Activation of I2-imidazoline receptors by agmatine improved insulin sensitivity through two mechanisms in type-2 diabetic rats.
In an attempt to clarify the role of endogenous opioid in peripheral I2-imidazoline receptors activation for improvement of insulin action, bilateral adrenalectomy was carried out in rats with insulin resistance induced by 4-week fructose-rich chow feeding. Single intravenous (i.v.) injection of agmatine (1mg/kg) for 30 min increased the plasma beta-endorphin-like immunoreactivity (BER) in a way parallel to the reduction of plasma glucose in sham-operated fructose chow-fed rats; this action of agmatine was totally abolished by BU224 at sufficient dosage (1mg/kg, i.v.) to block I2-imidazoline receptors. The plasma glucose lowering effect of agmatine was markedly reduced but not totally deleted by adrenalectomy in fructose chow-fed rats. A direct effect of agmatine on glucose homeostasis can thus be considered. The hyperinsulinemic-euglycemic clamp technique was performed to evaluate insulin sensitivity. The effect of agmatine on elevation of the average rate of glucose infusion at the glucose clamp steady state in sham-operated fructose chow-fed rats was lessen in adrenalectomized fructose chow-fed rats, but was completely abolished by BU224. The obtained results suggest that the improvement of insulin sensitivity by agmatine is produced by two mechanisms, stimulation of adrenal gland to enhance beta-endorphin secretion and a direct activation of peripheral I2-imidazoline receptor in tissues, for the amelioration of insulin action.
Department of Otorhinolaryngology, Mackay Memorial Hospital, Taipei City 10401, Taiwan, ROC.
Chin-Hui
CH
Su
I-Min
IM
Liu
Hsien-Hui
HH
Chung
Juei-Tang
JT
Cheng
D000315:Adrenalectomy; D000376:Agmatine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004032:Diet; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005632:Fructose / Q000378:metabolism; D015309:Glucose Clamp Technique; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D054755:Imidazoline Receptors / Q000819:agonists / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D001615:beta-Endorphin / Q000097:blood
C105826:BU 224; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007093:Imidazoles; D054755:Imidazoline Receptors; D007328:Insulin; C487767:imidazoline receptor 2; D005632:Fructose; D001615:beta-Endorphin; D000376:Agmatine