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Allopathic Medicines
Published in Varma H. Rambaran, Nalini K. Singh, Alternative Medicines for Diabetes Management, 2023
Varma H. Rambaran, Nalini K. Singh
Dipeptidyl-peptidase IV (DPP-4) inhibitors, such as sitagliptin (Januvia: Figure 2.11a) and vildagliptin (Galvus: Figure 2.11b), are a new class of incretin-based therapies. Also known as gliptins, they work by blocking the activity of DPP-4 enzymes, which are known to break down the insulin-secreting and glucagon-inhibiting incretins: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) (Meier 2012).Structural formulae of dipeptidyl-peptidase IV (DPP-4) inhibitors: (a) sitagliptin and (b) vildagliptin.
Soybean-Based Functional Foods Through Microbial Fermentation: Processing and Biological Activities
Published in Megh R. Goyal, Arijit Nath, Rasul Hafiz Ansar Suleria, Plant-Based Functional Foods and Phytochemicals, 2021
Arijit Nath, Titas Ghosh, Abinit Saha, Klára Pásztorné Huszár, Szilvia Bánvölgyi, Renáta Gerencsérné Berta, Ildikó Galambos, Edit Márki, Gyula Vatai, Andras Koris, Arpita Das
Several soybean-derived peptides have anti-diabetic activity in addition to their anti-obesity activity [48, 59, 75]. Soybean-derived peptides (such as: Leu-Pro-Tyr-Pro, Iso-Ala-Val-Pro-Gly-Glu-Val-ala, and Iso-Ala-Val-Pro-Thr-Gly-Val-Ala) help glucose metabolism by supporting glucose uptake in liver cells by activation of glucose transporters (GLUT 1 and GLUT 4) [5]. The peptide, Iso-Ala-Val-Pro-Thr-Gly-Val-Ala, inhibits activity of dipeptidyl peptidase IV that is responsible for hydrolysis of peptide hormone glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide [52]. Furthermore, soybean-derived peptides can suppress the activity of α-glucosidase that is located at brush border of the enterocytes of jejunum in small intestine. It is a key enzyme for producing monosaccharide and their absorption on the gut-wall.
Therapeutic Potential of Anthocyanin Against Diabetes
Published in Hafiz Ansar Rasul Suleria, Megh R. Goyal, Health Benefits of Secondary Phytocompounds from Plant and Marine Sources, 2021
Tawheed Amin, H. R. Naik, Bazila Naseer, Syed Zameer Hussain
Anthocyanin-rich black bean coat extracts may decrease the generation of reactive oxygen species (ROS) up to 80% due to its antioxidant activity [84]. This reduction in ROS may protect and improve the ability of β-cells of islets of Langerhans, thereby suggesting an indirect role of anthocyanins in mitigation of diabetes. Dipeptidyl peptidase 4, an essential enzyme, is metabolically related to insulin secretion [84]. Anthocyanin-rich extracts obtained from the coats of black beans have been reported to inhibit Dipeptidyl peptidase 4 [84], thereby suggesting the role of anthocyanins in the prevention and management of diabetes.
Dipeptidyl peptidase 4 (DPP-4) inhibitors and the risk of lung cancer: current evidence and future directions
Published in Expert Review of Clinical Pharmacology, 2023
Harmanjit Singh, Jatin Sharma, Pallavi Sikarwar, Ashish Kumar Kakkar
Dipeptidyl-peptidase 4 (DPP-4) enzyme is a serine protease located on the cell surface and expressed ubiquitously. Its actions include deactivation of glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), and DPP-4 inhibition, therefore, potentiates the effects of these incretin hormones, facilitating insulin release, and inhibiting glucagon secretion [3,4]. DPP-4 cleaves several other substrates as well, including substance P (SP) and bradykinin. In general, DPP-4 inhibitors are clinically indicated as second line and third line agents for the management of type 2 diabetes mellitus (T2DM) [5,6]. Most commonly used DPP-4 inhibitors include sitagliptin, saxagliptin, linagliptin, vildagliptin, and alogliptin. Advantage of DPP-4 inhibitors over other oral hypoglycemic agents includes minimal requirement for dose titration, minimal or no hypoglycemia and ease of usage at any time, regardless of meals [7]. They can be used in elderly patients and in patients with heart disease as the incidence of hypoglycemia is low compared to other oral hypoglycemic agents [4]. Most common adverse effects associated with use of DPP-4 inhibitors include respiratory tract infections, nasopharyngitis, and headache amongst others [8].
Cardiac fibrosis: emerging agents in preclinical and clinical development
Published in Expert Opinion on Investigational Drugs, 2021
Roberto Spoladore, Giulio Falasconi, Giorgio Fiore, Silvana Di Maio, Alberto Preda, Massimo Slavich, Alberto Margonato, Gabriele Fragasso
Type-2 diabetes mellitus (T2DM) is a common cause of myocardial fibrosis influencing morbidity and mortality [57]. Despite molecular basis remains poorly understood [58], newer antidiabetic drugs have been shown to modulate extracellular matrix deposition in the heart [59] and to improve left ventricle positive remodeling [60]. Preclinical studies on GLP-1 receptors agonists were conducted using Liraglutide, which proved to decrease myocardial fibrosis through the inhibition of CTGF [61] and the enzymes involved in the synthesis of collagen [62]. This may explain the possible protecting effect of Liraglutide on diabetes-related diastolic disfunction [63,64]. An ongoing clinical trial will clarify its antiremodelling properties in T2DM patients with diastolic dysfunction [65]. Dipeptidyl peptidase (DPP)-4 inhibitors were tested in preclinical studies, sharing similar effects of Liraglutide [66,67]. Vidagliptin was similar to enalapril and superior to metformin in countering adverse cardiac remodeling in rats with myocardial infarction [68]. Interestingly, DPP4 is a large expressed marker in immune-system which would explain part of the immunomodulatory and immunoinflammatory effect of DPP-4 inhibitors [69].
Prediction of saxagliptin stability using a new approach based on Partial Least Squares and Design of Experiments
Published in Pharmaceutical Development and Technology, 2020
Nika Jordan, Jure Zakrajšek, Simona Bohanec, Robert Roškar, Iztok Grabnar
The active pharmaceutical ingredient of the drug product studied in the present study is a dipeptidyl peptidase-4 (DPP-4) inhibitor saxagliptin. It is a labile, chemically unstable compound which is prone to an intra-molecular cyclization (Peters 2007). The rate of intramolecular cyclization is accelerated when formulation is exposed to humidity. The analytical development team specified two main degradation products that can potentially arise significantly during storage. The first main known degradation product, hereafter termed as DP-1 is therapeutically inactive and therefore, its formation is not desirable. The chemical structure of the second known degradation product, termed as DP-2, alludes to drug substance and formic acid reaction (Figure 1). Formic acid is a degradation product of various polymers used as excipients, such as PEG (Robnik et al. 2019). Formation of formic acid can occur, if excipients have been exposed to stressful environment, especially oxidation (Wu et al. 2011).