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.
Highlights
Thyroid hormones are the critical regulators of metabolism in many cells; derangement of thyroid function can affect many organs
Results of this study confirm that hypothyroidism reduces glucose stimulated insulin secretion in rats, a finding that may be due to abnormality in some parts of glucose sensor apparatus of the beta cells, including glucose transporter 2 (GLUT2) protein levels and glucokinase specific activity
Our results show that observed decreased insulin secretion may not be related to L type calcium channels, the steps beyond depolarization, the elements involved in the acetylcholine-signaling pathway, or changes in hexokinase activity or glucokinase content
Summary
Thyroid hormones are the critical regulators of metabolism in many cells; derangement of thyroid function can affect many organs. It is believed that thyroid hormone is a physiological stimulus for the postnatal maturation of functional beta cells [1, 2]. Effects of hypothyroidism on insulin secretion have not been clearly elucidated. Lack of experiments on the human isolated islets insulin secretion in hypothyroidism is apparent but literature review reveals that all studies on animal isolated islets report impaired and not increased insulin secretion in response to glucose in hypothyroidism. Enhanced insulin response or concentrations that have been reported in some homeostatic models or glucose tolerance tests in hypothyroid humans or animals could attribute to insulin resistance, changes in insulin clearance, sex differences, or extent of thyroid hormones reduction, needs to be clarified. The underlying mechanisms of the effect of hypothyroidism on insulin secretion are not yet clear
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