title: Fasting time duration modulates the onset of insulin-induced hypoglycemic seizures in mice.
abstract: Fasting (48h) in mice causes resistance to insulin-induced hypoglycemic seizures (IIHS) but in rats fasting (14-16h) predisposes IIHS. So we suspect the duration of fasting may possibly affect the onset of seizures and in this study, we investigated the IIHS by administering 8 Units (U) insulin (INS)/k.g., intraperitoneally to 8 weeks old male C57BL6/J mice.
  
  
  
  The mice were divided into group 1 (non-fasted), group 2 (6h fasted) and group 3 (24h fasted) and we administered the 8U INS. The first behavioral hypoglycemic seizure symptoms such as jump, clonus or barrel rotations considered as seizure onset and we analyzed the blood glucose level (BGL) and serum beta-hydroxybutyrate (BHB) level.
  
  
  
  The time of first seizure onset in group 1 was 109.7±4.3min, group 2 was 46.50±3.9min and group 3 was 165.4±13.26min. The seizure onset time in group 2 was significantly decreased compared to group 1. The seizure onset time in group 3 was significantly increased compared to group 1 and group 2. The decreased BGL after INS administration was correlated with the seizure onset time in group 1 and group 2 but not in group 3. The BHB level in group 3 was significantly higher compared to group 1 and 2.
  
  
  
  Our data show that the fasting time duration significantly modulates the onset of hypoglycemic seizures. The opposite effect of 6h or 24h fasting time duration is likely caused by different BHB levels.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Vigneshwaran
authors.initials: V
authors.lastname: Pitchaimani
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Somasundaram
authors.initials: S
authors.lastname: Arumugam
authors.affiliation: Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Rajarajan Amirthalingam
authors.initials: RA
authors.lastname: Thandavarayan
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Vengadeshprabhu
authors.initials: V
authors.lastname: Karuppagounder
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Mst Rejina
authors.initials: MR
authors.lastname: Afrin
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Remya
authors.initials: R
authors.lastname: Sreedhar
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Meilei
authors.initials: M
authors.lastname: Harima
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Miyashita
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Gastroenterology, Niigata University of Graduate School of Medicine and Dental Sciences, Niigata City 951-8510, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Cardiology, Yamanashi Prefectural Central Hospital, Kofu, Yamanashi 400-8506, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ueno
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan. Electronic address: watanabe@nupals.ac.jp.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D000818:Animals; D001786:Blood Glucose; D004195:Disease Models, Animal; D005215:Fasting / Q000502:physiology*; D007003:Hypoglycemia / Q000401:mortality / Q000503:physiopathology*; D007263:Infusions, Parenteral; D007328:Insulin; D007659:Ketones / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009068:Movement / Q000502:physiology; D012640:Seizures / Q000401:mortality / Q000503:physiopathology*; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007328:Insulin; D007659:Ketones; D020155:3-Hydroxybutyric Acid
keywords: Fasting; Hypoglycemic autonomic failure; Hypoglycemic seizures; Ketone bodies