Abstract：
OBJECTIVE:Dipeptidyl peptidase-4 (DPP-4) is responsible for degradation of glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP), the endogenous incretins that stimulate glucose-dependent insulin secretion. The objective was to evaluate preclinical profile of a novel DPP-4 inhibitor ZYDPLA1. METHODS:In vitro inhibition potency and selectivity were assessed using recombinant enzymes and/or plasma. In vivo efficacy was determined in oral glucose tolerance test or mixed meal tolerance test in C57BL/6J mice, db/db mice and Zucker fatty rats. Pharmacokinetics/pharmacodynamics was studied in mice, rats, dogs, and non-human primates. RESULTS:ZYDPLA1 is a potent, competitive and long acting inhibitor of DPP-4 (Ki 0.0027 μM; Koff 2.3 × 10(-4 ) s(-1) ). ZYDPLA1 was more than 7000-fold selective for recombinant DPP-4 relative to DPP-8 and DPP-9, and more than 60 000-fold selective relative to fibroblast activation protein (FAP) in vitro. DPP-4 inhibition was comparable across species. In vivo, oral ZYDPLA1 elevated circulating GLP-1 and insulin levels in mice and rats and showed dose-dependent anti-hyperglycemic effect. Anti-hyperglycemic effect was also observed in db/db mice and Zucker fatty rats. ZYDPLA1 showed low clearance, large volume of distribution, and a long half-life with excellent oral bioavailability in all species. It significantly inhibited plasma DPP-4 activity in mice and rats for more than 48 h, and for up to 168 h in dogs and non-human primates. Allometric scaling predicted a half-life in humans of 53 to 166 h. CONCLUSION:ZYDPLA1 is a potent, selective, long-acting oral DPP-4 inhibitor with potential to become once-a-week therapy for treatment of type 2 diabetes mellitus.
journal_name
J Diabetesjournal_title
Journal of diabetesauthors
Jain MR,Joharapurkar AA,Bahekar RH,Patel H,Jadav P,Kshirsagar SG,Patel VJ,Patel KN,Ramanathan VK,Patel PR,Desai RCdoi
10.1111/1753-0407.12233subject
Has Abstractpub_date
2015-09-01 00:00:00pages
708-17issue
5eissn
1753-0393issn
1753-0407journal_volume
7pub_type
杂志文章abstract：:Observations from clinical studies suggest that low serum levels of testosterone in men are often associated with obesity, insulin resistance, and metabolic compromise. Indeed, the clinical symptoms of late-onset hypogonadism are markedly similar to those of Type 2 diabetes mellitus (T2DM) and metabolic syndrome, and ...
journal_title：Journal of diabetes
pub_type： 杂志文章,评审
doi：10.1111/j.1753-0407.2010.00085.x
更新日期：2010-09-01 00:00:00
abstract：BACKGROUND:To investigate the effect of hydroxypropyl methylcellulose (HPMC) on weight loss and metabolic disorders associated with obesity using a high-fat diet-induced obese mouse model under a high-fat diet regimen. METHODS: Obese male C57BL/6J (B6) mice were fed either a high-fat (60% kcal), low-fat (10% kcal), or...
journal_title：Journal of diabetes
pub_type： 杂志文章
doi：10.1111/j.1753-0407.2011.00118.x
更新日期：2011-06-01 00:00:00
abstract：BACKGROUND:Women with previous gestational diabetes mellitus (pGDM) are at increased risk of developing type 2 diabetes later in life. The aim of this study was to determine if circulating levels of metabolic hormones 12 weeks following a GDM pregnancy are associated with an increased risk of type 2 diabetes 8-10 years...
journal_title：Journal of diabetes
pub_type： 杂志文章
doi：10.1111/1753-0407.12209
更新日期：2015-07-01 00:00:00
abstract：:Diabetes mellitus is a metabolic disease with a considerable impact on healthcare owing to its increased prevalence and high mortality rate. Structural, morphological, and physiological changes in each of the ocular components have been described in detail. Autofluorescence has been described as a good indicator of me...
