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CD26: A Prognostic Marker of Acute Lymphoblastic Leukemia in Children in the Post Remission Induction Phase

Mehde AA, Yusof F, Adel Mehdi W, Zainulabdeen JA

Asian Pac J Cancer Prev, 2015;16(12):5059-62.
PMID: 26163641

BACKGROUND: ALL is an irredeemable disease due to the resistance to treatment. There are several influences which are involved in such resistance to chemotherapy, including oxidative stress as a result of the generation of reactive oxygen species (ROS) and presence of hypodiploid cells. Cluster of differentiation 26 (CD26), also known as dipeptidyl peptidase-4, is a 110 kDa, multifunctional, membrane-bound glycoprotein.
AIM AND OBJECTIVES: The aim of this study was to evaluate the clinical significance of serum CD26 in patients with acute lymphoblastic leukaemia patients in the post remission induction phase, as well as the relationship between CD26 activity and the oxidative stress status.
MATERIALS AND METHODS: CD26, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI), in addition to activity of related enzymes myeloperoxidase, glutathione- s-transferase and xanthine oxidase, were analysed in sixty children with acute lymphoblastic leukaemia in the post remission induction phase.
RESULTS: The study showed significant elevation in CD26, TOS and OSI levels in patients with acute lymphoblastic leukaemia in the post remission induction phase in comparison to healthy control samples. In contrast, myeloperoxidase, glutathione-s-transferase and xanthine oxidase activities were decreased significantly. A significant correlation between CD26 concentration and some oxidative stress parameters was evident in ALL patients.
CONCLUSIONS: Serum levels of CD26 appear to be useful as a new biomarker of oxidative stress in children with acute lymphoblastic leukaemia in the post remission induction phase, and levels of antioxidants must be regularly estimated during the treatment of children with ALL.

Matched MeSH terms: Dipeptidyl Peptidase 4/metabolism*
Cardiovascular pleiotropic actions of DPP-4 inhibitors: a step at the cutting edge in understanding their additional therapeutic potentials

Balakumar P, Dhanaraj SA

Cell Signal, 2013 Sep;25(9):1799-803.
PMID: 23707531 DOI: 10.1016/j.cellsig.2013.05.009

Dipeptidyl peptidase 4 (DPP-4) is a serine protease enzyme expressed widely in many tissues, including the cardiovascular system. The incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from the small intestine into the vasculature during a meal, and these incretins have a potential to release insulin from pancreatic beta cells of islets of Langerhans, affording a glucose-lowering action. However, both incretins are hurriedly degraded by the DPP-4. Inhibitors of DPP-4, therefore, enhance the bioavailability of GLP-1 and GIP, and thus have been approved for better glycemic management in patients afflicted with type 2 diabetes mellitus (T2DM). Five different DPP-4 inhibitors, often called as 'gliptins', namely sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin have been approved hitherto for clinical use. These drugs are used along with diet and exercise to lower blood sugar in diabetic subjects. T2DM is intricately related with an increased risk of cardiovascular disease. Growing body of evidence suggests that gliptins, in addition to their persuasive anti-diabetic action, have a beneficial pleiotropic action on the heart and vessels. In view of the fact of cardiovascular disease susceptibility of patients afflicted with T2DM, gliptins might offer additional therapeutic benefits in treating diabetic cardiovascular complications. Exploring further the cardiovascular pleiotropic potentials of gliptins might open a panorama in impeccably employing these agents for the dual management of T2DM and T2DM-associated perilous cardiovascular complications. This review will shed lights on the newly identified beneficial pleiotropic actions of gliptins on the cardiovascular system.

Matched MeSH terms: Dipeptidyl Peptidase 4/metabolism
Molecular basis of the anti-diabetic properties of camel milk through profiling of its bioactive peptides on dipeptidyl peptidase IV (DPP-IV) and insulin receptor activity

Ashraf A, Mudgil P, Palakkott A, Iratni R, Gan CY, Maqsood S, et al.

J Dairy Sci, 2021 Jan;104(1):61-77.
PMID: 33162074 DOI: 10.3168/jds.2020-18627

The molecular basis of the anti-diabetic properties of camel milk reported in many studies and the exact active agent are still elusive. Recent studies have reported effects of camel whey proteins (CWP) and their hydrolysates (CWPH) on the activities of dipeptidyl peptidase IV (DPP-IV) and the human insulin receptor (hIR). In this study, CWPH were generated, screened for DPP-IV binding in silico and inhibitory activity in vitro, and processed for peptide identification. Furthermore, pharmacological action of intact CWP and their selected hydrolysates on hIR activity and signaling and on glucose uptake were investigated in cell lines. Results showed inhibition of DPP-IV by CWP and CWPH and their positive action on hIR activation and glucose uptake. Interestingly, the combination of CWP or CWPH with insulin revealed a positive allosteric modulation of hIR that was drastically reduced by the competitive hIR antagonist. Our data reveal for the first time the profiling and pharmacological actions of CWP and their derived peptides fractions on hIR and their pathways involved in glucose homeostasis. This sheds more light on the anti-diabetic properties of camel milk by providing the molecular basis for the potential use of camel milk in the management of diabetes.

