Structure-Function Elucidation of Flavonoids by Modern Technologies
Dilip Ghosh, Pulok K. Mukherjee in Natural Medicines, 2019
Dipeptidyl peptidase IV (DPP IV) is an enzyme that cleaves N-terminal dipeptides from incretin hormones like glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP; Juillerat-Jeanneret 2013). The incretin hormones help in insulin secretion and inhibit glucagon secretion, consequently lowering postprandial blood glucose. Preventing the degradation of incretin hormones by DPP IV enzyme has thus become an effective strategy for diabetes without causing hypoglycaemia or weight gain (Matheeussen et al. 2012; Juillerat-Jeanneret 2013; Arulmozhiraja et al. 2016). In vitro assessment for DPP IV inhibitory activity by various phytochemicals has been described earlier by Matheeussen et al. (2012). Various reports have established the DPP IV inhibition activity of certain phytochemicals like quercetin (Semaan et al. 2017) and anthocyanins (Fan et al. 2013).
Liver, Gallbladder, and Exocrine Pancreas
Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard in Toxicologic Pathology, 2018
Several incretin-based therapies have been approved in the past few years for treatment of type 2 diabetes. These agents are either glucagon-like peptide (GLP)-1 receptor agonists or inhibitors of dipeptidylpeptidase-4 (DPP-4), a nonspecific enzyme that degrades GLP-1. Use of these drugs has been accompanied by several reports implicating them in acute pancreatitis and other alterations in the pancreas in humans (Ayoub et al. 2010; Butler et al. 2013; Iyer et al. 2012; Singh et al. 2013). Others fail to confirm these findings or question the methods used in those studies (Bonner-Weir et al. 2014; Engel et al. 2010; Garg et al. 2010; Monami et al. 2014). A summary of a detailed review of nonclinical and clinical data by the European Medicines Agency and Food and Drug Administration stated that assertions regarding safety of incretin-based therapies were inconsistent with the current data (Egan et al. 2014).
Psoriasis and Diabetes: An Unholy Alliance
Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi in Psoriasis and Psoriatic Arthritis, 2017
Incretin molecules accentuate glucose-mediated insulin release from the pancreatic beta cells. They are small peptides released from the gastrointestinal tract, the most important of them being glucagon-like peptide 1 (GLP-1). GLP-1 analogues are approved agents for managing type 2 diabetes with the added benefits of causing significant weight loss in obese patients with diabetes. GLP-1 receptors (GLP-1Rs) are widely distributed in the human body. Apart from the gastrointestinal tract from where it is released and islets of pancreas, GLP-1R has been identified in the kidneys, brain, heart, and T and B lymphocytes in mice and humans [31–33]. Incretin molecules have a role in T-cell migration, maturation, and activation. In a small study in patients of type 2 diabetes with psoriasis, 6 weeks therapy of GLP-1 analogues was associated with improvement in skin lesions of psoriasis, accompanied by a decrease in iNKT cells in the psoriatic skin plaques and a simultaneous increase in circulating levels of iNKT cells [30]. In keeping with the above observation, the GLP-1R antagonist exendin 9 has been shown to block the modulation of iNKT cell cytokine production by GLP-1 [30,34]. In another study, the treatment of seven patients with type 2 diabetes and psoriasis with the GLP-1 agonist liraglutide resulted in improvement in the clinical severity of psoriasis, along with a decrease in dermal γδ T-cell number and IL-17 expression [35]. Exenatide, another GLP-1 agonist, has also been shown to be beneficial in the resolution of skin lesions of psoriasis [36].
Emerging drugs for the treatment of diabetic nephropathy
Published in Expert Opinion on Emerging Drugs, 2022
Yoon Kook Kim, Xinyuan Ning, Kashif M. Munir, Stephen N. Davis
The mechanisms for the potential renal benefits of incretin-based therapy are not yet clear. Some data suggest the presence of GLP-1 receptors in the kidneys may play a role [36]. Preclinical and human data suggest that GLP-1 receptors are present on glomerular, tubular, and vascular cells in the kidney. There is also an ongoing question of the relevance of albuminuria in the progression of diabetic kidney disease, and more studies should evaluate the renoprotective effects of GLP-1RAs in relation to the progression of albuminuria. While no dedicated kidney outcomes trial for GLP-1RAs are available so far, the FLOW trial, NCT003819153, is currently ongoing and aims to evaluate the effect of semaglutide in the progression of CKD in patients with T2DM already on ACE-I or ARB [37].
Evogliptin for the treatment option for type 2 diabetes: an update of the literature
Published in Expert Review of Clinical Pharmacology, 2022
Ping Zou, Mingxing Guo, Jingbo Hu
As reported by the International Diabetes Federation (IDF) data, approximately 463 million adults aged 20 to 79 worldwide have type 2 diabetes (T2D) as of 2019, and it is expected that 700 million will get sick by 2045 [1]. Findings from the 9th edition of the IDF Diabetes Atlas also show that 19.3% (approximately 135.6 million) of the elderly aged 65 to 99 have diabetes [2]. What is worse, traditional hypoglycemic drugs have gradually shown poor tolerance, poor compliance, and so on. Metformin-mediated anti-hypoglycemic activity cannot be maintained due to the progressive deterioration of β-cell functions [3]. Moreover, sulphonylureas treatment inevitably induces weight gains [4]. Therefore, new therapeutic strategies are needed to keep blood glucose under control and avoid hypoglycemia and other side effects. Previous studies have shown that incretin hormone (glucagon-like peptide-1, GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) play an important role in glucose homeostasis [5]. However, the plasma half-life of GLP-1 and GIP is very short, and GLP-1 is easily inactivated by dipeptidyl peptidase 4 (DPP-4) enzyme in the circulation. Therefore, the development of GLP-1 analogues (incretin hormone analogues) and DPP-4 inhibitors (incretin potentiators) to prevent rapid inactivation of GIP and GLP-1 is an effective strategy for the treatment of T2D.
Protective effect of saxagliptin against renal ischaemia reperfusion injury in rats
Published in Archives of Physiology and Biochemistry, 2022
Suat Tekin, Asiye Beytur, Murat Cakir, Aslı Taslıdere, Yavuz Erden, Cigdem Tekin, Suleyman Sandal
Renal IRI produces intracellular damage and subsequent inflammatory reactions. Sepsis, shock, hypotension and some renal operations may cause kidney ischaemia, which is the beginning of the injury process. DPP-4 inhibitors provide a clinical benefit by increasing levels of glucose-lowering incretin hormones such as GLP-1 in patients having T2D (Wang et al.2012). According to preclinical data, there are preventive effects of DPP-4 inhibitors on IRI of the lungs and heart (Sauve et al.2010, Jungraithmayr et al.2012). Since DPP-4 is highly expressed in the kidneys (Mentlein 1999), the use of DPP-4 inhibitors may be considered in the removal/reduction of renal IRI. Some studies have investigated the possible protective effects of DPP-4 inhibitors in renal IR with conflicting results (Chang et al.2015, Nuransoy et al.2015). In the present study, protective effects of a DPP-4 inhibitor, saxagliptin, on oxidative stress and tubular damage caused by renal IRI in rats were determined.
Related Knowledge Centers
- Alpha Cell
- Beta Cell
- Peptide
- Metabolism
- Insulin
- Hormone
- Pancreatic Islets
- Blood Sugar Level
- Glucagon
- Glucagon-Like Peptide-1