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

S. G. Paule, B. Nikolovski, R. E. Gray, J. P. Ludeman, A. Freemantle, R. A. Spark, J. B. Kerr, F. M. Ng, P. Z. Zimmet, M. A. Myers

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

In the early 1970s, a peptide fraction with insulin potentiating activity was purified from human urine but the identity and origins of the active constituent remained unknown. Here we identify the active component and characterize its origins. The active peptide was identified as an alpha amidated tetrapeptide with the sequence GHTD-amide. The peptide was synthesized and tested for stimulation of glycogen synthesis and insulin potentiation by insulin tolerance testing in insulin-deficient rats, which confirmed GHTD-amide as the active peptide. Tissue localization using a peptide-specific anti-serum and epifluorescent and confocal microscopy showed decoration of pancreatic islets but not other tissues. Confocal microscopy revealed co-localization with insulin and immunogold and electron microscopy showed localization to dense core secretory granules. Consistent with these observations GHTD-amide was found in media conditioned by MIN6 islet beta cells. Sequence database searching found no annotated protein in the human proteome encoding a potential precursor for GHTD-amide. We conclude that the insulin potentiating activity originally described in human urine is attributable to the tetrapeptide GHTD-amide. GHTD-amide is a novel peptide produced by pancreatic beta cells and no precursor protein is present in the annotated human proteome. Stimulation of glycogen synthesis and co-localization with insulin in beta cells suggest that GHTD-amide may play a role in glucose homeostasis by enhancing insulin action and glucose storage in tissues.

LanguageEnglish
Pages955-961
Number of pages7
JournalPeptides
Volume30
Issue number5
DOIs
Publication statusPublished - 1 May 2009

Keywords

  • Alpha amidation
  • Insulin
  • Islets of Langerhan
  • Pancreatic beta cell
  • Peptide

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

Cite this

Paule, S. G., Nikolovski, B., Gray, R. E., Ludeman, J. P., Freemantle, A., Spark, R. A., ... Myers, M. A. (2009). GHTD-amide: A naturally occurring beta cell-derived peptide with hypoglycemic activity. Peptides, 30(5), 955-961. https://doi.org/10.1016/j.peptides.2008.12.022
Paule, S. G. ; Nikolovski, B. ; Gray, R. E. ; Ludeman, J. P. ; Freemantle, A. ; Spark, R. A. ; Kerr, J. B. ; Ng, F. M. ; Zimmet, P. Z. ; Myers, M. A. / GHTD-amide : A naturally occurring beta cell-derived peptide with hypoglycemic activity. In: Peptides. 2009 ; Vol. 30, No. 5. pp. 955-961.
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Paule, SG, Nikolovski, B, Gray, RE, Ludeman, JP, Freemantle, A, Spark, RA, Kerr, JB, Ng, FM, Zimmet, PZ & Myers, MA 2009, 'GHTD-amide: A naturally occurring beta cell-derived peptide with hypoglycemic activity', Peptides, vol. 30, no. 5, pp. 955-961. https://doi.org/10.1016/j.peptides.2008.12.022

GHTD-amide : A naturally occurring beta cell-derived peptide with hypoglycemic activity. / Paule, S. G.; Nikolovski, B.; Gray, R. E.; Ludeman, J. P.; Freemantle, A.; Spark, R. A.; Kerr, J. B.; Ng, F. M.; Zimmet, P. Z.; Myers, M. A.

In: Peptides, Vol. 30, No. 5, 01.05.2009, p. 955-961.

Research output: Contribution to journalArticle

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AU - Paule, S. G.

AU - Nikolovski, B.

AU - Gray, R. E.

AU - Ludeman, J. P.

AU - Freemantle, A.

AU - Spark, R. A.

AU - Kerr, J. B.

AU - Ng, F. M.

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Paule SG, Nikolovski B, Gray RE, Ludeman JP, Freemantle A, Spark RA et al. GHTD-amide: A naturally occurring beta cell-derived peptide with hypoglycemic activity. Peptides. 2009 May 1;30(5):955-961. https://doi.org/10.1016/j.peptides.2008.12.022