title: Reduced carnitine level causes death from hypoglycemia: possible involvement of suppression of hypothalamic orexin expression during weaning period.
abstract: The mechanism of onset of hypoglycemia in patients with carnitine deficiency has yet to be determined. Using mice with systemic carnitine deficiency (JVS mice), we examined this mechanism, focusing on the weaning period (days 14-28 postpartum). For normal mice, the survival rate was 100%, and no hypoglycemia was observed at all. Gastric lactose began to decrease on day 17, and cellulose increased sharply in amount thereafter. For JVS mice, the survival rate was 77% on day 14 and 28% on day 28. From day 21 on, hypoglycemia was noted. Gastric lactose had disappeared almost completely by day 17, and cellulose was almost undetectable from days 14 to 28. Expression of orexin mRNA in the hypothalamus did not differ between JVS and normal mice on day 14, but was suppressed in JVS mice on days 21 and 28. When JVS mice were fed a carnitine-rich diet, suppression of expression of orexin mRNA in hypothalamus was eliminated, and on day 28 lactose and cellulose were detected in the stomach without hypoglycemia. In conclusion, the suppression of the expression of orexin in the hypothalamus during the weaning period may be involved in the marked anorexia in JVS mice, which eventually leads to death from hypoglycemia.
authors.affiliation: Department of Clinical Biology and Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Kuwajima
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Fujihara
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Sei
authors.forename: Asako
authors.initials: A
authors.lastname: Umehara
authors.forename: Masako
authors.initials: M
authors.lastname: Sei
authors.forename: Tomi T
authors.initials: TT
authors.lastname: Tsuda
authors.forename: Akiko
authors.initials: A
authors.lastname: Sukeno
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Okamoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Inubushi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ueta
authors.forename: Toshio
authors.initials: T
authors.lastname: Doi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kido
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism*; D002331:Carnitine / Q000008:administration & dosage / Q000097:blood* / Q000172:deficiency*; D002482:Cellulose / Q000008:administration & dosage; D003624:Darkness; D005260:Female; D007003:Hypoglycemia / Q000097:blood* / Q000235:genetics; D007031:Hypothalamus / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D007785:Lactose / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009478:Neuropeptide Y / Q000096:biosynthesis / Q000235:genetics; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D009693:Nucleic Acid Hybridization; D000068797:Orexins; D011247:Pregnancy; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000235:genetics; D013047:Specific Pathogen-Free Organisms
chemical_list: D001786:Blood Glucose; D047908:Intracellular Signaling Peptides and Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D000068797:Orexins; D011333:Pro-Opiomelanocortin; D002482:Cellulose; D007785:Lactose; D002331:Carnitine; D020155:3-Hydroxybutyric Acid