title: Antecedent glycemic control reduces severe hypoglycemia-induced neuronal damage in diabetic rats.
abstract: Brain damage due to severe hypoglycemia occurs in insulin-treated people with diabetes. This study tests the hypothesis that chronic insulin therapy that normalizes elevated blood glucose in diabetic rats would be neuroprotective against brain damage induced by an acute episode of severe hypoglycemia. Male Sprague-Dawley rats were split into three groups: 1) control, non-diabetic; 2) STZ-diabetic; and 3) insulin-treated STZ-diabetic. After 3 wk of chronic treatment, unrestrained awake rats underwent acute hyperinsulinemic severe hypoglycemic (10-15 mg/dl) clamps for 1 h. Rats were subsequently analyzed for brain damage and cognitive function. Severe hypoglycemia induced 15-fold more neuronal damage in STZ-diabetic rats compared with nondiabetic rats. Chronic insulin treatment of diabetic rats, which nearly normalized glucose levels, markedly reduced neuronal damage induced by severe hypoglycemia. Fortunately, no cognitive defects associated with the hypoglycemia-induced brain damage were observed in any group. In conclusion, antecedent blood glucose control represents a major modifiable therapeutic intervention that can afford diabetic subjects neuroprotection against severe hypoglycemia-induced brain damage.
authors.affiliation: Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine;
authors.forename: Candace M
authors.initials: CM
authors.lastname: Reno
authors.forename: Tariq
authors.initials: T
authors.lastname: Tanoli
authors.forename: Adam
authors.initials: A
authors.lastname: Bree
authors.forename: Dorit
authors.initials: D
authors.lastname: Daphna-Iken
authors.forename: Chen
authors.initials: C
authors.lastname: Cui
authors.forename: Susan E
authors.initials: SE
authors.lastname: Maloney
authors.forename: David F
authors.initials: DF
authors.lastname: Wozniak
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Fisher
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001927:Brain Diseases / Q000378:metabolism / Q000517:prevention & control*; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D015309:Glucose Clamp Technique; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism; D007003:Hypoglycemia / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D018696:Neuroprotective Agents
keywords: brain damage; diabetes; severe hypoglycemia