No abstract available.
Dipeptidyl-Peptidase IV Inhibitors ; Myocardial Infarction ; Cardiovascular Diseases ; Dipeptidyl Peptidase 4 ; Diabetes Mellitus, Type 2

Dipeptidyl peptidase-4 (DPP-4) is a protease that cleaves the peptides with alanine, praline, or other selective amino acids at the N-terminal penultimate position. The substrates of DPP-4 include many chemokines, colony-stimulating factors, and interleukins. Recent research has shown that DPP-4 can affect the hematopoietic stem and progenitor cells and transplantation by truncating the granulocyte colony stimulating factor. However, its regulatory effect on DPP-4 and most peptides truncation are still unknown. This review summarizes the recent advances in the DPP-4 research.
Dipeptidyl Peptidase 4 ; physiology ; Hematopoiesis ; Hematopoietic Stem Cell Transplantation ; Humans

Type 2 diabetes mellitus (T2DM) is a progressive disorder caused by a combination of insulin resistance and betacell dysfunction. The role of new hormones and systems in maintaining blood glucose homeostasis has recently been recognized. This recognition has led to the development of several novel classes of medications, including the incretin mimetic agents (glucagon like polypeptide-1 analogs and dipeptidyl peptidase IV inhibitors), the amylin analog and the endocannabinoid-1 receptor blocker. This review looks at these new agents in terms of their mode of action, pharmacokinetics and use in clinical practice. The new agents offer treatment options in select adult patients now, however, the efficacy and the safety has to be evaluated thoroughly by long term studies before the application to pediatric patients.
Adult ; Blood Glucose ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Dipeptidyl Peptidase 4 ; Dipeptidyl-Peptidase IV Inhibitors ; Glucagon-Like Peptides ; Homeostasis ; Humans ; Incretins ; Insulin Resistance ; Islet Amyloid Polypeptide

BACKGROUND: The aims of this study are to investigate the glycemic efficacy and predictive parameters of vildagliptin therapy in Korean subjects with type 2 diabetes. METHODS: In this retrospective study, we retrieved data for subjects who were on twice-daily 50 mg vildagliptin for at least 6 months, and classified the subjects into five treatment groups. In three of the groups, we added vildagliptin to their existing medication regimen; in the other two groups, we replaced one of their existing medications with vildagliptin. We then analyzed the changes in glucose parameters and clinical characteristics. RESULTS: Ultimately, 327 subjects were analyzed in this study. Vildagliptin significantly improved hemoglobin A1c (HbA1c) levels over 6 months. The changes in HbA1c levels (DeltaHbA1c) at month 6 were -2.24% (P=0.000), -0.77% (P=0.000), -0.80% (P=0.001), -0.61% (P=0.000), and -0.34% (P=0.025) for groups 1, 2, 3, 4, and 5, respectively, with significance. We also found significant decrements in fasting plasma glucose levels in groups 1, 2, 3, and 4 (P<0.05). Of the variables, initial HbA1c levels (P=0.032) and history of sulfonylurea use (P=0.026) were independently associated with responsiveness to vildagliptin treatment. CONCLUSION: Vildagliptin was effective when it was used in subjects with poor glycemic control. It controlled fasting plasma glucose levels as well as sulfonylurea treatment in Korean type 2 diabetic subjects.
Adamantane ; Diabetes Mellitus ; Dipeptidyl Peptidase 4 ; Fasting ; Glucose ; Hemoglobins ; Nitriles ; Plasma ; Pyrrolidines ; Retrospective Studies

OBJECTIVE: To investigate the gene mutation and genotype distribution of thalassemia in the population of childbearing age in Chongzuo area of Guangxi. METHODS: Six α-thalassemia and 17 β-thalassemia gene mutations common in Chinese were detected by gap-polymerase chain reaction (gap-PCR) combined with agarose gel eletrophoresis and reserve dot bolt hybridization in 29 266 cases of child-bearing age suspected of thalassemia. RESULTS: A total of 19 128 (65.36%) cases were identified with thalassemia. The detection rate of α-thalassemia, β-thalassemia and α-combining β-thalassemia was 45.25% (13 242/29 266), 15.47% (4 526/29 266) and 4.65% (1 360/29 266), respectively. A total carrying rate of 8 kinds of α-thalassemia gene mutations was 26.74% (15 649/58 532), including 12.51% for --^SEA, followed by 5.70% for -α^3.7, and 0.24% for --^Thai. Among 32 α-thalassemia genotypes, the most common five were --^SEA/αα, -α^3.7/αα, α^CSα/αα, -α^4.2/αα and α^WSα/αα, accounting for 47.27%, 18.31%, 8.56%, 8.52% and 7.91%, respectively, as well as 0.97% for --^Thai/αα. A total carrying rate of 13 kinds of β-thalassemia gene mutations was 10.07% (5 897/58 532), including 3.63% for CD41-42, followed by 2.55% for CD17, and 0.003% for -50 (G>A). Among 17 β-thalassemia genotypes, the most common six were CD41-42/N, CD17/N, CD71-72/N, CD26/N, 28/N and IVSI-1/N, accounting for 36.15%, 25.81%, 9.43%, 8.18%, 8.09% and 7.75%. The homozygous genotype CD26/CD26 [hemoglobin (Hb): 121 g/L] and -28/-28 (Hb: 56 g/L) were respectively detected in one case, and double heterozygous genotype were detected in 5 cases, including 3 cases of CD41-42/CD26 (Hb: 41 g/L, 51 g/L, 63 g/L, respectively), 1 case of -28/IVSI-1 (Hb: 53 g/L), and 1 case of CD71-72/CD26 (Hb: 89 g/L), in which patients with moderate or severe anemia had a history of blood transfusion. Among 104 α-combining β-thalassemia genotypes, the most common were --^SEA/αα, -α^3.7/αα combining CD41-42/N and --^SEA/αα combining CD17/N, accounting for 12.13%, 9.63% and 9.26%, respectively. In addition, 1 case of --^SEA/-α^3.7 combining -28/IVSI-1 (Hb: 83 g/L) and 1 case of -α^3.7/αα combining CD41-42/ CD41-42 (Hb: 110 g/L) were detected without history of blood transfusion, while 1 case of α^WSα/αα combining CD41-42/CD17 (Hb: 79 g/L) and 1 case of --^SEA/αα combining CD17/-28 (Hb: 46 g/L) were detected with history. CONCLUSIONS The detection rate of thalassemia genes is high and the mutations are diverse in the population of childbearing age in Chongzuo area of Guangxi. The common deletion genotype is --^SEA/αα in α-thalassemia and CD41-42/N in β-thalassemia, and deletion genotype --^Thai is not rare. There is a certain incidence of intermediate and severe β-thalassemia, and most patients require transfusion therapy. The results are beneficial for genetic consultation and intervention of thalassemia.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Dipeptidyl Peptidase 4/genetics* ; China/epidemiology* ; Genotype ; Mutation

