The reversal effect of insulin on diabetes-induced alterations in beta adrenergic and muscarinic receptors in rat prostate.
Previous studies from our laboratory demonstrated that 8 weeks after the induction of diabetes by the administration of streptozotocin (STZ) there was a downregulation of beta adrenergic and muscarinic cholinergic receptors in rat prostate, and that early insulin treatment (started 3 days after the onset of diabetes) prevented these alterations from occurring. In the present study, the effects of later insulin treatment (started 8 weeks after the onset of diabetes) on the reversibility of diabetes-induced alterations in beta adrenergic and muscarinic receptors in rat prostate were investigated. Three groups of rats were maintained for 16 weeks: 1) diabetics, 2) insulin-treated diabetics (subcutaneously injected with 5 to 8 U per day starting 8 weeks after the onset of diabetes) and 3) age matched controls. Binding studies with [3H]dihydroalprenolol (DHA) and [3H]quinuclidinyl benzilate (QNB) showed a significantly lower density of beta adrenergic and muscarinic cholinergic receptors in the diabetic rat prostate than in prostate from either controls or insulin-treated diabetic animals. Inhibition of [3H]DHA binding by isoproterenol, a beta adrenergic agonist, and binding of [3H]QNB by carbachol, a muscarinic agonist, indicated the presence of low and high affinity agonist binding sites for each receptor. The relative proportion of high affinity to total binding sites as well as the low and high affinity constants were similar in all groups. These data indicate that insulin treatment, begun 8 weeks after the onset of diabetes, can reverse the diabetes-induced downregulation of both beta adrenergic and muscarinic cholinergic receptors in STZ-diabetic rat prostates.
Section of Urology, Yale University School of Medicine, New Haven, Connecticut 06510.
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Y
Fukumoto
M
M
Yoshida
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S
Dokita
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T
Kamai
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RM
Weiss
J
J
Latifpour
D000818:Animals; D001665:Binding Sites; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D011467:Prostate / Q000737:chemistry / Q000294:innervation*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D007328:Insulin; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic