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The Possible Mechanisms of the Impaired Insulin Secretion in Hypothyroid Rats.

Godini A, Ghasemi A, Zahediasl S - PLoS ONE (2015)

Bottom Line: Glucokinase and hexokinase specific activity, glucokinase content, and glucose transporter 2 protein expression were also determined in the isolated islets.In the presence of glucose concentrations of 8.3 mmol/L and 16.7 mmol/L, nifedipine was able to diminish insulin secretion from isolated islets of both groups, indicating that probably the defect may not arise from L type calcium channels or the steps beyond depolarization or the elements involved in the acetylcoline signaling pathway.In conclusion, the results of this study indicated that hypothyroidism reduced insulin secretion from isolated pancreatic islets, which confirms the finding of the previous studies; in addition, the insulin secretion deficit observed in hypothyroid rats may arise from the abnormalities in some parts of the glucose sensor apparatus of the pancreatic islets including glucokinase activity and glucose transporter 2 protein expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Neurophysiology Research Center, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

ABSTRACT
Although the insulin secretion deficit in hypothyroid male rats has been documented, the underling mechanisms of the effect of hypothyroidism on insulin secretion are not clear. Isolated islets of the PTU-induced hypothyroid and control rats were exposed to glibenclamide, acetylcholine, and nifedipine in the presence of glucose concentrations of 2.8 or 8.3 and 16.7 mmol/L. Glucokinase and hexokinase specific activity, glucokinase content, and glucose transporter 2 protein expression were also determined in the isolated islets. Isolated islets from the hypothyroid rats showed a defect in insulin secretion in response to high glucose. In the presence of glibenclamide or acetylcholine, the isolated islets from the hypothyroid and control rats stimulated by glucose concentration of 16.7 mmol/L secreted similar amounts of insulin. In the presence of glucose concentrations of 8.3 mmol/L and 16.7 mmol/L, nifedipine was able to diminish insulin secretion from isolated islets of both groups, indicating that probably the defect may not arise from L type calcium channels or the steps beyond depolarization or the elements involved in the acetylcoline signaling pathway. Glucokinase content and hexokinase specific activity were also the same in the control and hypothyroid groups. On the other hand, glucokinase specific activity and glucose transporter 2 protein expression were significantly (p<0.001 and p<0.01 respectively) lower in the islets isolated from the hypothyroid rats (6.50 ± 0.46 mU/min/mg protein and 0.55 ± 0.09 arbitrary unit) compared to the controls (10.93 ± 0.83 mU/min/mg protein and 0.98 ± 0.07 arbitrary unit) respectively. In conclusion, the results of this study indicated that hypothyroidism reduced insulin secretion from isolated pancreatic islets, which confirms the finding of the previous studies; in addition, the insulin secretion deficit observed in hypothyroid rats may arise from the abnormalities in some parts of the glucose sensor apparatus of the pancreatic islets including glucokinase activity and glucose transporter 2 protein expression.

No MeSH data available.


Related in: MedlinePlus

Insulin secretion by islets exposed to glucose concentration 8.3 and 16.7 mmol/L in the presence of nifedipine 5 μmol/L.Each bar presents the mean±SEM from 12–17 batches of eight islets from 5 or 6 rats, incubated for 60 min in 1 ml of medium containing the glucose concentrations and nifedipine. Differences were analyzed by Mann Whitney test. *p<0.05, **p<0.01 represent statistically significant differences, the PTU induced hypothyroid rats versus the controls. ×p<0.05, ×××p<0.001 represent statistically significant differences, in the presence of nifedipine compared to its absence in each group.
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pone.0131198.g004: Insulin secretion by islets exposed to glucose concentration 8.3 and 16.7 mmol/L in the presence of nifedipine 5 μmol/L.Each bar presents the mean±SEM from 12–17 batches of eight islets from 5 or 6 rats, incubated for 60 min in 1 ml of medium containing the glucose concentrations and nifedipine. Differences were analyzed by Mann Whitney test. *p<0.05, **p<0.01 represent statistically significant differences, the PTU induced hypothyroid rats versus the controls. ×p<0.05, ×××p<0.001 represent statistically significant differences, in the presence of nifedipine compared to its absence in each group.

Mentions: Results showed that nifedipine could diminish insulin secretion significantly in response to glucose concentrations of 8.3 and 16.7 mmol/L in both groups (Fig 4).