BACKGROUND: Dipeptidyl peptidase 4/CD26 (DPP-4) is a widely expressed cell surface serine protease. DPP-4 inhibitors, one of common anti-diabetic agents play a protective role in bone metabolism in recent studies. A soluble form of DPP-4 is found in serum, and exhibits DPP-4 enzymatic activity. However, the physiological role of serum or soluble DPP-4 and its relationship with DPP-4 enzymatic function remain poorly understood. The aims of current study were to determine the association between serum DPP-4 activity and bone mineral density (BMD) in postmenopausal women. METHODS: We recruited data and serum samples from 124 consecutive healthy postmenopausal women aged >50 years. We divided study subjects into obese (body mass index [BMI] ≥25 kg/m2) and non-obese (BMI <25 kg/m2) postmenopausal women and examined the correlation between serum DPP-4 activity and clinical variables in each groups. RESULTS: A total of 124 postmenopausal women was enrolled, with a mean age of 59.9±7.1 years. The mean BMI of the study patients was 24.4±2.8 kg/m2. Regarding bone turnover markers, serum DPP-4 activity was positively correlated with serum calcium concentrations, intact parathyroid hormone, and serum C-telopeptide levels in all of the study subjects. However, there was no association between serum DPP-4 activity and BMD in the spine or femoral neck in all of the study subjects. Serum DPP-4 activity was negatively correlated (R=−0.288, P=0.038) with BMD of the spine in obese postmenopausal women. CONCLUSION: This study demonstrated for the first time that serum soluble DPP-4 activity was negatively correlated with BMD in obese postmenopausal women.
Biological Markers ; Bone Density* ; Calcium ; Dipeptidyl Peptidase 4 ; Female ; Femur Neck ; Humans ; Metabolism ; Parathyroid Hormone ; Postmenopause ; Serine Proteases ; Spine

Dipeptidyl peptidase 4 (DPP4) inhibitors have been touted as promising antihyperglycemic agents due to their beneficial effects on glycemia without inducing hypoglycemia or body weight gain and their good tolerability. Beyond their glucose-lowering effects, numerous clinical trials and experimental studies have suggested that DPP4 inhibitors may exert cardioprotective effects through their pleiotropic actions via glucagon-like peptide 1-dependent mechanisms or involving other substrates. Since 2008, regulatory agencies have required an assessment of cardiovascular disease (CVD) safety for the approval of all new anti-hyperglycemic agents, including incretin-based therapies. Three large prospective DPP4 inhibitor trials with cardiovascular (CV) outcomes have recently been published. According to the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR-TIMI 53) and EXamination of cArdiovascular outcoMes with alogliptIN versus standard of carE in patients with type 2 diabetes mellitus and acute coronary syndrome (EXAMINE) trials, DPP4 inhibitors, including saxagliptin and alogliptin, did not appear to increase the risk of CV events in patients with type 2 diabetes and established CVD or high risk factors. Unexpectedly, saxagliptin significantly increased the risk of hospitalization for heart failure by 27%, a finding that has not been explained and that requires further exploration. More recently, the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) trial demonstrated the CV safety of sitagliptin, including assessments of the primary composite CV endpoint and hospitalization for heart failure in patients with type 2 diabetes and established CVD. The CV outcomes of an ongoing linagliptin trial are expected to provide new evidence about the CV effects of a DPP4-inhibitor in patients with type 2 diabetes.
Acute Coronary Syndrome ; Body Weight ; Cardiovascular Diseases* ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Dipeptidyl Peptidase 4* ; Dipeptidyl-Peptidase IV Inhibitors* ; Heart Failure ; Hospitalization ; Humans ; Hypoglycemia ; Hypoglycemic Agents ; Prospective Studies ; Risk Factors ; Standard of Care ; Linagliptin ; Sitagliptin Phosphate

