, synthetic DSIP infused into the brain ventricles increased delta and spindle EEG activity, while five possible metabolic fragments and several analogs did not. Only the alpha-aspartyl form of the peptide was highly active; its beta-aspartyl isomer was not^1,2.

Its structure is unlike that of any other known peptide family³. Antibodies raised against DSIP detect DSIP-like immunoreactivity in brain, peripheral organs and plasma of several mammals⁴, but when researchers purified a large immunoreactive molecule from pig brain it proved to be an unrelated 77-residue protein with a leucine-zipper motif⁵. The confusion persists in gene names: the glucocorticoid-induced leucine zipper (GILZ) gene is also known as the delta sleep-inducing peptide immunoreactor⁶.

What the research has examined

Early animal work, reviewed in 1984, reported that DSIP promoted mainly delta sleep in rabbits, rats and mice, with a U-shaped response curve, and also affected electrophysiological activity, brain neurotransmitter levels, circadian and locomotor patterns, hormone levels and responses to other drugs, including withdrawal⁴.

Human physiology studies have not supported a simple sleep-hormone role. In 12 healthy volunteers sampled every 30 minutes for 24 hours at the US National Institutes of Health, plasma DSIP-like immunoreactivity peaked in the afternoon, tracked body temperature closely, and was lower, not higher, during REM and slow-wave sleep than during wakefulness⁷.

Stability is another complication. DSIP is degraded quickly in human and rat blood, while some analogs persist longer, and the researchers who measured this suggested that inactivation rates could contribute to variable results in vivo⁸. Russian groups have continued to study DSIP in stress and aging models; in one, repeated administration in rats aged 2 to 24 months was associated with higher expression of the antioxidant-enzyme genes Sod1 and Gpx1 in brain and blood cells⁹.

Human studies: mixed results

The first human studies, run in the early 1980s with the Basel group, gave DSIP intravenously under double-blind conditions in five studies. They described it as well tolerated and reported sleep-promoting effects in insomniac patients, along with changes in alertness and performance during waking¹⁰.

Later work was less encouraging. A double-blind, placebo-controlled study from the University of Amsterdam in 16 chronic insomniac patients found only weak effects on sleep efficiency and sleep latency, partly attributable to an incidental change in the placebo group, and no change in subjective sleep quality. The authors concluded that short-term DSIP was unlikely to be of major therapeutic value¹¹.

In a randomized 2009 study in 24 patients under isoflurane anesthesia, DSIP did the opposite of what its name suggests: it reduced EEG delta rhythm, lightened anesthetic depth as measured by the bispectral index, increased heart rate and reduced heart rate variability¹².

Limitations: what is not known

A 2006 review in the Journal of Neurochemistry called DSIP a still unresolved riddle. No DSIP gene, precursor protein or receptor had been isolated, and the hypothesis that DSIP is a natural sleep factor was described as extremely poorly documented. The authors also noted that in their own rabbit and rat studies certain synthetic DSIP analogs, but not DSIP itself, significantly promoted slow-wave sleep³.

• Where DSIP comes from in the body is unknown, and antibody-based measurements may detect unrelated molecules^3,5.
• Human studies are small, mostly decades old, and their results conflict^10,11,12.
• DSIP is degraded rapidly in blood, which complicates interpretation of in vivo results⁸.
• DSIP is not approved as a medicine by the FDA or the European Medicines Agency.

Sourcing DSIP for research

DSIP is listed with our research peptides. Every lot is independently tested and ships from the USA with a lot-matched certificate of analysis showing HPLC purity and mass-spec identity, published in our certificate library. Researchers working on circadian and pineal endpoints may also want to compare Epithalon, discussed in Epitalon vs Pinealon.