Abstract:
:Newer classes of medications have been proven useful in glycemic control in type 2 diabetes (T2D), but many do not appear capable to slow down the progressive loss of ß-cell function, or to improve population-level glycemic control. Positive energy balance, e.g. surplus energy intake over expenditure, is at the core for developing metabolic syndrome and T2D. Currently available glycemic control drugs come to the market based on their 1-2 years risk-benefit profiles, but most of them do not correct positive energy balance and lose efficacy in the long-term. This denouement is destined by a positive energy balance of T2D. There is continuous endeavor/investment in new drugs for T2D. In this review, we compared the effects of commonly used oral hypoglycemic agents on energy balance and discussed several novel therapeutic targets/approaches for T2D that could potentially correct positive energy balance: changing the composition of intestinal host-microbiota to alleviate excess caloric consumption, controlling chylomicron uptake into intestinal lacteals to reduce excessive caloric intake, and activating pyruvate kinase M2 (PKM2) to ameliorate glucose metabolism and increase energy expenditure. We further reviewed how nicotine affects body weight and ameliorates positive energy balance, and ways to encourage people to adopt a more healthy lifestyle by exercising more and/or decreasing caloric intake. These potential targets/approaches may hopefully correct positive energy balance, delay disease progression, reverse some pathophysiological changes, and eventually prevent and/or cure the disease. Drug development strategies applying new insights into T2D process and therapeutic index to correct positive energy balance need to be seriously considered.
journal_name
Curr Drug Targetsjournal_title
Current drug targetsauthors
Liu Z,Yang Bdoi
10.2174/1389450120666181217111500subject
Has Abstractpub_date
2019-01-01 00:00:00pages
879-890issue
8eissn
1389-4501issn
1873-5592pii
CDT-EPUB-95256journal_volume
20pub_type
杂志文章,评审abstract::Thrombus formation at a site of arterial injury (eg, rupture of an atherosclerotic plaque in a carotid artery), a crucial step in the pathogenesis of cerebral ischemia, is initiated by the adhesion of platelets to the arterial wall. In vivo, activated platelets release adenosine diphosphate (ADP), whose binding to the...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945010790711987
更新日期:2010-03-01 00:00:00
abstract::Novel anti-vasculature strategies that are emerging for the treatment of cancer and for the inhibition of angiogenesis may be a promising new tool for the adjuvant therapy of malignant tumours. Over the last fifteen years, several reports have been published concerning the relationship between tumour progression and a...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945009789577954
更新日期:2009-10-01 00:00:00
abstract::An understanding of the historical paths that have lead to our current state of knowledge in the field of platelet studies can be both illuminating and inspiring. Considering that the existence and function of platelets were initially described just barely over 100 years ago it is exciting to recognize how far our kno...
journal_title:Current drug targets
pub_type: 历史文章,杂志文章
doi:10.2174/138945011797635858
更新日期:2011-11-01 00:00:00
abstract::Histone deacetylases are a class of enzymes that play important roles in post translational modifications of histones by deacetylating the lysine residues as well as interacting with various non-histone proteins. This type of enzymes is closely related to oncogenesis and has been proved to be attractive targets for de...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450115666140306152642
更新日期:2014-06-01 00:00:00
abstract::Oxysterols are pleiotropic messengers interacting with multiple receptor systems. One of the cognate receptors for oxysterols is EBI2, a G protein-coupled receptor highly expressed in the cells of the immune system. Here we discuss the receptor's role in the adapted immunity and inflammation as well as the receptor's ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666160217123042
更新日期:2016-01-01 00:00:00
abstract::Epigenetic modifications ensure the maintenance of normal cellular functions, and their dysregulation is frequently found in many disease states, including cancer. Nowadays, the most studied epigenetic dysregulation associated with tumorigenesis, cancer progression and metastasis refers to the variations in DNA methyl...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450121666200325093104
更新日期:2020-01-01 00:00:00
abstract::The adenosine pathway is a powerful evolutionarily selected mechanism aimed at a fine modulation of inflammatory responses and protection of tissues from injuries. Adenosine exerts its modulatory effects via interaction with G protein-coupled receptors, designated as A(1), A(2A), A(2B) and A(3). In this regard, extrac...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945012800564095
