Disease relevance of Dpp4

• A novel consensus motif in fibronectin mediates dipeptidyl peptidase IV adhesion and metastasis [1].
• METHODS: Hepatocytes were transplanted via spleen from either F344 rats into syngeneic recipients deficient in dipeptidyl peptidase IV or from transgenic hepatitis B surface antigen-producing G26 mice with hepatitis B virus into nontransgenic congeneic recipients [2].
• Role of dipeptidyl peptidase IV (gp 108) in passive Heymann nephritis. Use of dipeptidyl peptidase IV-deficient rats [3].
• Injection of antibodies to renal tubular membrane (Fx1A) into Lewis rats induces granular deposits of IgG in glomeruli and proteinuria (passive Heymann nephritis, PHN), and similar lesions are also induced by antibody to one of the antigens in Fx1A, dipeptidyl peptidase IV (DPP IV, gp 108) [3].
• Long-term administration of specific DP IV inhibitors, so as to enhance circulating active GIP and GLP-1 levels, has been shown to improve glucose tolerance and beta-cell glucose responsiveness and to reduce hyperinsulinemia in the Vancouver diabetic fatty (VDF) rat model of type 2 diabetes [4].

High impact information on Dpp4

• Markers for Y chromosome, dipeptidyl peptidase IV enzyme, and L21-6 antigen were used to identify liver cells of bone marrow origin [5].
• Colocalization at the electron microscopic level showed that the apical protein, dipeptidyl peptidase IV, was in the same structures as aminopeptidase N, polymeric IgA receptor, or intravenously injected horseradish peroxidase [6].
• NH2-terminal sequencing established identity with dipeptidyl peptidase IV which had been reported to serve as a fibronectin-binding protein [7].
• To determine how epithelial cells establish a particular targeting phenotype, we studied the apical delivery of endogenous dipeptidyl peptidase IV (DPPIV) at early and late stages in the development of monolayers of a highly polarized epithelial cell line derived from Fischer rat thyroid (FRT) [8].
• Dipeptidyl peptidase IV (DPPIV) is a membrane glycoprotein with a type II orientation in the plasma membrane [9].

Chemical compound and disease context of Dpp4

• These results demonstrate that the combination therapy of metformin with DPPIV inhibitor leads to reduced food intake and body weight gain, most likely through the significant increase of plasma GLP-1 level [10].
• Therefore, a DPP-IV inhibitor in combination with glybenclamide or nateglinide may be a promising option for the treatment of type 2 diabetes, and particularly, for controlling postprandial hyperglycemia in the clinic [11].
• Massive proteinuria is induced in rats by administration of rabbit antibody to dipeptidyl peptidase IV (DPPIV, gp108), a glycoprotein present on glomerular cell membranes and in serum [12].
• Dipeptidyl peptidase IV in C6 rat glioma cell line differentiation [13].
• We conclude that severe glutathione depletion induces cholestasis by a retrieval of Mrp2, but not of DPPIV from the canalicular membrane [14].

Biological context of Dpp4

• Liraglutide, a Long-Acting Glucagon-Like Peptide-1 Analog, Reduces Body Weight and Food Intake in Obese Candy-Fed Rats, Whereas a Dipeptidyl Peptidase-IV Inhibitor, Vildagliptin, Does Not [15].
• Metabolic effects of the glucagon-like peptide-1 analog liraglutide and the dipeptidyl peptidase-IV inhibitor vildagliptin were compared in rats made obese by supplementary candy feeding [15].
• Insulin-dependent phosphorylation of DPP IV in liver. Evidence for a role of compartmentalized c-Src [16].
• Dipeptidyl peptidase IV (DPP IV, CD26, EC 3.4.14.5) serves as a model aimed at elucidating protein sorting signals [16].
• This paper describes the tissue distribution, purification and N-terminal amino acid sequence of the bile canalicular cell surface molecule dipeptidyl peptidase IV [17].

