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Somatostatin-28

● Clinical (analog context)
Somatostatin-28
Also known as: SS-28, Big Somatostatin, Preprosomatostatin Fragment
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Quick Summary

Somatostatin-28 (SS-28) is the 28-amino acid form of somatostatin produced primarily by intestinal L-cells and D-cells of the pancreas. It contains the complete SS-14 sequence at its C-terminus with an N-terminal extension of 14 amino acids.

GI Peptide / Neuroendocrine Preclinical / Clinical
Somatostatin-28 (SS-28) is the 28-amino acid form of somatostatin produced primarily by intestinal L-cells and D-cells of the pancreas. It contains the complete SS-14 sequence at its C-terminus with an N-terminal extension of 14 amino acids. SS-28 is the predominant circulating form in the portal vein after meals and has distinct receptor pharmacology from SS-14, with higher affinity for SSTR5 and a longer plasma half-life, making it a more important GI hormone than previously recognized.
Storage Stability
Lyophilized
1–2 years (-20°C)
Reconstituted
~30 days (2–8°C)
Room temp
Avoid

Mechanism of Action

Preferential SSTR5 Activation

SS-28 binds SSTR1-5 but shows significantly higher affinity for SSTR5 compared to SS-14. SSTR5 is highly expressed in pancreatic beta-cells and gut endocrine cells. This SSTR5 preference makes SS-28 a more potent inhibitor of postprandial insulin secretion than SS-14 at equivalent concentrations, contributing to blood glucose regulation during meal absorption.

GI Hormone Inhibition

SS-28 released from intestinal D-cells after meals inhibits secretin, CCK, GIP, and GLP-1 secretion in a paracrine manner. This broad inhibition of nutrient-stimulated gut hormones modulates the rate of intestinal absorption and pancreatic secretion. SS-28 is thus a key brake on postprandial incretin responses.


Research Summary

Incretin Modulation

Preclinical

SS-28 is a more potent inhibitor of GLP-1 secretion from L-cells than SS-14. In the context of GLP-1-based therapies, SS-28 receptor activation represents an endogenous brake on incretin action. SSTR5 antagonists that block SS-28 effects could potentially enhance endogenous GLP-1 release, offering an oral approach to incretin-based diabetes therapy.

SSTR5 Pharmacology

Clinical

SSTR5-selective analogs developed to understand SS-28 biology include L-817,818 and other research compounds. SS-28 has been used to characterize SSTR5 expression in pancreatic NETs, which often overexpress SSTR5. The differential expression of SSTR subtypes in NET subtypes guides somatostatin analog selection for treatment.


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Research Protocols

GoalDoseFrequencyRoute
SSTR5 binding characterization0.1-100 nMSingleBinding assay
Insulin suppression1-10 nMSingleIslet incubation

SS-28 is a research tool and endogenous hormone. Clinical use references somatostatin analogs (octreotide, pasireotide).


Interactions

Related Form
Somatostatin-14
SS-28 contains SS-14 at C-terminus; distinct receptor selectivity (SSTR5 preference)
Inhibitory
GLP-1
SS-28 inhibits GLP-1 secretion from L-cells via paracrine SSTR5 signaling
Inhibitory
Insulin
More potent insulin secretion inhibitor than SS-14 via SSTR5 in beta-cells

Safety Profile

SS-28 is an endogenous GI hormone with a short plasma half-life. It shares the safety profile of somatostatin: risk of hypoglycemia (via insulin suppression at therapeutic doses), malabsorption, and gallstone formation with prolonged exposure. Clinical somatostatin analogs provide the relevant safety reference.


References

  • [1]Patel YC (1999). Somatostatin and its receptor family. Frontiers in Neuroendocrinology, 20(3), 157-198.
  • [2]Chessler SD et al. (2000). The regulation of somatostatin-28 versus somatostatin-14 processing by the SSTR5 receptor. Journal of Molecular Endocrinology, 24(2), 267-276.
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Verified Scientific Data Last audited:
Data Sources & External References
Source: peer-reviewed literature  ·  Domain: ascendpeptide.org

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