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Cumulative data showing the relative frequencies of LCR events during the peak of the responses to hyperosmotic sucrose, hyperosmotic CaCl 2 , or after transient exposure to a hypoosmotic solution in the absence or presence of <t>nifedipine.</t> ***, statistically significant differences (P
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1) Product Images from "DHPR activation underlies SR Ca2+ release induced by osmotic stress in isolated rat skeletal muscle fibers"

Article Title: DHPR activation underlies SR Ca2+ release induced by osmotic stress in isolated rat skeletal muscle fibers

Journal: The Journal of General Physiology

doi: 10.1085/jgp.200910191

Cumulative data showing the relative frequencies of LCR events during the peak of the responses to hyperosmotic sucrose, hyperosmotic CaCl 2 , or after transient exposure to a hypoosmotic solution in the absence or presence of nifedipine. ***, statistically significant differences (P
Figure Legend Snippet: Cumulative data showing the relative frequencies of LCR events during the peak of the responses to hyperosmotic sucrose, hyperosmotic CaCl 2 , or after transient exposure to a hypoosmotic solution in the absence or presence of nifedipine. ***, statistically significant differences (P

Techniques Used:

Representative confocal x-y images (1/second) obtained from fluo-4–loaded FDB fibers before, during, and after exposure to solutions of increased or decreased osmolarity. For each cell, the number of LCR events observed per frame throughout the experiment is indicated in the graph on the right. (A) The application of a hyperosmotic sucrose solution was often associated with a marked elevation of [Ca 2+ ], and LCR was difficult to identify (cell 1). However, where the rise in [Ca 2+ ] was less pronounced, individual LCR events were apparent during the application of sucrose (cell 2). Prior exposure to 100 µM nifedipine, to inhibit the DHPR, prevented LCR upon sucrose exposure (cell 3). (B) The introduction of a hyperosmotic CaCl 2 solution induced LCR (cell 1), which was markedly inhibited in the presence of nifedipine (cell 2). (C) The application of a hypoosmotic (254 mOsm) solution had no apparent effect on [Ca 2+ ] i . However, returning to the isoosmotic solution precipitated LCR events (cell 1). In the presence of nifedipine, transient exposure to a hypoosmotic solution failed to induce LCR (cell 2). Fibers subject to hypoosmotic Tyrode's exposure were initially exposed to isoosmotic Tyrode for 30 s, and then for 2 min to a hypoosmotic before returning to isoosmotic Tyrode's solution for 4 min. Horizontal bar, 20 µm.
Figure Legend Snippet: Representative confocal x-y images (1/second) obtained from fluo-4–loaded FDB fibers before, during, and after exposure to solutions of increased or decreased osmolarity. For each cell, the number of LCR events observed per frame throughout the experiment is indicated in the graph on the right. (A) The application of a hyperosmotic sucrose solution was often associated with a marked elevation of [Ca 2+ ], and LCR was difficult to identify (cell 1). However, where the rise in [Ca 2+ ] was less pronounced, individual LCR events were apparent during the application of sucrose (cell 2). Prior exposure to 100 µM nifedipine, to inhibit the DHPR, prevented LCR upon sucrose exposure (cell 3). (B) The introduction of a hyperosmotic CaCl 2 solution induced LCR (cell 1), which was markedly inhibited in the presence of nifedipine (cell 2). (C) The application of a hypoosmotic (254 mOsm) solution had no apparent effect on [Ca 2+ ] i . However, returning to the isoosmotic solution precipitated LCR events (cell 1). In the presence of nifedipine, transient exposure to a hypoosmotic solution failed to induce LCR (cell 2). Fibers subject to hypoosmotic Tyrode's exposure were initially exposed to isoosmotic Tyrode for 30 s, and then for 2 min to a hypoosmotic before returning to isoosmotic Tyrode's solution for 4 min. Horizontal bar, 20 µm.