Anatomical context of Dpp4

• Following injection of the protein-tyrosine phosphatase inhibitor bpV(phen), DPP IV levels markedly decreased by 40% both in plasma membrane and G/E fractions [16].
• DPP IV was found phosphorylated after incubation of nonsolubilized G/E membranes with [gamma-32P]ATP [16].
• We identify here, by MS, several tyrosine-phosphorylated proteins in a rat liver Golgi/endosome (G/E) fraction including DPP IV [16].
• As shown in a cell-free translation system, the amino-terminal 34 amino acids of rat DPPIV are involved in translocating nascent polypeptide across the membrane of microsomes and in anchoring the translocated polypeptide in the microsomal membrane [9].
• cDNA cloning for a bile canaliculus domain-specific membrane glycoprotein of rat hepatocytes [18].

Associations of Dpp4 with chemical compounds

• DPP IV coimmunoprecipitated with the cellular tyrosine kinase Src (c-Src) with maximal association also observed after 2 min following insulin injection [16].
• Molecular dissection of the NH2-terminal signal/anchor sequence of rat dipeptidyl peptidase IV [9].
• Site-directed mutagenesis studies show that deletion of this cytoplasmic domain, excluding the amino-terminal initiating methionine, does not affect translocation of nascent DPPIV polypeptide, but does affect significantly anchoring of the translocated polypeptide in the microsomal membrane [9].
• Two forms of dipeptidyl peptidase IV (DPP) were purified from rat liver plasma membranes: a membrane form (mDPP) extracted with Triton X-100 and a soluble form (sDPP) prepared by treatment with papain [19].
• These observations suggest that DPPIV deficiency results in improved glucose tolerance and ameliorated insulin resistance owing to enhanced insulin release and inhibition of food intake as a result of high active GLP-1 levels [20].

Physical interactions of Dpp4

• Fibronectin appeared to bind DPP IV at a site distinct from its exopeptidase substrate recognition site since protease inhibitors such as competitive peptide substrates and phenylmethanesulphonyl fluoride enhanced binding, possibly as a result of an altered conformation of DPP IV [21].
• Approximately 60% of the dipeptidyl peptidase IV interacted with either one or both of the lectins while only 30% of the aminopeptidase N did so [22].
• Treatment of both enzymes with neuraminidase enhanced the binding of aminopeptidase to RCAI-Sepharose by 4-fold but did not alter the binding patterns of dipeptidyl peptidase IV [22].

Regulatory relationships of Dpp4

• The c-Src inhibitor PP2 inhibited DPP IV phosphorylation [16].
• It is concluded that DPP IV may be a primary inactivating enzyme of both GIP and tGLP-1 in vivo [23].

Other interactions of Dpp4

• The results suggest the presence of a yet to be characterized signalling mechanism whereby DPP IV has access to c-Src-containing signalling platforms [16].
• It is also found that the primary structure thus predicted has striking homology to that of gp 110, a bile canaliculus domain-specific membrane glycoprotein (Hong, W., and Doyle, D. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 7962-7966) [19].
• Identification of the bile canalicular cell surface molecule GP110 as the ectopeptidase dipeptidyl peptidase IV: an analysis by tissue distribution, purification and N-terminal amino acid sequence [17].
• Effect of neuropeptide Y on inflammatory paw edema in the rat: involvement of peripheral NPY Y1 and Y5 receptors and interaction with dipeptidyl-peptidase IV (CD26) [24].
• Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV [23].

Analytical, diagnostic and therapeutic context of Dpp4

• GOALS: In models of experimental cardiac allograft transplantation (HTx), we analyzed the role of CD26/DPP IV during organ rejection [25].
• CD26/DPP IV in experimental and clinical organ transplantation [25].
• METHODS: Wild-type (dipeptidyl peptidase IV [DPPIV(+)]) embryonic day (ED) 14 fetal liver cells underwent transplantation into DPPIV(-) mutant F344 rats to follow the fate and differentiation of transplanted cells [26].
• Rats with chimeric livers were generated by using the protocol of injecting hepatocytes from dipeptidyl peptidase IV (DPPIV)-positive donors into retrorsine-treated DPPIV-negative recipients subjected to partial hepatectomy [27].
• We used syngeneic and allogeneic cell transplantation assays based on F344 recipient rats lacking dipeptidyl peptidase IV enzyme activity to identify transplanted hepatocytes [28].

References