title: Regulation of KATP channel subunit gene expression by hyperglycemia in the mediobasal hypothalamus of female rats.
abstract: The ATP-sensitive potassium (K(ATP)) channels are gated by intracellular adenine nucleotides coupling cell metabolism to membrane potential. Channels comprised of Kir6.2 and SUR1 subunits function in subpopulations of mediobasal hypothalamic (MBH) neurons as an essential component of a glucose-sensing mechanism in these cells, wherein uptake and metabolism of glucose leads to increase in intracellular ATP/ADP, closure of the channels, and increase in neuronal excitability. However, it is unknown whether glucose and/or insulin may also regulate the gene expression of the channel subunits in the brain. The present study investigated whether regulation of K(ATP) channel subunit gene expression might be a mechanism by which neuronal populations adapt to prolonged changes in glucose and/or insulin levels in the periphery. Ovariectomized, steroid-replaced rats were fitted with indwelling jugular catheters and infused for 48 h with saline, glucose (hyperglycemia-hyperinsulinemia), insulin and glucose (hyperinsulinemia), diazoxide (control), or glucose and diazoxide (hyperglycemia). At the end of infusions, the MBH, preoptic area, and pituitary were dissected for RNA isolation and RT-PCR. Hyperglycemia decreased Kir6.2 mRNA levels in the MBH in both the presence and absence of hyperinsulinemia. These same conditions also produced a trend toward decreased SUR1 mRNA levels in the MBH; however, it did not exceed statistical significance. Hyperglycemia increased whereas hyperinsulinemia reduced neuropeptide Y mRNA levels when these groups were compared with each other. However, neither was significantly different from values observed in saline-infused controls. In conclusion, hyperglycemia per se may alter expression of K(ATP) channels and thereby induce changes in the excitability of some MBH neurons.
authors.affiliation: Department of Neurobiology and Physiology, Northwestern University, 2205 Tech Dr., Evanston, IL 60208, USA.
authors.forename: Maricedes
authors.initials: M
authors.lastname: Acosta-Martínez
authors.forename: Jon E
authors.initials: JE
authors.lastname: Levine
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D003981:Diazoxide / Q000008:administration & dosage / Q000494:pharmacology; D004338:Drug Combinations; D004967:Estrogens / Q000097:blood / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D006943:Hyperglycemia / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D006946:Hyperinsulinism / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009478:Neuropeptide Y / Q000235:genetics; D009994:Osmolar Concentration; D010052:Ovariectomy; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011333:Pro-Opiomelanocortin / Q000235:genetics; D011374:Progesterone / Q000097:blood / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
chemical_list: D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D003981:Diazoxide; D004338:Drug Combinations; D004967:Estrogens; D005947:Glucose; D007328:Insulin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009478:Neuropeptide Y; D024661:Potassium Channels, Inwardly Rectifying; D011333:Pro-Opiomelanocortin; D011374:Progesterone; D012333:RNA, Messenger; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C577509:Abcc8 protein, rat