更新日期:2012-06-01 00:00:00
abstract::Immunity is a balanced status with adequate biological defenses to recognize and fight "non-self", as well as adequate tolerance to recognize "self". To maintain this immune homeostasis, a well-organized T cell immune network is required, which in part depends on the well-controlled development of alternative effector...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666161124145641
更新日期:2017-01-01 00:00:00
abstract::Trauma-induced coagulopathy (TIC) is a recently described condition which traditionally has been diagnosed by the common coagulation tests (CCTs) such as prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (aPTT), platelet count, and fibrinogen levels. The varying sensitivit...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450117666160310153211
更新日期:2016-01-01 00:00:00
abstract::Crohn's disease (CD) and ulcerative colitis (UC), two chronic and relapsing inflammatory bowel diseases (IBD), are supposed to develop in genetically-predisposed individuals as a result of an excessive immune mucosal response directed against normal components of the gut microbiota. There is also evidence that defects...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/13894501113149990157
更新日期:2013-11-01 00:00:00
abstract:BACKGROUND:Lymphatic filariasis is a pervasive and life-threatening disease for human beings. Currently, 893 million people in 49 countries worldwide affected by lymphatic filariasis as per WHO statistics. The concealed aspects of lymphatic diseases such as delayed disease detection, inappropriate disease imaging, the ...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450121666200630111250
更新日期:2020-01-01 00:00:00
abstract::The contribution of proteases to developmental, physiological and pathological processes has been well accepted. Cleavage of matrix proteins is a key requirement for cell migration and remodeling of the extracellular environment. The constant process of matrix turnover is dependent on the delicate balance between degr...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945008785909365
更新日期:2008-10-01 00:00:00
abstract::Transport molecules can significantly affect the pharmacodynamics and pharmacokinetics of drugs. An important transport molecule, the 170 kDa P-glycoprotein (Pgp), is constitutively expressed at several organ sites in the human body. Pgp is expressed at the blood-brain barrier, in the kidneys, liver, intestines and in...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945006778019264
更新日期:2006-08-01 00:00:00
abstract::The development of databases devoted to biological information opened the possibility to integrate, query and analyze biological data obtained from several sources that otherwise would be scattered through the web. Several issues arise in the handling of biological information, mainly due to the diversity of biologica...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945009787581195
更新日期:2009-03-01 00:00:00
abstract::Recently, the presence of functional interaction between the opioid and cannabinoid system has been shown in various pharmacological responses. Although there is an increasing interest for the feasible therapeutic application of a co-administration of cannabinoids and opioids in some disorders (i.e. to manage pain, to...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945010790980367
更新日期:2010-04-01 00:00:00
abstract::Epidemiological studies indicate that anti-inflammatory drugs, especially the non-steroidal anti-inflammatory drugs (NSAIDs), decrease the risk of developing Alzheimer's disease (AD). Their beneficial effects may be due to interference in the chronic inflammatory reaction, that takes place in AD. The best-characterize...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450033490902
更新日期:2003-08-01 00:00:00
abstract::The recent marketing of two selective cyclooxygenase-2 (COX-2) inhibitors, celecoxib and rofecoxib is remarkable considering that COX-2 was only discovered eight years ago as a growth factor- and cytokine-inducible gene. Concomitant with these pharmaceutical successes is the advances in our understanding of the molecu...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450013348830
更新日期:2001-03-01 00:00:00
abstract::Enzymes are proteins that act as biological catalysts to speed up cellular biochemical processes. According to their main Enzyme Commission (EC) numbers, enzymes are divided into six categories: EC-1: oxidoreductase; EC-2: transferase; EC-3: hydrolase; EC-4: lyase; EC-5: isomerase and EC-6: synthetase. Different enzym...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450119666181002143355
更新日期:2019-01-01 00:00:00