BACKGROUND: Glycemic variability is associated with the development of diabetic complications through the activation of oxidative stress. This study aimed to evaluate the effects of a dipeptidyl peptidase 4 inhibitor, vildagliptin, or a thiazolidinedione, pioglitazone, on glycemic variability and oxidative stress in patients with type 2 diabetes. METHODS: In this open label, randomised, active-controlled, pilot trial, individuals who were inadequately controlled with metformin monotherapy were assigned to either vildagliptin (50 mg twice daily, n=17) or pioglitazone (15 mg once daily, n=14) treatment groups for 16 weeks. Glycemic variability was assessed by calculating the mean amplitude of glycemic excursions (MAGE), which was obtained from continuous glucose monitoring. Urinary 8-iso prostaglandin F₂α, serum oxidised low density lipoprotein, and high-sensitivity C-reactive protein were used as markers of oxidative stress or inflammation. RESULTS: Both vildagliptin and pioglitazone significantly reduced glycated hemoglobin and mean plasma glucose levels during the 16-week treatment. Vildagliptin also significantly reduced the MAGE (from 93.8±38.0 to 70.8±19.2 mg/dL, P=0.046), and mean standard deviation of 24 hours glucose (from 38±17.3 to 27.7±6.9, P=0.026); however, pioglitazone did not, although the magnitude of decline was similar in both groups. Markers of oxidative stress or inflammation including urinary 8-iso prostaglandin F₂α did not change after treatment in both groups. CONCLUSION: In this 16-week treatment trial, vildagliptin, but not pioglitazone, reduced glycemic variability in individuals with type 2 diabetes who was inadequately controlled with metformin monotherapy, although a reduction of oxidative stress markers was not observed.
Blood Glucose ; C-Reactive Protein ; Diabetes Complications ; Diabetes Mellitus, Type 2 ; Dipeptidyl Peptidase 4 ; Dipeptidyl-Peptidase IV Inhibitors ; Glucose ; Hemoglobin A, Glycosylated ; Humans ; Inflammation ; Lipoproteins ; Metformin* ; Oxidative Stress* ; Pilot Projects* ; Thiazolidinediones

Despite strict pre- and post-transplantation screening, the incidence of new-onset diabetes after transplantation (NODAT) remains as high as 60%. This complication affects the risk of cardiovascular events and patient and graft survival rates. Thus, reducing the impact of NODAT could improve overall transplant success. The pathogenesis of NODAT is multifactorial, and both modifiable and nonmodifiable risk factors have been implicated. Monitoring and controlling the blood glucose profile, implementing multidisciplinary care, performing lifestyle modifications, using a modified immunosuppressive regimen, administering anti-metabolite agents, and taking a conventional antidiabetic approach may diminish the incidence of NODAT. In addition to these preventive strategies, inhibition of dipeptidyl peptidase-4 (DPP4) by the gliptin family of drugs has recently gained considerable interest as therapy for type 2 diabetes mellitus and NODAT. This review focuses on the role of DPP4 inhibitors and discusses recent literature regarding management of NODAT.
Animals ; Blood Glucose/drug effects/metabolism ; Diabetes Mellitus/diagnosis/*drug therapy/enzymology/etiology ; Dipeptidyl Peptidase 4/*metabolism ; Dipeptidyl-Peptidase IV Inhibitors/*therapeutic use ; Humans ; Organ Transplantation/*adverse effects ; Risk Assessment ; Risk Factors ; Treatment Outcome

Dipeptidylpeptidase (DPP) 4, also known as CD26, is an enzyme present on the surface of a number of different cell types. It is also found within cells and as a soluble protein in body fluids. It can specifically truncate proteins at the penultimate N-terminus residue for some amino acids, such as alanine, proline, serine, and perhaps others. DPP4 has been implicated in regulating the in vitro and in vivo functional activities of a number of hematopoietically active molecules, and this information, along with that on inhibition of DPP4, has been studied in efforts to enhance hematopoietic cell transplantation (HCT), hematopoiesis after stress in mouse models, and in the clinical setting of single-unit cord blood (CB) HCT. This article reviews the current status of this compound's effects on regulatory proteins, the field of CB HCT, a potential role for modulating DPP4 activity in enhancing single-unit CB HCT in adults, and future aspects in context of other cellular therapies and the area of regenerative medicine.
Animals ; *Cord Blood Stem Cell Transplantation ; Dipeptidyl Peptidase 4/*metabolism ; Dipeptidyl-Peptidase IV Inhibitors/*therapeutic use ; Hematopoiesis/*drug effects ; Hematopoietic Stem Cells/*drug effects/enzymology ; Humans ; Regenerative Medicine/*methods ; Signal Transduction/drug effects