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FVB/N mice are hypersensitive to moderate insulin‐induced hypoglycemia while 129X1 mice are completely insensitive
Author(s) -
Berglund Eric D.,
Li Candice Y.,
Lynes Sara E.,
Ayala Julio E.,
Wasserman David H
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.949.8
Subject(s) - hypoglycemia , insulin , medicine , hyperinsulinemia , endocrinology , glucagon , clamp , epinephrine , diabetes mellitus , glucose homeostasis , insulin resistance , mechanical engineering , clamping , engineering
The phenotype of mutant mice is known to differ based on background strain. Insulin‐induced hypoglycemia was used as a metabolic stress to examine the strain‐dependence of the endocrine counter‐regulatory response. Hypoglycemic clamps were done in 5h fasted DBA/2J (DBA), C57BL/6J (B6), FVB/NJ (FVB), and 129X1/SvJ (129X1) mice (n=7–9) surgically implanted with carotid artery and jugular vein catheters 5d prior to study. During the clamp, insulin was infused (20mU/kg/min) and plasma levels increased to ~350 mU/mL in each strain. Hypoglycemia (~45 mg/dL) was maintained via variable glucose infusion rate and glucose turnover was assessed with [3‐ 3 H]glucose. Glucagon (pg/mL) increased by 51±11, 111±21, and 304±40 in DBA, B6, and FVB, but failed to increase in 129X1. Epinephrine (pg/mL) increased by 174±38, 203±36, and 1076±149 in DBA, B6, and FVB, but did not change in 129X1. Hyperinsulinemia suppressed hepatic glucose production in DBA, B6, and 129X1, but failed to do so in FVB due to the greater counter‐regulatory drive. In summary, FVB and 129X1 provide contrasting counter‐regulatory responses during hypoglycemic clamps. These mouse models may be useful in understanding the response to insulin‐induced hypoglycemia and the impairment that frequently occurs in people with diabetes. Supported by DK50277 and DK59637.