Effect of streptozotocin-induced diabetes on rat brain sulfonylurea binding sites.
Both high and low affinity sulfonylurea receptors (SURs) reside on glucose responsive neurons where they influence cell firing and neurotransmitter release via the adenosinetriphosphate (ATP)-sensitive K+ (katp) channel. Here, the effect of diabetes on [3H] glyburide binding to SURs was assessed in male obesity-resistant Sprague-Dawley rats rendered diabetic with streptozotocin (65 mg/kg, i.p.). Additional streptozotocin-treated rats were supplemented with insulin (1.5 U/kg/ day). Streptozotocin reduced plasma insulin to 13% of control associated with hyperglycemia (25.3 +/- 1.7 mmol/l), while insulin lowered plasma glucose (9.56 +/- 1.78 mmol/l) to near control levels (7.65 +/- 0.22 mmol/l). Over 7 days, all streptozotocin-treated rats lost 12% of their initial body wt. while controls gained 1%. Despite equivalent wt. loss, streptozotocin-induced diabetes selectively increased high affinity [3H] glyburide binding in the hypothalamic dorsomedial nuclei (DMN) and ventromedial nuclei (VMN) and lateral area (LH). This was prevented by insulin injections. Low affinity binding was similarly increased in the DMN and VMN, as well as two amygdalar subnuclei but decreased in the substantia nigra, pars compacta. Insulin fully prevented these changes only in the DMN and one amygdalar nucleus and the substantia nigra. Therefore, binding to (SURs) appears to be generally upregulated in the face of hypoinsulinemia with hyperglycemia and this is prevented by insulin treatment. These and other data suggest that this combination of abnormalities in diabetes should have an adverse effect on the glucose sensing capacity of the brain.
Levin
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BE
Neurology Service (127C), VA Medical Center, East Orange, NJ 07018-1095, USA. levin@umdnj.edu
Dunn-Meynell
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AA
D000679:Amygdala / Q000737:chemistry / Q000502:physiology; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007031:Hypothalamus / Q000737:chemistry / Q000502:physiology; D049528:Insulin, Long-Acting / Q000097:blood / Q000494:pharmacology; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000737:chemistry / Q000502:physiology; D013453:Sulfonylurea Compounds / Q000378:metabolism*; D014316:Tritium
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D013453:Sulfonylurea Compounds; D014316:Tritium; D005905:Glyburide