Prior to the discovery of insulins, diabetes was managed predominantly by dietary interventions. Discovery of insulin and its first human trial highlighted the need for higher purity insulin thereby steering the subsequent journey of insulin development. Considering the limitations of the early preparations like short duration of action and need for several injections per day, attempts at protracting the duration of insulin action were made. This led to the development of intermediate-acting Neutral Protamine Hagedorn (NPH) and the Lente family of insulins. This review provides insights into the discovery of insulins and the shortcomings of early protracted release preparations, which in turn, gave impetus to the search for a 'true' basal insulin, which could mimic the endogenous human basal insulin secretion.
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PNAS Nexus
January 2025
Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, 3501 Fifth Avenue, Pittsburgh, PA 15261, USA.
Bronchopulmonary dysplasia, the most prevalent chronic lung disease of prematurity, is often treated with glucocorticoids (GCs) such as dexamethasone (DEX), but their use is encumbered with several adverse somatic, metabolic, and neurologic effects. We previously reported that systemic delivery of the GC prodrug ciclesonide (CIC) in neonatal rats activated glucocorticoid receptor (GR) transcriptional responses in lung but did not trigger multiple adverse effects caused by DEX. To determine whether limited systemic metabolism of CIC was solely responsible for its enhanced safety profile, we treated neonatal rats with its active metabolite desisobutyryl-ciclesonide (Des-CIC).
View Article and Find Full Text PDFPharm Res
January 2025
Department of Urology, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA.
Metabolic alterations are commonly associated with various cancers and are recognized as contributing factors to cancer progression, invasion, and metastasis. Drug repurposing, a strategy in drug discovery, utilizes existing knowledge to recommend established drugs for new indications based on clinical data or biological evidence. This approach is considered a less risky alternative to traditional drug development.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Anesthesiology, Laboratory and Clinical Research Institute for Pain, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Metabolic dysfunction has been demonstrated to contribute to diabetic pain, pointing towards a potential correlation between glucose metabolism and pain. To investigate the relationship between altered glucose metabolism and neuropathic pain, we compared samples from healthy subjects with those from intervertebral disc degeneration (IVDD) patients, utilizing data from two public datasets. This led to the identification of 412 differentially expressed genes (DEG), of which 234 were upregulated and 178 were downregulated.
View Article and Find Full Text PDFEcotoxicol Environ Saf
January 2025
Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, China; Global Health Research Center, Dalian Medical University, No. 9 West Section Lvshun South Road, Dalian 116044, China. Electronic address:
Sodium arsenite (NaAsO), the most common form of inorganic arsenic prevalent in the environment, has been closely linked to islet β-cell dysfunction, a critical pathological hallmark of type 2 diabetes (T2D). Even though apoptosis plays a pivotal role in arsenic-induced islet β-cell dysfunction, the explicit underlying mechanisms remain elusive. Here, we have identified that the SET-Rac1 signaling pathway is instrumental in the apoptosis and dysfunction of islet β-cells induced by NaAsO.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
January 2025
Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United States.
Diabetic cardiomyopathy (DMCM), defined as left ventricular dysfunction in the setting of diabetes mellitus without hypertension, coronary artery disease or valvular heart disease, is a well-recognized entity whose prevalence is certainly predicted to increase alongside the rising incidence and prevalence of diabetes mellitus. The pathophysiology of DMCM stems from hyperglycemia and insulin resistance, resulting in oxidative stress, inflammation, cardiomyocyte death, and fibrosis. These perturbations lead to left ventricular hypertrophy with associated impaired relaxation early in the course of the disease, and eventually culminating in combined systolic and diastolic heart failure.
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