journal_title：Journal of diabetes
pub_type： 杂志文章,评审
doi：10.1111/1753-0407.12423
更新日期：2016-09-01 00:00:00
abstract：BACKGROUND: Diabetic peripheral neuropathy (DPN) is one of the complications of type 2 diabetes mellitus (T2DM) that decreases the quality of life of T2DM patients. Very few studies have found an association between the development and progression of DPN in T2DM and angiotensin-converting enzyme (ACE) gene insertion/d...
journal_title：Journal of diabetes
pub_type： 杂志文章
doi：10.1111/j.1753-0407.2012.00205.x
更新日期：2012-09-01 00:00:00
abstract：BACKGROUND:Adipocyte fatty acid-binding protein (A-FABP) has been recognized as an important player in macrophage cholesterol trafficking and inflammation, and may promote the development of atherosclerosis. To further elucidate the role of A-FABP in atherosclerosis in diabetes, we investigated the relationship between...
journal_title：Journal of diabetes
pub_type： 杂志文章
doi：10.1111/1753-0407.12549
更新日期：2018-06-01 00:00:00
abstract：BACKGROUND:In addition to its glucoregulatory actions, exendin-4, a stable glucagon-like peptide-1 receptor agonist, exhibits protective effects in the pancreas and anti-obesity effects. Suitable combination treatment with other anti-obesity or pancreas protective agents would be an effective approach to optimize these...
journal_title：Journal of diabetes
pub_type： 杂志文章
doi：10.1111/j.1753-0407.2012.00227.x
更新日期：2013-06-01 00:00:00
abstract：BACKGROUND:The aim of the present study was to determine the prevalence and risk factors of prediabetes and diagnosed and undiagnosed diabetes mellitus (DM) in rural Bangladesh. METHODS:Using a population-based cluster random sampling strategy, 3104 adults aged ≥30 years were recruited. Fasting capillary blood glucose...
journal_title：Journal of diabetes
pub_type： 杂志文章
doi：10.1111/1753-0407.12294
更新日期：2016-03-01 00:00:00
abstract：BACKGROUND:The present study investigated the correlation between urinary α1 -microglobulin as a marker of tubular dysfunction and albumin excretion in children and adolescents with type 1 diabetes (T1D). METHODS:Ninety-two Egyptian patients with T1D were included in the study (mean [± SD] age 14.14 ± 5.13 years). The...
journal_title：Journal of diabetes
pub_type： 杂志文章
doi：10.1111/1753-0407.12383
更新日期：2017-01-01 00:00:00
abstract：:Following on from impressive economic development and urbanization, China is currently experiencing a high prevalence of metabolic syndrome. Patients with metabolic syndrome suffer from the "The Deadly Quartet" of hyperglycemia, hypertriglyceridemia, hypertension, and central (or upper body) obesity. Current treatment...
journal_title：Journal of diabetes
pub_type： 杂志文章,评审
doi：10.1111/j.1753-0407.2010.00090.x
更新日期：2010-12-01 00:00:00
abstract：BACKGROUND:Convincing evidence indicates that the consumption of inulin-type fructans, inulin, and oligofructose has beneficial effects on blood glucose changes in animal models, although data in humans have been considered equivocal. As such, a systematic review of available literature on humans was conducted to evalu...
journal_title：Journal of diabetes
pub_type： 杂志文章,meta分析,评审
doi：10.1111/j.1753-0407.2010.00099.x
更新日期：2011-03-01 00:00:00
abstract：BACKGROUND:The aim of the present study was to assess the quality of diabetes care and characteristics of the healthcare system in underdeveloped rural mountain areas of western China. METHODS:Questionnaires were used to collect data from 288 diabetic patients with a multistage cluster sampling method in Zhongjiang Co...
journal_title：Journal of diabetes
pub_type： 杂志文章
doi：10.1111/1753-0407.12433
更新日期：2017-05-01 00:00:00
abstract：BACKGROUND:Liver X receptors (LXRs) including LXRα and LXRβ are members of the nuclear hormone receptor superfamily of ligand activated transcription factors, which serve as lipid sensors to regulate expression of genes controlling many aspects of cholesterol and fatty acid metabolism. The liver is the central organ in...
