scholarly journals Different insulin-secretory responses to calcium-channel blockers in islets of lean and obese (ob/ob) mice

1988 ◽  
Vol 249 (2) ◽  
pp. 401-407 ◽  
Author(s):  
M A Black ◽  
L A Fournier ◽  
H M Heick ◽  
N Bégin-Heick

The purpose of these experiments was to determine whether the activity of the voltage-dependent Ca2+ channel was modulated in the same manner in islets of the ob/ob mouse as in islets of homozygous lean mice of the same strain. The effect of agents that are known to alter the concentrations and movements of intracellular Ca2+ were investigated in relation to glucose-stimulated insulin secretion and in relation to the effect of forskolin. In islets of obese mice, verapamil and nifedipine both inhibited glucose-induced insulin release, nifedipine being the more potent inhibitor. Forskolin-stimulated secretion was inhibited either not at all (verapamil) or much less (nifedipine) in islets of the ob/ob mouse compared with those of lean mice. At basal glucose concentrations, verapamil initiated insulin secretion in islets of the ob/ob mouse and acted synergistically with forskolin to evoke a secretory activity that was 3-fold greater than that evoked by 20 mM-glucose. Nifedipine also initiated secretion at basal glucose concentrations and acted synergistically with forskolin, but its effect was considerably smaller than that of verapamil. A comparison of the effect of forskolin in the presence of Ca2+-channel blockers and in the absence of Ca2+ suggests that, in the obese mouse, the operation of the voltage-dependent Ca2+ channel is impaired.

2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Tingting Yang ◽  
Lin-Ling He ◽  
Ming Chen ◽  
Kun Fang ◽  
Henry M. Colecraft

2009 ◽  
Vol 60 (2) ◽  
pp. 157-164 ◽  
Author(s):  
Nazila Pourkhalili ◽  
Shirin Pournourmohammadi ◽  
Fatemeh Rahimi ◽  
Sanaz Vosough-Ghanbari ◽  
Maryam Baeeri ◽  
...  

Comparative Effects of Calcium Channel Blockers, Autonomic Nervous System Blockers, and Free Radical Scavengers On Diazinon-Induced Hyposecretion Of Insulin From Isolated Islets of Langerhans in RatsHyperglycaemia has been observed with exposure to organophosphate insecticides. This study was designed to compare the effects of calcium channel blockers, alpha-adrenergic, beta-adrenergic, and muscarinic receptor blockers, and of free radical scavengers on insulin secretion from diazinon-treated islets of Langerhans isolated from the pancreas of rats using standard collagenase digestion, separation by centrifugation, and hand-picking technique. The islets were then cultured in an incubator at 37 °C and 5 % CO2. In each experimental set 1 mL of 8 mmol L-1 glucose plus 125 μg mL-1 or 625 μg mL-1 of diazinon were added, except for the control group, which received 8 mmol L-1 glucose alone. The cultures were then treated with one of the following: 30 μmol L-1 atropine, 100 μmol L-1 ACh + 10 μmol L-1 neostigmine, 0.1 μmol L-1 propranolol, 2 μmol L-1 nifedipine, 50 μmol L-1 phenoxybenzamine, or 10 μmol L-1 alphatocopherol. In all experiments, diazinon significantly reduced glucose-stimulated insulin secretion at both doses, showing no dose dependency, as the average inhibition for the lower dose was 62.20 % and for the higher dose 64.38 %. Acetylcholine and alpha-tocopherol restored, whereas atropine potentiated diazinon-induced hyposecretion of insulin. Alpha-, beta- and calcium channel blockers did not change diazinon-induced effects. These findings suggest that diazinon affects insulin secretion mainly by disturbing the balance between free radicals and antioxidants in the islets of Langerhans and by inducing toxic stress.


1986 ◽  
Vol 238 (3) ◽  
pp. 863-869 ◽  
Author(s):  
M Black ◽  
H M Heick ◽  
N Bégin-Heick

To determine whether the abnormal insulin-secretory activity encountered in obese mice is due to an anomaly in the production of cyclic AMP, islets of lean and obese mice were incubated with forskolin under various conditions. Our data show that, in addition to the well-known quantitative differences in insulin-secretory activity between islets of lean and obese mice, there are important qualitative differences. The islets of obese mice accumulated less cyclic AMP than did those of lean mice in response to given doses of forskolin, yet their insulin secretion was enhanced to much higher values. In the islets of obese mice, but not in those of lean mice, the stimulatory effect of forskolin on insulin secretion was evident even at non-stimulatory concentrations of glucose or in Ca2+-deprived incubation media, showing that the islet of the obese mouse is less dependent on a primary stimulus (glucose) and on the provision of normal concentrations of Ca2+ in the bathing medium than is the islet of the lean mouse.


2013 ◽  
Vol 104 (2) ◽  
pp. 358a
Author(s):  
Tingting Yang ◽  
Lin-Ling He ◽  
Ming Chen ◽  
Kun Fang ◽  
Henry M. Colecraft

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