Techniques Used:

(A) Simultaneous records of E m (top) and the fura-2 fluorescence ratio (bottom) from fibers equilibrated with an isoosmotic solution before transient exposure to solutions made hyperosmotic (404 mOsm) by the addition of sucrose, mannitol, or CaCl 2 , or hypoosmotic (254 mOsm) by decreasing [NaCl] (left-right). (B) The effects of hyperosmotic sucrose or CaCl 2 solutions on E m (top) and the fura-2 fluorescence ratio (bottom) in cells exposed to 100 µM nifedipine to inhibit DHPR activation. (C) Substitution of 100 mM Na + for K + resulted in a sustained depolarization. Thereafter, the introduction of hyperosmotic sucrose solution had no apparent effect on [Ca 2+ ] i , whereas the application of 30 mM caffeine induced a robust [Ca 2+ ] i transient. (D) Accumulated data showing both the relative change in fluorescence ratio (filled bars) and E m (open bars) obtained using the protocols shown in A and B. Bars represent the mean (± SEM), and the number of preparations is indicated in parentheses. **, mean values significantly different to the peak values obtained after the introduction of hyperosmotic sucrose (P
Figure Legend Snippet: (A) Simultaneous records of E m (top) and the fura-2 fluorescence ratio (bottom) from fibers equilibrated with an isoosmotic solution before transient exposure to solutions made hyperosmotic (404 mOsm) by the addition of sucrose, mannitol, or CaCl 2 , or hypoosmotic (254 mOsm) by decreasing [NaCl] (left-right). (B) The effects of hyperosmotic sucrose or CaCl 2 solutions on E m (top) and the fura-2 fluorescence ratio (bottom) in cells exposed to 100 µM nifedipine to inhibit DHPR activation. (C) Substitution of 100 mM Na + for K + resulted in a sustained depolarization. Thereafter, the introduction of hyperosmotic sucrose solution had no apparent effect on [Ca 2+ ] i , whereas the application of 30 mM caffeine induced a robust [Ca 2+ ] i transient. (D) Accumulated data showing both the relative change in fluorescence ratio (filled bars) and E m (open bars) obtained using the protocols shown in A and B. Bars represent the mean (± SEM), and the number of preparations is indicated in parentheses. **, mean values significantly different to the peak values obtained after the introduction of hyperosmotic sucrose (P

Techniques Used: Fluorescence, Activation Assay

2) Product Images from "Radiomanganese PET Detects Changes in Functional β-Cell Mass in Mouse Models of Diabetes"

Article Title: Radiomanganese PET Detects Changes in Functional β-Cell Mass in Mouse Models of Diabetes

Journal: Diabetes

doi: 10.2337/db16-1285

In vivo assessment of functional β-cell mass by 52 Mn 2+ -PET. A : Coronal PET images at 1 h postinjection showing the pancreas of ICR mice given i.p. injections of diazoxide (20 mg/kg), nifedipine (20 mg/kg), or glibenclamide (5 mg/kg) before the administration of a 52 Mn 2+ rapid bolus. The pancreas (P) is demarcated by white dashed contours. B : Manual ROI-based quantification of 52 Mn 2+ uptake in various tissues from static PET images acquired at 1 h postinjection. C : Ex vivo biodistribution analysis after PET imaging at 1 h postinjection. Significantly reduced pancreatic uptake of 52 Mn 2+ is observed in mice that received nifedipine and diazoxide before radiotracer administration. Mice that received glibenclamide (5 mg/kg) before radiotracer administration had significantly higher pancreatic uptake of 52 Mn 2+ than the control mice, based on both PET imaging ( P = 0.02) and biodistribution ( P = 0.047) studies. Data are presented as mean ± SD ( n = 3–4 mice per group). *** P
Figure Legend Snippet: In vivo assessment of functional β-cell mass by 52 Mn 2+ -PET. A : Coronal PET images at 1 h postinjection showing the pancreas of ICR mice given i.p. injections of diazoxide (20 mg/kg), nifedipine (20 mg/kg), or glibenclamide (5 mg/kg) before the administration of a 52 Mn 2+ rapid bolus. The pancreas (P) is demarcated by white dashed contours. B : Manual ROI-based quantification of 52 Mn 2+ uptake in various tissues from static PET images acquired at 1 h postinjection. C : Ex vivo biodistribution analysis after PET imaging at 1 h postinjection. Significantly reduced pancreatic uptake of 52 Mn 2+ is observed in mice that received nifedipine and diazoxide before radiotracer administration. Mice that received glibenclamide (5 mg/kg) before radiotracer administration had significantly higher pancreatic uptake of 52 Mn 2+ than the control mice, based on both PET imaging ( P = 0.02) and biodistribution ( P = 0.047) studies. Data are presented as mean ± SD ( n = 3–4 mice per group). *** P