abstract::PDZ domains play an essential role in a number of cellular processes by facilitating protein scaffolding and assembly of protein complexes. These domains consist of 80 to 90 amino acids and are found to recognize short C-terminal sequences of target proteins. Protein complex formation between PDZ target molecules can ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450116666141219120125
更新日期:2015-01-01 00:00:00
abstract::Using a portable infusion pump, intravenous opioid patient-controlled analgesia (PCA) permits a patient to self-deliver a small bolus of opioid to achieve prompt relief without over sedation. Use of PCA for pain management is increasing in hospitals, largely because it can provide equivalent or better analgesia than c...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945005774574524
更新日期:2005-11-01 00:00:00
abstract::Multifunctional rational drug design of protein tyrosine kinases inhibitors allows a potent drug to be utilized to treat more than one disease for greater patient benefits. Many protein tyrosine kinases (PTK), including Janus kinase 3 (JAK3) and Bruton's tyrosine kinase (BTK), have been identified as potential drug ta...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945006776054997
更新日期:2006-03-01 00:00:00
abstract::The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play an important role in the generation of pacemaker activity of cardiac sinoatrial node cells and immature cardiomyocytes. HCN channels are also present in adult atrial and ventricular cardiomyocytes, where the physiological role is currently und...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450116666150531152047
更新日期:2015-01-01 00:00:00
abstract::Recent developments in computer power and chemoinformatics methodology make possible that a huge amount of data become available through internet. These databases are devoted to a wide spectrum of scientific fields. Here we are concerned with databases related to protein-drug interactions. More specifically, databases...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945008786949379
更新日期:2008-12-01 00:00:00
abstract::Neutrophil-dominated inflammation plays an important role in many airway diseases including asthma, chronic obstructive pulmonary disease (COPD), bronchiolitis and cystic fibrosis. In cases of asthma where neutrophil-dominated inflammation is a major contributing factor to the disease, treatment with corticosteroids c...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945011794751555
更新日期:2011-04-01 00:00:00
abstract:OBJECTIVE:To investigated the use of mixed treatment comparison (MTC) meta-analysis models to summarize results from randomized clinical trials (RCTs) on approved pharmacological treatments for neovascular age-related macular degeneration (AMD). METHODS:The number of patients with visual loss or visual gain of 3 or mo...
journal_title:Current drug targets
pub_type: 杂志文章,meta分析,评审
doi:10.2174/138945011794182665
更新日期:2011-02-01 00:00:00
abstract::The Wnt signaling pathway has important functions in development, tissue homeostasis, and regeneration. Deregulation of canonical Wnt/beta-catenin signaling is frequently found in various human cancers, particularly in colorectal cancer, and non-canonical Wnt signaling pathways also have been implicated in neoplasia. ...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/138945008784911769
更新日期:2008-07-01 00:00:00
abstract::Efficient drug delivery systems are exceedingly important for novel drug discovery. The evidence-based personalized medicine (EBPM) promises to deliver the right drug at the right time to a right patient as it covers clinicallysignificant genetic predisposition and chronopharmacological aspects of nanotheranostics. Re...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:
更新日期:2014-01-01 00:00:00
abstract::Tuberculosis (TB) is an infectious disease caused by the pathogen Mycobacterium tuberculosis (M. tuberculosis), killing about two million people worldwide each year. An increase in the prevalence of drug-resistant strains of M. tuberculosis in the past decades has renewed focus on the development of new drugs that can...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450111314060009
更新日期:2013-06-01 00:00:00
abstract::The pivotal role of 5-HT in the control of appetite was formally proposed nearly 30 years ago. In particular endogenous hypothalamic 5-HT has been implicated in the processes of within meal satiation and the end state of post meal satiety. Of the numerous 5-HT receptor subtypes currently identified, 5-HT(1B) and 5-HT(...
journal_title:Current drug targets
pub_type: 杂志文章,评审
doi:10.2174/1389450053174550
更新日期:2005-03-01 00:00:00
abstract::Seventy five percent of hospitalized patients with Crohn's disease suffer from malnutrition. One third of Crohn's disease patients have a body mass index below 20. Sixty percent of Crohn's disease patients have sarcopenia. However some inflammatory bowel disease (IBD) patients are obese or suffer from sarcopenic-obesi...
journal_title:Current drug targets
pub_type: 杂志文章
doi:10.2174/1389450115666140930150047
更新日期:2014-01-01 00:00:00