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In rat pancreatic islets, β-cell gene expression, survival, and subsequent acute glucose stimulation of insulin secretion (GSIS) are optimally preserved by prolonged culture at 10 mM glucose (G10) and markedly altered by culture at G5 or G30. Here, we tested whether pharmacological glucokinase (GK) activation prevents these alterations during culture or improves GSIS after culture. Rat pancreatic islets were cultured 1-7 days at G5, G10, or G30 with or without 3 μM of the GK activator Ro 28-0450 (Ro). After culture, β-cell apoptosis and islet gene mRNA levels were measured, and the acute glucose-induced increase in NAD(P)H autofluorescence, intracellular calcium concentration, and insulin secretion were tested in the absence or presence of Ro. Prolonged culture of rat islets at G5 or G30 instead of G10 triggered β-cell apoptosis and reduced their glucose responsiveness. Addition of Ro during culture differently affected β-cell survival and glucose responsiveness depending on the glucose concentration during culture: it was beneficial to β-cell survival and function at G5, detrimental at G10, and ineffective at G30. In contrast, acute GK activation with Ro increased the glucose sensitivity of islets cultured at G10 but failed at restoring β-cell glucose responsiveness after culture at G5 or G30. We conclude that pharmacological GK activation prevents the alteration of β-cell survival and function by long-term culture at G5 but mimics glucotoxicity when added to G10. The complex effects of glucose on the β-cell phenotype result from changes in glucose metabolism and not from an effect of glucose per se.
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http://dx.doi.org/10.1152/ajpendo.00154.2015 | DOI Listing |
Biomed Khim
December 2024
Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria; College of Health Sciences, Osun State University, Osogbo, Osun State, Nigeria.
Cerebral malaria (CM) is a fatal complication of Plasmodium falciparum infection. The biological and physiological links between CM, inflammation, and inflammasome, point to the complexity of its pathology. Resistance to available and affordable drugs, worsening economic crisis, and urgent need for integration of orthodox with traditional/alternative medicine, actualized the search for sustainable pharmacotherapy.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Physiology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
Diabetes can affect male fertility via oxidative stress and endocrine system disruption. Nanomedicine based on natural products is employed to address diabetes complications. The current study aims to investigate the potential beneficial effect of propolis extract nanoparticles against diabetes-induced testicular damage in male rats.
View Article and Find Full Text PDF3 Biotech
January 2025
Plant Cell Biotechnology (PCBT) Department, Central Food Technological Research Institute (CFTRI), Mysuru, 570 020 India.
Unlabelled: The present study evaluated the effects of 5-methyltetrahydrofolate (5-MTHF) and aqueous extract on diabetes. An in silico docking study with select bioactive compounds showed strong binding affinities of folates with glucose metabolism-related proteins. In vitro assay showed 5-MTHF's superior inhibitory activity on alpha-amylase compared to folic acid.
View Article and Find Full Text PDFGenes Genomics
December 2024
Department of Endocrinology, Shenzhen Traditional Chinese Medicine Hospital, No. 1, Futian District, Shenzhen, 518033, Guangdong, China.
Background: Baihu Jia Renshen Decoction (BJRD) is used for diabetes mellitus (DM) management in clinics.
Objective: To elucidate the potential mechanism of BJRD in treating type 1 DM (T1DM).
Methods: T1DM models were established via intraperitoneal injection of streptozotocin (STZ).
J Nutr Biochem
December 2024
Molecular Biology Unit, Department of Biochemistry, School of Life Sciences, Federal University of Technology, Akure, Nigeria. Electronic address:
The combustion of diesel in engines contributes polycyclic aromatic hydrocarbons to Diesel Particulate Matter (DPM) present in the atmosphere, therefore causing toxic mitigating consequences by eliciting oxidative modulation. Currently, type 2 diabetes mellitus is reported as a global menace, causing about 1.5 million deaths in 2019 and contributing to about 48% of related deaths among the populace aged below 70 years.
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