Greater circulating DPP4 activity is associated with impaired flow-mediated dilatation in adults with type 2 diabetes mellitus

Publication date: Available online 23 July 2019Source: Nutrition, Metabolism and Cardiovascular DiseasesAuthor(s): Barchetta I, Ciccarelli G, Barone E, Cimini FA, Ceccarelli V, Bertoccini L, Sentinelli F, Tramutola A, Del Ben M, Angelico F, Baroni MG, Lenzi A, Cavallo MGAbstractBackgroundDipeptidyl peptidase 4 (DPP4) is a key enzyme involved in the regulation of the incretin system exerted by cleaving the glucagon-like peptide 1 (GLP-1); the blockage of DPP4, exerted by the antidiabetic agents DPP4-inhibitors (DPP4-I), results in greater GLP-1 concentration and improved glycaemic control. DPP4 acts also as a pro-inflammatory molecule and mediates vascular damage in experimental models. The relationship between DPP4 activity and endothelial function in diabetes has not been explored yet. Aim of this study was to investigate systemic plasma DPP4 activity in relation to endothelial function in patients with type 2 diabetes mellitus (T2DM).Methods and ResultsSixty-two T2DM individuals were recruited in our Diabetes outpatient clinics, Sapienza University, Rome, Italy. All participants underwent complete clinical work-up; endothelial function was evaluated by flow-mediated dilatation (FMD) test; plasma DPP4 activity was assessed by measuring the 7-amino-4-methylcoumarin (AMC) cleavage rate from the synthetic substrate H-glycyl-prolyl-AMC and compared with DPP4 activity measured in sixty-two age-, sex-, BMI-matched non-diabetic subjects.Patients with T2DM had significantly higher D...
Source: Nutrition, Metabolism and Cardiovascular Diseases - Category: Nutrition Source Type: research

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AbstractType 2 diabetes mellitus (T2DM) is a heterogeneous condition that is related to both defective insulin secretion and peripheral insulin resistance. Beta cells are the major organ for secreting insulin hence, it is important to maintain an adequate beta-cell mass in response to various changes. Insulin resistance is a major cause of T2DM leads to elevated free fatty acid (FFA) levels which increases beta-cell mass and insulin secretion to compensate for insulin insensitivity. Chronic increase of plasma FFA levels results in disturbances in lipid metabolism, which contributes to decreased beta-cell function and lipot...
Source: Journal of Diabetes and Metabolic Disorders - Category: Endocrinology Source Type: research
Abstract Dipeptidyl peptidase-4 (DPP-4) inhibitors or gliptins belong to the class of incretin mimetics, one important group of antidiabetic medications. These drugs were available in the market for management of type 2 diabetes mellitus (T2DM) over a decade. Sitagliptin, linagliptin, vildagliptin, saxagliptin and alogliptin are the common drugs from gliptin family widely available globally, whilst anagliptin, gemigliptin and teneliptin are used mainly in the Asian countries. The glycemic control conferred by gliptins varies among individual molecules with an average reduction of glycated hemoglobin (HbA1c) rangin...
Source: Current Drug Safety - Category: Drugs & Pharmacology Authors: Tags: Curr Drug Saf Source Type: research
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors are so called “incretin-based therapies” (IBTs) that represent innovative therapeutic approaches and are commonly used in clinical practice for the treatment of type 2 diabetes mellitus (T2DM). The cardiovascular outcome trials (CVOTs) have provided useful information that has helped to shape changes in clini cal practice guidelines for the management of T2DM. At the same time, the mechanisms that may explain the nonglycemic and cardiovascular (CV) benefits of these medications are still being explored.
Source: Metabolism - Clinical and Experimental - Category: Biomedical Science Authors: Source Type: research
AbstractPrevious studies have demonstrated that individuals with type 2 diabetes mellitus (T2DM) have a two- to fourfold propensity to develop cardiovascular disease (CVD) than nondiabetic population, making CVD a major cause of death and disability among people with T2DM. The present treatment options for management of diabetes propose the earlier and more frequent use of new antidiabetic drugs that could control hyperglycaemia and reduce the risk of cardiovascular events. Findings from basic and clinical studies pointed out DPP-4 inhibitors as potentially novel pharmacological tools for cardioprotection. There is a growi...
Source: Heart Failure Reviews - Category: Cardiology Source Type: research
Abstract Obesity has become a global health problem. Lifestyle modification and medical treatment only appear to yield short-term weight loss. Roux-en-Y gastric bypass (RYGB) is the most popular bariatric procedure, and it sustains weight reduction and results in the remission of obesity-associated comorbidities for obese individuals. However, patients who undergo this surgery may develop hypoglycemia. To date, the diagnosis is challenging and the prevalence of post-RYGB hypoglycemia (PRH) is unclear. RYGB alters the anatomy of the upper gastrointestinal tract and has a combined effect of caloric intake restrictio...
Source: Chinese Medical Journal - Category: General Medicine Authors: Tags: Chin Med J (Engl) Source Type: research
Incretin hormones glucagon ‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP) play a major role in regulation of postprandial glucose and the development of type 2 diabetes mellitus. The incretins are rapidly metabolized, primarily by the enzyme dipeptidyl‐peptidase 4 (DPP4), and the neut ral endopeptidase (NEP), although the exact metabolization pathways are unknown. We developed a physiologically‐based (PB) quantitative systems pharmacology model of GLP‐1 and GIP and their metabolites that describes the secretion of the incretins in response to intraduodenal glucose infusions a n...
Source: CPT: Pharmacometrics and Systems Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Article Source Type: research
The dipeptidyl peptidase-4 inhibitors (DPP-4is), which belong to the class of incretin-based medications, are recommended as second or third-line therapies in guidelines for the management of type 2 diabetes mellitus. They have a favorable drug tolerability and safety profile compared to other glucose-lowering agents.
Source: Metabolism - Clinical and Experimental - Category: Biomedical Science Authors: Source Type: research
The dipeptidyl peptidase-4 inhibitors (DPP-4is), which belong to the class of incretin-based medications, are recommended as second or third-line therapies in guidelines for the management of type 2 diabetes mellitus. They have a favorable drug tolerability and safety profile compared to other glucose-lowering agents.
Source: Metabolism - Clinical and Experimental - Category: Biomedical Science Authors: Tags: Articles from the Incretin Hormones and Incretin-based Glucose-lowering Medications Special Issue, Edited by Michael Nauck, Manfredi Rizzo and Christos Mantzoros Source Type: research
Cardiovascular disease (CVD) is a major contributor to the morbidity and mortality associated with type 2 diabetes mellitus (T2DM). With T2DM growing in pandemic proportions, there will be profound healthcare implications of CVD in person with diabetes. The ideal drugs to improve outcomes in T2DM are those having antiglycemic efficacy in addition to cardiovascular (CV) safety, which has to be determined in appropriately designed CV outcome trials as mandated by regulatory agencies. Available evidence is largely supportive of metformin’s CV safety and potential CVD risk reduction effects, whereas sulfonylureas are eit...
Source: Cardiology in Review - Category: Cardiology Tags: Review Articles Source Type: research
Conclusions: In comparison to conventional ELISA, receptor-mediated bioassay reflects dynamic change of GIP polypeptide by DPP-4 inhibitor treatment in subjects with type 2 diabetes.
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
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