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Objectives: Both the serine/threonine protein kinase Akt and the voltage-gated L-type calcium channel act as important players in glucose-stimulated insulin secretion. Akt recruits the L-type calcium channel to and maintains them in the plasma membrane. This study aimed to characterize the role of L-type calcium channels in mediation of Akt signaling in glucose-stimulated insulin secretion.
Methods: Insulin secretion was evaluated in rat pancreatic islets and INS-1 pancreatic β cells by a standard insulin radioimmunoassay.
Results: Akt inhibition effectively abrogates not only glucose-stimulated but also potassium depolarization-stimulated insulin secretion from rat islets, the latter critically relying on the voltage-gated calcium channel-mediated Ca(2+) influx without involvement of glucose metabolism. Likewise, Akt inhibition also reduces both glucose-stimulated and potassium depolarization-stimulated insulin secretion from INS-1 cells. Importantly, pharmacological ablation of L-type calcium channels partially blocks Akt inhibition-induced reduction in glucose-stimulated insulin secretion but completely prevents that in potassium depolarization-evoked insulin release from INS-1 cells. Furthermore, Akt inhibition does not influence calcium ionophore A23187-induced insulin secretion from INS-1 cells, which occurred without involvement of L-type calcium channels.
Conclusions: Akt signals upstream of L-type calcium channels to optimize glucose-stimulated insulin secretion.
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http://dx.doi.org/10.1097/MPA.0b013e31822363a9 | DOI Listing |
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia, insulin resistance, and decreased insulin secretion. With its rising global prevalence, effective management strategies are critical to reducing morbidity and mortality. This systematic review compares the efficacy, safety, and long-term outcomes of four major pharmacological treatments for T2DM: sodium-glucose cotransporter-2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, and insulin.
View Article and Find Full Text PDFDiabetes mellitus is a chronic metabolic disorder that can cause elevated blood glucose levels due to impaired insulin secretion or resistance. Different parts of have been used widely in traditional medicine to treat many disorders. The present study aims to evaluate the antidiabetic ability of the corm, pseudostem, inflorescence, fruit, peel, and seed of via in vitro experiments by inhibiting α-amylase and α-glucosidase enzymes as well as in vivo models on diabetic alloxan-induced mice.
View Article and Find Full Text PDFFront Endocrinol (Lausanne)
December 2024
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Background: Although immune checkpoint inhibitors (ICIs) are effective cancer drugs, ICI-induced diabetes is a rare but a life-threatening adverse event for patients. The deleterious action of ICI on pancreatic beta-cell function is a concern. However, the influence of ICI on insulin synthesis and secretion in patients with cancer without diabetes remains unknown.
View Article and Find Full Text PDFInt J Pharm
December 2024
College of Biological Science and Engineering, Fuzhou University, Fuzhou, 350108, China. Electronic address:
The effect of digestion on nanocarriers will affect the release and pharmacological effects of bioactive compounds in delivery systems. The digestion of cellulose is limited to gut microbiota, which offers a new research strategy for targeted delivery of bioactive compounds. Herein, positively charged cellulose-like chitosan/polyvinylpyrrolidone nanofiber was prepared to improve the residence time, colon target and gut microbiota regulation activity of quercetin decorated selenium nanoparticles (QUE@SeNPs/CS/PVPNFs).
View Article and Find Full Text PDFIntern Med
December 2024
Department of Diabetes, Endocrinology, and Metabolism, National Center for Global Health and Medicine, Japan.
There are no clear strategies for non-insulin-dependent slowly progressive type 1 diabetes mellitus (SPIDDM). We herein report a 25-year-old man with SPIDDM in whom appropriate diet therapy and exercise improved the initial insulin secretion without medication. After 12 months, his body weight decreased by 5.
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