The Possible Mechanisms of the Impaired Insulin Secretion in Hypothyroid Rats.

Godini A, Ghasemi A, Zahediasl S - PLoS ONE (2015)

Insulin secretion by islets exposed to glucose concentration 8.3 and 16.7 mmol/L in the presence of nifedipine 5 μmol/L.Each bar presents the mean±SEM from 12–17 batches of eight islets from 5 or 6 rats, incubated for 60 min in 1 ml of medium containing the glucose concentrations and nifedipine. Differences were analyzed by Mann Whitney test. *p<0.05, **p<0.01 represent statistically significant differences, the PTU induced hypothyroid rats versus the controls. ×p<0.05, ×××p<0.001 represent statistically significant differences, in the presence of nifedipine compared to its absence in each group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488449&req=5

pone.0131198.g004: Insulin secretion by islets exposed to glucose concentration 8.3 and 16.7 mmol/L in the presence of nifedipine 5 μmol/L.Each bar presents the mean±SEM from 12–17 batches of eight islets from 5 or 6 rats, incubated for 60 min in 1 ml of medium containing the glucose concentrations and nifedipine. Differences were analyzed by Mann Whitney test. *p<0.05, **p<0.01 represent statistically significant differences, the PTU induced hypothyroid rats versus the controls. ×p<0.05, ×××p<0.001 represent statistically significant differences, in the presence of nifedipine compared to its absence in each group.
Mentions: Results showed that nifedipine could diminish insulin secretion significantly in response to glucose concentrations of 8.3 and 16.7 mmol/L in both groups (Fig 4).

Bottom Line: Glucokinase and hexokinase specific activity, glucokinase content, and glucose transporter 2 protein expression were also determined in the isolated islets.In the presence of glucose concentrations of 8.3 mmol/L and 16.7 mmol/L, nifedipine was able to diminish insulin secretion from isolated islets of both groups, indicating that probably the defect may not arise from L type calcium channels or the steps beyond depolarization or the elements involved in the acetylcoline signaling pathway.In conclusion, the results of this study indicated that hypothyroidism reduced insulin secretion from isolated pancreatic islets, which confirms the finding of the previous studies; in addition, the insulin secretion deficit observed in hypothyroid rats may arise from the abnormalities in some parts of the glucose sensor apparatus of the pancreatic islets including glucokinase activity and glucose transporter 2 protein expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Neurophysiology Research Center, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

ABSTRACT
Although the insulin secretion deficit in hypothyroid male rats has been documented, the underling mechanisms of the effect of hypothyroidism on insulin secretion are not clear. Isolated islets of the PTU-induced hypothyroid and control rats were exposed to glibenclamide, acetylcholine, and nifedipine in the presence of glucose concentrations of 2.8 or 8.3 and 16.7 mmol/L. Glucokinase and hexokinase specific activity, glucokinase content, and glucose transporter 2 protein expression were also determined in the isolated islets. Isolated islets from the hypothyroid rats showed a defect in insulin secretion in response to high glucose. In the presence of glibenclamide or acetylcholine, the isolated islets from the hypothyroid and control rats stimulated by glucose concentration of 16.7 mmol/L secreted similar amounts of insulin. In the presence of glucose concentrations of 8.3 mmol/L and 16.7 mmol/L, nifedipine was able to diminish insulin secretion from isolated islets of both groups, indicating that probably the defect may not arise from L type calcium channels or the steps beyond depolarization or the elements involved in the acetylcoline signaling pathway. Glucokinase content and hexokinase specific activity were also the same in the control and hypothyroid groups. On the other hand, glucokinase specific activity and glucose transporter 2 protein expression were significantly (p<0.001 and p<0.01 respectively) lower in the islets isolated from the hypothyroid rats (6.50 ± 0.46 mU/min/mg protein and 0.55 ± 0.09 arbitrary unit) compared to the controls (10.93 ± 0.83 mU/min/mg protein and 0.98 ± 0.07 arbitrary unit) respectively. In conclusion, the results of this study indicated that hypothyroidism reduced insulin secretion from isolated pancreatic islets, which confirms the finding of the previous studies; in addition, the insulin secretion deficit observed in hypothyroid rats may arise from the abnormalities in some parts of the glucose sensor apparatus of the pancreatic islets including glucokinase activity and glucose transporter 2 protein expression.

No MeSH data available.


Related in: MedlinePlus