Details

Autor(en) / Beteiligte

• AREFANIAN, HOSSEIN
• BAHMAN, FATEMAH
• AL MADHOUN, ASHRAF
• ALZAID, FAWAZ
• SINDHU, SARDAR T.
• WILLIAMS, MICHAYLA R.
• ALRASHED, FATEMA
• NIZAM, RASHEEBA
• JACOB, SINDHU
• JOHN, SUMI E.
• ALHUSAYAN, MOHAMMED
• KURIAN, SHIBU J.
• ABUKHALAF, NERMEEN A.
• SHENOUDA, STEVE
• ALSAEED, HALEMAH
• KOCHUMON, SHIHAB P.
• ABU-FARHA, MOHAMED
• ABUBAKER, JEHAD
• THANGAVEL, ALPHONSE T.
• AHMAD, RASHEED
• ALMULLA, FAHD

Titel

1762-P: Increased Glucose Sensing and Insulin Secretion Induced by Verapamil Is Associated with Enhanced Oxygen Consumption Rate in MIN6 ß-Cells

Ist Teil von

• Diabetes (New York, N.Y.), 2023-06, Vol.72 (Supplement_1), p.1

Ort / Verlag

New York: American Diabetes Association

Erscheinungsjahr

2023

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• It has been shown recently that oral administration of verapamil in persons with type 1 diabetes (T1D) decreased the dependency on exogenous insulin and improved the β cell function. Additionally, it decreased the frequency of hypoglycemic events. This finding encouraged us to test the effect of verapamil on the function of MIN6 mouse β cell-line. Glucose-Stimulated Insulin Secretion (GSIS) assay was performed using static incubation method. MIN6 cells were pre-treated with 50 μM verapamil for 24 hours, then the levels of total insulin content and secreted insulin were measured before and after GSIS assay using highly sensitive mouse insulin ELISA kit. Glucose sensing was estimated by the percentage of secreted insulin over total insulin content for each concentration of glucose. The measured insulin levels were normalized by the level of total protein. Oxygen consumption rate (OCR) was measured using Seahorse system and metabolic stress kit. MIN6 cells were seeded in Agilent Seahorse XF96 cell culture microplate at a cell density of 4×104 cells/well, under normal (5.6 mM) and high (25.2 mM) glucose concentrations for 24 hours, after which, cells were treated with verapamil (50 μM) or left untreated and incubated for 24 hours. Our results show no significant difference between total insulin content of treated vs. untreated cells. GSIS data show that insulin secretion was significantly higher in verapamil-treated cells at 8.4, 11.2, and 16.8 mM, but not at 2.8 and 5.6 mM glucose. The results suggest that β cells were hypersensitized to glucose when treated with verapamil. In metabolic flux analysis for mitochondrial respiration, treatment with verapamil increased basal and maximal respiration. Taken together, our study showed that verapamil increased the level of glucose sensing and oxidative respiration under conditions of high glucose, which may explain its effect on lowering the frequency of hypoglycemic events in clinical studies. Disclosure H.Arefanian: None. S.E.John: None. M.Alhusayan: None. S.J.Kurian: None. N.A.Abukhalaf: None. S.Shenouda: None. H.Alsaeed: None. S.P.Kochumon: None. M.Abu-farha: None. J.Abubaker: None. A.T.Thangavel: None. F.Bahman: None. R.Ahmad: None. F.Almulla: None. A.Al madhoun: None. F.Alzaid: None. S.T.Sindhu: None. M.R.Williams: None. F.Alrashed: None. R.Nizam: None. S.Jacob: None. Funding Kuwait Foundation for the Advancement of Sciences (RACB-2019-001)