To determine the importance of selective DPP-IV inhibition for the treatment of diabetes, we tested selective inhibitors of DPP-IV, DPP8/DPP9, or QPP in 2-week rat toxicity studies and in acute dog tolerability studies.
Daily administration of DPP-IV inhibitor to the experimental diabetes model at doses of 10mg/kg for 32 weeks protected nerve fiber loss compared with untreated rats as follows (IENF/mm): normal (9.89+/-0.34), diabetes mellitus (DM) (8.42+/-0.28), DM with 0.3mg/kg DPP-IV inhibitor (9.88+/-0.38), and DM with 10mg/kg DPP-IV inhibitor (10.36+/-0.32) (p<0.05).
Because atherosclerosis-related cardiovascular diseases are the major complications of diabetes, it is important to determine the effect of DPP-4 inhibitors on atherosclerosis.
When the angiotensin-converting enzyme is inhibited, bradykinin metabolism is dependent on degradation by neutral endopeptidase, dipeptidyl peptidase IV, and aminopeptidase P. When these enzymes are inhibited, as in treatment of diabetes or in transplant recipients, the incidence of angioedema increases significantly.
Using the Metabochip, we identified three novel genetic loci with large effects (30-40%) on GLP-1-stimulated insulin secretion during hyperglycemic clamps in nondiabetic Caucasian individuals (TMEM114; CHST3 and CTRB1/2; n = 232; all P ≤ 8.8 × 10(-7)). rs7202877 near CTRB1/2, a known diabetes risk locus, also associated with an absolute 0.51 ± 0.16% (5.6 ± 1.7 mmol/mol) lower A1C response to DPP-4 inhibitor treatment in G-allele carriers, but there was no effect on GLP-1 RA treatment in type 2 diabetic patients (n = 527).
The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin is an attractive therapy for diabetes, as it increases insulin release and may preserve β-cell mass.
CD26/DPPIV is a widely distributed multifunctional integral membrane and secreted protein that is defined as early predictive biomarker in HIV, cancer and autoimmunity diseases like diabetes and multiple sclerosis.
This retrospective study of EMR data covering up to 30 months after CANA approval (March 2013) suggests that patients initiated on CANA were more likely to reach HbA1c, systolic BP, and weight loss objectives specified by general diabetes care guidelines than patients initiated on DPP-4 inhibitors.
Our results suggested that the protein hydrolysate from Antarctic krill can be considered as a promising natural source of DPP-IV inhibitory peptides in the management of diabetes.
Furthermore, this formulation effectively controlled blood glucose and significantly decreased the body weight of mice, suggesting that MSN-HCD exerts natural DPP4 inhibitor as a potential clinical drug for the treatment of diabetes.
Inhibition of the enzymatic function and genetic deletion of DPP4 is associated with tremendous benefits to the heart, vasculature, adipose tissue, and the kidney in rodent models of obesity, diabetes and hypertension, and associated complications.
The LCK participants experienced larger reductions in diabetes-related medication use; of participants who took sulfonylureas or dipeptidyl peptidase-4 inhibitors at baseline, 6/10 in the LCK group discontinued these medications compared with 0/6 in the MCCR group (p = .005).
A novel multi-epitope vaccine based on Dipeptidyl Peptidase 4 prevents streptozotocin-induced diabetes by producing anti-DPP4 antibody and immunomodulatory effect in C57BL/6J mice.
Non-obese Asian Indian patients with T2DM and on metformin therapy have significantly higher circulating plasma DPP4 levels as compared to non-obese non-diabetic controls, and these levels correlate with fasting insulin and LDL-C levels, upper limb subcutaneous adipose tissue, intra-abdominal adiposity and presence of diabetes.
Dipeptidyl peptidase 4 inhibitors are used worldwide in the management of diabetes, but their role in the prevention or treatment of cardiovascular disorders has yet to be defined.