GHTD-amide: a naturally occurring beta cell-derived peptide with hypoglycemic activity

Area of Science:

• Biochemistry
• Endocrinology
• Molecular Biology

Background:

• A peptide fraction with insulin potentiating activity was isolated from human urine in the 1970s.
• The identity and origin of this active constituent remained unknown for decades.

Purpose of the Study:

• To identify the active peptide responsible for insulin potentiation found in human urine.
• To characterize the cellular origins and biological function of this novel peptide.

Main Methods:

• Peptide identification and synthesis of the alpha amidated tetrapeptide GHTD-amide.
• In vivo testing in insulin-deficient rats to confirm glycogen synthesis stimulation and insulin potentiation.
• Tissue localization studies using immunofluorescence and electron microscopy in pancreatic islets and MIN6 cells.

Main Results:

• The active peptide was identified as GHTD-amide, a novel alpha amidated tetrapeptide.
• GHTD-amide demonstrated stimulation of glycogen synthesis and insulin potentiation in vivo.
• Localization studies revealed GHTD-amide within pancreatic beta cells, co-localizing with insulin in secretory granules.

Conclusions:

• The insulin potentiating activity in human urine is attributed to GHTD-amide.
• GHTD-amide is a novel peptide produced by pancreatic beta cells with no identified precursor protein in the human proteome.
• GHTD-amide's function suggests a role in glucose homeostasis by enhancing insulin sensitivity and glucose storage.