Matched MeSH terms: Dipeptidyl Peptidase 4/metabolism*
Comparative studies of dipeptidyl peptidase 4 inhibitor vs sulphonylurea among Muslim Type 2 diabetes patients who fast in the month of Ramadan: A systematic review and meta-analysis

Loh HH, Yee A, Loh HS, Sukor N, Kamaruddin NA

Prim Care Diabetes, 2016 Jun;10(3):210-9.
PMID: 26392074 DOI: 10.1016/j.pcd.2015.09.001

AIM: To systematically review the literature to compare the use of DPP4 inhibitors vs sulphonylurea in type 2 diabetic Muslim patients who fast in Ramadan, with regards to its safety, tolerability, glycemic control, and body weight changes.
METHODS: All English-language medical literature published from inception till October 2014 which met the inclusion criteria were reviewed and analyzed.
RESULTS: A total of nine papers were included, reviewed and analyzed. The total sample size was 4276 patients. All studies used either of the two DPP4 inhibitors - Vildagliptin or Sitagliptin, vs sulphonylurea or meglitinides. Patients receiving DPP4 inhibitors were less likely to develop symptomatic hypoglycemia (risk ratio 0.46; 95% CI, 0.30-0.70), confirmed hypoglycemia (risk ratio 0.36; 95% CI, 0.21-0.64) and severe hypoglycemia (risk ratio 0.22; 95% CI, 0.10-0.53) compared with patients on sulphonylureas. There was no statistically significant difference in HbA1C changes comparing Vildagliptin and sulphonylurea.
CONCLUSION: DPP4 inhibitor is a safer alternative to sulphonylurea in Muslim patients with type 2 diabetes mellitus who fast during the month of Ramadan as it is associated with lower risk of symptomatic, confirmed and severe hypoglycemia, with efficacy comparable to sulphonylurea.

Matched MeSH terms: Dipeptidyl Peptidase 4/metabolism*
Albiglutide: Is a better hope against diabetes mellitus?

Sharma AK, Thanikachalam PV, Rajput SK

Biomed Pharmacother, 2016 Feb;77:120-8.
PMID: 26796275 DOI: 10.1016/j.biopha.2015.12.015

Type-2 diabetes mellitus (T2DM) is the chronic metabolic disorder which provokes several pitfall signalling. Though, a series of anti-diabetic drugs are available in the market but T2DM is still a huge burden on the developed and developing countries. Numerous studies and survey predict the associated baleful circumstances in near future due to incessant increase in this insidious disorder. The novelty of recent explored anti-diabetic drugs including glitazone, glitazaar and gliflozines seems to be vanished due to their associated toxic side effects. Brown and Dryburgh (1970) isolated an intestinal amino acid known as gastric inhibitory peptide (GIP) which had insulinotropic activity. Subsequently in 1985, another incretin glucagon likes peptide 1 (GLP-1) having potent insulinotropic properties was discovered by Schmidt and his co-workers. On the basis of results' obtained by Phase III Harmony program FDA approved (14 April, 2014) new GLP-1 agonist 'Albiglutide (ALB)', in addition to exiting components Exenatide (Eli Lilly, 2005) and Liraglutide (Novo Nordisk, 2010). ALB stimulates the release of protein kinase A (PKA) via different mechanisms which ultimately leads to increase in intracellular Ca(2+) levels. This increased intracellular Ca(2+) releases insulin vesicle from β-cells. In-addition, ALB being resistant to degradation by dipeptidyl peptidase-4 (DPP-4) and has longer half life. DPP-4 can significantly degrade the level of GLP-1 agonist by hydrolysis. In spite of potent anti-hypergycemic activity, ALB has pleiotropic action of improving cardiovascular physiology. In light of these viewpoints we reveal the individual pharmacological profile of ALB and the critical analyse about its future perspective in present review.

Matched MeSH terms: Dipeptidyl Peptidase 4/metabolism
Fulltext Inhibitory evaluation of Curculigo latifolia on α-glucosidase, DPP (IV) and in vitro studies in antidiabetic with molecular docking relevance to type 2 diabetes mellitus

Zabidi NA, Ishak NA, Hamid M, Ashari SE, Mohammad Latif MA

J Enzyme Inhib Med Chem, 2021 Dec;36(1):109-121.
PMID: 33249946 DOI: 10.1080/14756366.2020.1844680

The inhibition of α-glucosidase and DPP enzymes capable of effectively reducing blood glucose level in the management of type 2 diabetes. The purpose of the present study is to evaluate the inhibitory potential of α-glucosidase and DPP (IV) activity including with the 2-NBDG uptake assay and insulin secretion activities through in vitro studies. The selected of active compounds obtained from the screening of compounds by LC-MS were docked with the targeted enzyme that involved in the mechanism of T2DM. From the results, root extracts displayed a better promising outcome in α-glucosidase (IC50 2.72 ± 0.32) as compared with the fruit extracts (IC50 3.87 ± 0.32). Besides, root extracts also displayed a better activity in the inhibition of DPP (IV), enhance insulin secretion and glucose uptake activity. Molecular docking results revealing that phlorizin binds strongly with α-glucosidase, DPP (IV) and Insulin receptor (IR) enzymes with achieving the lowest binding energy value. The present work suggests several of the compounds have the potential that contribute towards inhibiting α-glucosidase and DPP (IV) and thus effective in lowering post-prandial hyperglycaemia.

Matched MeSH terms: Dipeptidyl Peptidase 4/metabolism