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Estrogen may protect female Akita mice against development of type I diabetes and parasympathetic dysfunction of the heart (680.16)
Author(s) -
Jin Hongwei,
Georgescu Serban,
Naggar Jack,
Welzig Michael,
Aronovitz Mark,
Zhang Yali,
Park HoJin,
Galper Jonas
Publication year - 2014
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.28.1_supplement.680.16
Subject(s) - medicine , endocrinology , polyuria , polydipsia , ovariectomized rat , type 2 diabetes , estrogen , diabetes mellitus
Male Akita mouse harboring a mutation in the Ins‐2 gene, is an established animal model for the secondary effects of type I diabetes. Beginning around 3‐4 weeks of age male Akita mice develop marked hyperglycemia, hypoinsulinemia, polydipsia and polyuria. Female Akita mice develop a moderate hyperglycemia after sexual maturation. Ovariectomized (Ovx) female Akita animals implanted with a placebo (P) or 17β‐estradiol (E 2 ) pellet were compared with the Sham‐operated female Akitas (Sham) or wild‐type (WT) mice. After 13 weeks, blood glucose increased from 268±24 mg/dl in Sham to 536±27 mg/dl in Ovx+P (mean±SEM, p<0.01) while decreasing significantly in Ovx+E 2 to 125±5 mg/dl, compared to the WT (130±4 mg/dl). Compared with Sham, the Ovx+P group demonstrated increased polydipsia, glycosuria and proteinuria which disappeared completely in the Ovx+E 2 group. Furthermore, Ovx+P diabetic mice demonstrated a significant decrease in the negative chronotropic response to carbamylcholine when compared with WT and Sham animals, as characterized by a smaller drop in the response to carbamylcholine (309±14 beats in Ovx+P vs. 406±11 beats in WT and 359±17 beats in Sham; p<0.01) and a decreased duration of bradycardia (4.9±0.5 min. in Ovx+P vs. 26.4±3.8 min. in WT and 17.4±2.5 min. in Sham; p<0.05). The pancreas of female Akita mice showed a reduced islet count and a decreased mean islet area, which could be reversed by estrogen. Thus estrogen may protect female Akita mice against development of the diabetic phenotype and the parasympathetic dysfunction of the heart. This animal model might be used to investigate gender specific effects of diabetes in the cardiovascular system. Grant Funding Source : NIH