journal_title：Journal of diabetes
pub_type： 杂志文章
doi：10.1111/1753-0407.12081
更新日期：2014-05-01 00:00:00
abstract：BACKGROUND:Glucagon-like peptide-1 (GLP-1) and its stable analogue exendin-4 maintain glucose homeostasis by modulating insulin secretion from pancreatic β-cells and controlling hepatic glucose output. Glucokinase (GK), by catalysing the first step in glycolysis, plays an important role in glucose-stimulated insulin se...
journal_title：Journal of diabetes
pub_type： 杂志文章
doi：10.1111/j.1753-0407.2012.00193.x
更新日期：2012-12-01 00:00:00
abstract：BACKGROUND:The aim of the present study was to develop a simple nomogram that can be used to predict the risk of diabetes mellitus (DM) in the asymptomatic non-diabetic subjects based on non-laboratory- and laboratory-based risk algorithms. METHODS:Anthropometric data, plasma fasting glucose, full lipid profile, exerc...
journal_title：Journal of diabetes
pub_type： 杂志文章
doi：10.1111/1753-0407.12310
更新日期：2016-05-01 00:00:00
abstract：BACKGROUND:Glucose excursions and hypoglycemia are associated with cardiovascular complications. However, no studies have evaluated glucose excursions and the frequency of hypoglycemia in patients treated with mitiglinide/voglibose versus glimepiride as add-on to dipeptidyl peptidase-4 inhibitor therapy. METHODS:This ...
journal_title：Journal of diabetes
pub_type： 杂志文章,随机对照试验
doi：10.1111/1753-0407.12658
更新日期：2018-08-01 00:00:00
abstract：BACKGROUND:Elevated blood or urinary concentrations of endocrine-disrupting chemicals (EDCs) may be related to increased risk of type 2 diabetes (T2D). The aim of the present study was to assess the role of EDCs in affecting risk of T2D and related metabolic traits. METHODS:MEDLINE was searched for cross-sectional and...
journal_title：Journal of diabetes
pub_type： 杂志文章,meta分析,评审
doi：10.1111/1753-0407.12325
更新日期：2016-07-01 00:00:00
abstract：:Pancreatic β-cells secrete insulin when blood glucose levels become high; however, when β-cells are chronically exposed to hyperglycemia, β-cell function gradually deteriorates, which is known as β-cell glucose toxicity. In the diabetic state, nuclear expression of the pancreatic transcription factors pancreatic and d...
journal_title：Journal of diabetes
pub_type： 杂志文章,评审
doi：10.1111/1753-0407.12331
更新日期：2016-03-01 00:00:00
abstract：BACKGROUND:Intrahepatic expression of dipeptidyl peptidase-4 (DPP4), and circulating DPP4 (cDPP4) levels and its enzymatic activity, are increased in non-alcoholic fatty liver disease (NAFLD) and in type 2 diabetes mellitus and/or obesity. DPP4 has been implicated as a causative factor in NAFLD progression but few stud...
journal_title：Journal of diabetes
pub_type： 杂志文章
doi：10.1111/1753-0407.12237
更新日期：2015-11-01 00:00:00
abstract：BACKGROUND:Uncontrolled diabetes mellitus causes neuronal damage because of increased intracellular glucose. Natural products as complementary therapy may reduce neuronal complications. This study investigated whether fish oil (FO) and wheat germ oil (WGO) supplementation protects the brain in streptozotocin (STZ)-indu...
journal_title：Journal of diabetes
pub_type： 杂志文章
doi：10.1111/1753-0407.12518
更新日期：2017-11-01 00:00:00
abstract：BACKGROUND:Primary care physicians frequently encounter people with type 2 diabetes mellitus (T2DM) with discordant values for fasting glucose and HbA1c. The aim of this study was to identify the prevalence and characteristics of people in whom blood glucose and HbA1c did not match. METHODS:Overall, 64 553 people with...
journal_title：Journal of diabetes
pub_type： 杂志文章
doi：10.1111/1753-0407.12823
更新日期：2018-12-01 00:00:00
abstract：BACKGROUND:There is little information on medication use, trends across time, and the impact of guidelines on appropriate use of antidiabetic drugs in participants with type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD). METHODS:A cross-sectional analysis of the National Health and Nutrition Examination...
journal_title：Journal of diabetes
pub_type： 杂志文章
doi：10.1111/1753-0407.13003
更新日期：2020-05-01 00:00:00
abstract：BACKGROUND:It is clear that aerobic training (AT) can delay pancreatic exhaustion and slow the progression from prediabetes to type 2 diabetes (T2D), but there is little information regarding the effects of resistance training (RT) in people with prediabetes. This study compared the effectiveness of RT and AT in improv...
journal_title：Journal of diabetes
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1111/1753-0407.12955
更新日期：2020-01-01 00:00:00
abstract：BACKGROUND:Considerable uncertainty remains about obstructive lung function( OLF) in adults with metabolic syndrome (MetS). The aim of the present study was to examine pulmonary function status in adults with and without MetS. METHODS:We used data from 3109 participants aged ≥20 years of the National Health and Nutrit...
journal_title：Journal of diabetes
pub_type： 杂志文章
doi：10.1111/1753-0407.12136
更新日期：2014-11-01 00:00:00
abstract：BACKGROUND:Few studies have focused on postprandial incretin responses to different carbohydrate meals. Therefore, we designed a study to compare the different effects of two carbohydrates (75 g oral glucose, a monosaccharide and 100 g standard noodle, a polysaccharide, with 75 g carbohydrates equivalently) on postpran...
journal_title：Journal of diabetes
pub_type： 杂志文章,随机对照试验
doi：10.1111/1753-0407.12245
更新日期：2015-11-01 00:00:00
abstract：BACKGROUND:Cross-sectional studies have reported a close association between serum lipopolysaccharide-binding protein (LBP) and many metabolic disorders. However, no longitudinal study has explored the relationship between LBP and type 2 diabetes mellitus (T2DM). The aim of the present study was to investigate the asso...
journal_title：Journal of diabetes
pub_type： 杂志文章
doi：10.1111/1753-0407.12281
更新日期：2016-03-01 00:00:00
abstract：BACKGROUND:An increase in the prevalence of type 2 diabetes mellitus occurs in immigrants from developing regions to Western countries. However, the dynamics of these transitions in relation to the duration of residence in the new environment are not clearly defined. METHODS:Data concerning cardiovascular risk factors...
journal_title：Journal of diabetes
pub_type： 杂志文章
doi：10.1111/1753-0407.12215
更新日期：2015-07-01 00:00:00
abstract：:Skin autofluorescence is increased in diabetes, rises with age, and predicts diabetes-related complications. Exposure to secondhand smoke, because one or more family members are smokers, further increases skin autofluorescence in children and young adults with type 1 diabetes. Elimination of passive smoking should be ...
journal_title：Journal of diabetes
pub_type： 信件
doi：10.1111/1753-0407.12498
更新日期：2017-03-01 00:00:00
abstract：BACKGROUND:This meta-analysis was performed to quantitatively evaluate the dose-response association between obstructive sleep apnea (OSA) and risk of type 2 diabetes mellitus (T2DM). METHODS:PubMed, Embase, and Web of Science were searched up to 12 December 2018 for articles that assessed the OSA-T2DM association. Ra...
journal_title：Journal of diabetes
pub_type： 杂志文章
doi：10.1111/1753-0407.13017
更新日期：2020-06-01 00:00:00
abstract：BACKGROUND:A1c, a surrogate measure of glycemic control, is known to have a strong linear correlation with mean plasma glucose (MPG) when analyzed in populations of patients. However, clinically significant intersubject variability in this relationship exists, which suggests that A1c measurements may not reflect actual...
journal_title：Journal of diabetes
pub_type： 杂志文章
doi：10.1111/j.1753-0407.2010.00066.x
更新日期：2010-06-01 00:00:00
