Significance of different imidazoline receptors in pancreas and CNS and their role in control of plasma glucose, plasma insulin, lipid profile and blood pressure in fructose induced insulin resistant rats

ABSTRACT

The present study was carried out to elucidate the main difference between the various types of imidazoline receptors in the CNS and pancreas. The second generation selective imidazoline receptor agonist rilmenidine was used as a tool in the present study to demonstrate the difference of action on imidazoline receptors in these sites. An animal model of fructose induced insulin resistance in rats, similar to the metabolic syndrome X in human was adopted in the present work. The present study proved the ability of imidazoline receptor agonist rilmenidine to block ATP sensitive K+ channels, involved in the release of insulin in the pancreas via stimulation of 13 receptors. It also proved the ability of rilmenidine to normalize metabolic changes on lipid profile and to correct dyslipidemia that occurred in this condition. Moreover, rilmenidine lowered raised systolic blood pressure in fructose induced insulin resistant rats; due to additional effect on imidazoline I1 receptors in kidney, besides the main action on RVLM [rostral ventrolateral medulla] the final common pathway for sympathetic vasomotor outflow. The results revealed highly significant reduction of plasma glucose by 40.02%*, plasma insulin by 25.45%* and lipid profile [cholesterol by 25.42%*, triglycerides by 24.86%* and LDL by 44.92%*], while HDL was increased by 57.92%* [p<0.001] in insulin resistant group treated with rilmenidine. It also produced significant drop in the systolic blood pressure [p<0.001]. The difference in this action amounted to 30.91%* drop in BP with rilmenidine, compared with non-treated fructose induced insulin resistant group and insignificant change from normal control group [p>0.05]. In conclusion, the present work proved the presence of imidazoline binding site I3 in pancreas, previously called non I1 or I2. It also proved the effect of imidazoline receptor agonist rilmenidine to normalize the metabolic and haemodynamic effects that occur in fructose induced insulin resistant rats, supporting its use in diabetic hypertensive patients and in the metabolic syndrome X