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Abstract

  1. Top of page
  2. Abstract
  3. REFERENCES

Peptides of the glucagon/vasoactive-intestinal-peptide (VIP) peptide family share a considerable sequence similarity at their N-terminus. They either start with Tyr-Ala, His-Ala or His-Ser which might be in part potential targets for dipeptidyl-peptidase IV, a highly specialized aminopeptidase removing dipeptides only from peptides with N-terminal penultimate proline or alanine. Growthhormone-releasing factor(1–29)amide and gastric inhibitory peptide/glucose-dependent insulinotropic peptide (GIP) with terminal Tyr-Ala as well as glucagon-like peptide-1(7–36)amide/insulinotropin [GLP-1(7–36)amide] and peptide histidine methionine (PHM) with terminal His-Ala were hydrolysed to their des-Xaa-Ala derivatives by dipeptidyl-peptidase IV purified from human placenta. VIP with terminal His-Ser was not significantly degraded by the peptidase. The kinetics of the hydrolysis of GIP, GLP-1(7–36)amide and PHM were analyzed in detail. For these peptides Km values of 4–34 μM and Vmax values of 0.6–3.8 μmol · min−1· mg protein−1 were determined for the purified peptidase which should allow their enzymic degradation also at physiological, nanomolar concentrations. When human serum was incubated with GIP or GLP-1(7–36)amide the same fragments as with the purified dipeptidyl-peptidase IV, namely the des-Xaa-Ala peptides and Tyr-Ala in the case of GIP or His-Ala in the case of GLP-1(7–36)amide, were identified as the main degradation products of these peptide hormones. Incorporation of inhibitors specific for dipeptidylpeptidase IV, 1 mM Lys-pyrrolidide or 0.1 mM diprotin A (Ile-Pro-Ilc), completely abolished the production of these fragments by serum. It is concluded that dipeptidyl-peptidase IV initiates the metabolism of GIP and GLP-1(7–36)amide in human serum. Since an intact N-terminus is obligate for the biological activity of the members of the glucagon/VIP peptide family [e. g. GIP(3–42) is known to be inactive to release insulin in the presence of glucose as does intact GIP], dipeptidyl-peptidase-IV action inactivates these peptide hormones. The relevance of this finding for their inactivation and their determination by immunoassays is discussed.

Abbreviations
DPP IV

dipeptidyl-peptidase IV

GIP

gastric inhibitory polypeptide or glucose-dependent insulinotropic polypeptide

GLP-1(7–36)amide

glucagon-like peptide-1(7–36)amide or insulinotropin or preproglucagon(78–107)amide

GLP-2

glucagon like peptide-2 or preproglucagon(126–159)

GRF

growth-hormone-releasing factor/hormone

PHI

peptide histidine isoleucine

PHM

peptide histidine methionine

VIP

vasoactive intestinal peptide

PACAP

pituitary adenylate-cyclase-activating polypeptide

Enzyme
 

Dipeptidyl peptidase IV (EC 3.4.14.5)

REFERENCES

  1. Top of page
  2. Abstract
  3. REFERENCES
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