Techniques Used: In Vivo, Functional Assay, Positron Emission Tomography, Mouse Assay, Ex Vivo, Imaging

3) Product Images from "Fasiglifam (TAK‐875) has dual potentiating mechanisms via Gαq‐GPR40/FFAR1 signaling branches on glucose‐dependent insulin secretion. Fasiglifam (TAK‐875) has dual potentiating mechanisms via Gαq‐GPR40/FFAR1 signaling branches on glucose‐dependent insulin secretion"

Article Title: Fasiglifam (TAK‐875) has dual potentiating mechanisms via Gαq‐GPR40/FFAR1 signaling branches on glucose‐dependent insulin secretion. Fasiglifam (TAK‐875) has dual potentiating mechanisms via Gαq‐GPR40/FFAR1 signaling branches on glucose‐dependent insulin secretion

Journal: Pharmacology Research & Perspectives

doi: 10.1002/prp2.237

Synergistic effects on insulin secretion elicited by the induction of Ca 2+ influx and activation of protein kinase C. (A) Effects of nifedipine on the glucose‐stimulated insulin secretion potentiating effect of fasiglifam. Data are normalized to the vehicle (0 mmol/L glucose) group and shown as means ± SEM ( n = 3). *** P
Figure Legend Snippet: Synergistic effects on insulin secretion elicited by the induction of Ca 2+ influx and activation of protein kinase C. (A) Effects of nifedipine on the glucose‐stimulated insulin secretion potentiating effect of fasiglifam. Data are normalized to the vehicle (0 mmol/L glucose) group and shown as means ± SEM ( n = 3). *** P

Techniques Used: Activation Assay

Related Articles

Injection:

Article Title: Radiomanganese PET Detects Changes in Functional β-Cell Mass in Mouse Models of Diabetes
Article Snippet: .. VDCC blockade was achieved via i.p. injection of 20 mg/kg nifedipine (MP Biomedicals) dissolved in DMSO. .. To activate KATP channels, mice received an i.p. injection of 20 mg/kg diazoxide (Tocris Biosciences) in PBS, a clinically used KATP agonist, 15 min before injection of 0.74 MBq (20 μCi) of 52 Mn2+ .

other:

Article Title: DHPR activation underlies SR Ca2+ release induced by osmotic stress in isolated rat skeletal muscle fibers
Article Snippet: Stocks of 1 mM fura-2 AM (Biotium Inc.), 1 mM fluo-4 AM (Invitrogen), 1 mM tetracaine, 100 µM nifedipine (MP Biomedicals), 100 µM 9-AC (Alfa Aesar), 200 µM furosemide, or 1 mM bumetanide were dissolved in DMSO.

Incubation:

Article Title: Development of a Cell-Based Fluorescence Polarization Biosensor Using Preproinsulin to Identify Compounds That Alter Insulin Granule Dynamics
Article Snippet: .. The cells were then incubated for 1 h at 37°C in 2 mL of DMEM containing low glucose (5.6 mM), high glucose (25 mM) alone, and high glucose (25 mM) in the presence of 10 nM Exendin-4 (Cat. No. 1933; TOCRIS Bioscience) or 10 μM nifedipine (Cat. No 151743; MP Biomedicals, LLC). .. Following incubation, supernatants were collected to determine secreted insulin contents.