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Diabetes Mellitus/Anti-DM Pharmacological Management
Published in Mihai V. Putz, New Frontiers in Nanochemistry, 2020
Bogdan Bumbăcilă, Corina Duda-Seiman, Daniel Duda-Seiman, Mihai V. Putz
Dipeptidyl-peptidase IV is a complex enzyme that exists as a cell membrane peptidase and as a second smaller soluble form present in the circulation. Both GIP and GLP-1 are endogenous physiological substrates for DPP-4 and chemical inhibition of DPP-4 activity, or genetic inactivation of DPP-4 in rodents, results in increased levels of intact bioactive GIP and GLP-1. Sustained DPP-4 inhibition lowers blood glucose via stimulation of insulin and inhibition of glucagon secretion and is associated with preservation of β-cell mass in preclinical studies. Although DPP-4 cleaves dozens of regulatory peptides and chemokines in vitro, studies demonstrate that GIP and GLP-1 receptor-dependent pathway represent the dominant mechanisms transducing the glucoregulatory actions of DPP-4 inhibitors in vivo. The available preclinical data suggest that highly selective DPP-4 inhibition (because DPP-4 is a member of a complex gene family which encode other structural related enzymes) represents an effective and safe strategy for the therapy of type 2 diabetes (Drucker, 2007).
Skin development and regeneration, and the control of fibrosis
Published in David M. Gardiner, Regenerative Engineering and Developmental Biology, 2017
Michael S. Hu, H. Peter Lorenz, Michael T. Longaker
Through the use of recent technology, a subpopulation of dermal fibroblasts, originating from Engrailed-1 (En1)-expressing progenitors, has been identified as responsible for the bulk of connective tissue deposition during embryonic development and cutaneous wound healing. CD26, also known as dipeptidyl peptidase-4 (DPP4), was found to enrich for this lineage of fibroblasts. Dipeptidyl peptidase-4 is a cell-surface serine exopeptidase that cleaves X-proline dipeptides from the N-terminus of polypeptides. Inhibition of the enzymatic activity of DPP4 with a small-molecule selective allosteric inhibitor of peptidase activity resulted in decreased scarring. Moreover, the subpopulation of fibroblasts labeled by expression of En1 was shown to be responsible for both acute and chronic progressive forms of fibrosis (Rinkevich et al. 2015). Identification and depletion of these cellular culprits of scarring and fibrosis are promising for regenerative efforts.
Rediscovering the discovered: the new paradigm in repurposing drugs
Published in Indian Chemical Engineer, 2020
Togapur Pavan Kumar, Srivari Chandrasekhar, Prathama S. Mainkar
Competition is another aspect that can have a considerable effect on returns and market share of the drug. A new drug launch can revolutionise the management of a disease rendering other drugs used for similar therapeutic regime unpopular. The Gliptin series is one such example. Gliptins are used in the management of type 2 diabetes mellitus. Drugs to treat type 2 diabetes exhibited reduced efficiency in glycaemic control, and adverse effects such as weight gain, gastrointestinal distress, hypoglycemia and so on. The Gliptins or dipeptidyl peptidase-4 (DPP-4) inhibitors revolutionised type 2 diabetes mellitus management. It changed the clinicians’ approach in managing the disease [12]. The identification of one gliptin led to appearance of many ‘me too’ gliptins in quick succession.
COVID-19;-The origin, genetics,and management of the infection of mothers and babies
Published in Egyptian Journal of Basic and Applied Sciences, 2020
Hassan Ih El-Sayyad, Yousef Ka Abdalhafid
Most CoVs need receptor binding and intracellular proteolytic cleavage, for fusion to the host cells [141]. These have facilitated the function of the spike glycoprotein which interact with the host cell protein dipeptidyl peptidase 4 (DPP4, CD26) and managing viral entry [142]. In addition, the aminopeptidase N (APN) serves as a receptor for various CoVs including CCoV, HCoV-229E, FeCoV, and TGEV [143]. Aminopeptidase N is present within exosomes from mast cells [144] and glial cells [145]. Proteases of CoVs are transmembrane-anchored and essential for infection and intracellular connected with the type II transmembrane serine protease (TTSP) family [146].
Closed-loop control in insulin pumps for type-1 diabetes mellitus: safety and efficacy
Published in Expert Review of Medical Devices, 2020
Glucagon-like peptide-1 (GLP1) is another potential adjunctive option in closed-loop systems. Much like pramlintide it increases satiety, delays gastric emptying, and suppresses glucagon release [86]. It is already being used in type 2 diabetes as it increases residual insulin secretion in this group. There are several potential oral adjunctive medications such as dipeptidyl peptidase-4 inhibitors and SGLT2 inhibitors that may be combined with closed-loop systems to improve glucose control [86], although these drugs increase the risk of DKA and must, therefore, be approached with caution in people with type 1 diabetes.