title: Ischemic hippocampal cell death induces glucose dysregulation by attenuating glucose-stimulated insulin secretion which is exacerbated by a high fat diet.
abstract: OBJECTIVE
  Diabetes increases the chances of stroke and the stroke itself is thought to induce hyperglycemia and diabetes. However, this latter contention remains uncorroborated. We investigated whether ischemic hippocampal neuronal cell death induces glucose dysregulation by modulating insulin resistance, glucose-stimulated insulin secretion, and β-cell mass in Mongolian gerbils fed either a high fat or low fat diet.
  
  
  METHODS
  Gerbils were subjected to either an occlusion of the bilateral common carotid arteries for 8 mins to render them ischemic, or a sham operation. Ischemic gerbils were fed either an 11% fat diet (LFD) or a 40% fat diet (HFD) for 7, 14 or 28 days.
  
  
  RESULTS
  Artery occlusion resulted in a 70% or greater initial reduction in hippocampal CA1 neurons and only HFD decreased the percentage of CA1 neurons as the ischemic periods became longer. Oral glucose tolerance test (OGTT) results revealed that ischemia induced glucose intolerance, and longer ischemic periods and HFD exacerbated this glucose intolerance in ischemic gerbils. Insulin secretion during the OGTT was lower in ischemic gerbils than sham gerbils and the decrease was greatest in the 28 day-HFD among all the groups. Insulin resistance was elevated the most in 28 day-HFD ischemic gerbils. There was a progressive loss of pancreatic β-cell mass as the post-ischemic time period increased as consequence of HFD; the decrease being caused by increased apoptosis. This increase in apoptosis was partly associated with increased serum levels of IL-1β, TNF-α and non-esterified fatty acids.
  
  
  CONCLUSIONS
  Hippocampal neuronal cell death deteriorates glucose homeostasis initially through the modulation of insulin secretion and also causes a decrease in β-cell mass while HFD negatively impacts glucose regulation.
authors.affiliation: Dept. of Food & Nutrition, College of Natural Science, Obesity/Diabetes Research Institutes, Hoseo University, 165 Sechul-Ri, BaeBang-Yup, Asan-Si, ChungNam-Do, South Korea. smpark@hoseo.edu
authors.forename: Sunmin
authors.initials: S
authors.lastname: Park
authors.forename: Da Sol
authors.initials: DS
authors.lastname: Kim
authors.forename: Sunna
authors.initials: S
authors.lastname: Kang
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Kwon
mesh_terms: D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D016923:Cell Death / Q000502:physiology*; D018752:Diet, Fat-Restricted; D004041:Dietary Fats / Q000494:pharmacology*; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005849:Gerbillinae; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D009474:Neurons / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D053583:Interleukin-1beta; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose