Ventromedial hypothalamic lesion-induced vagal hyperactivity stimulates rat pancreatic cell proliferation.
OBJECTIVE
Ventromedial hypothalamic (VMH) lesions cause an increase in DNA content in the rat pancreas. This study examined the role of cell proliferation in the mitotic response of the rat pancreas after VMH lesion formation.


METHODS
Alterations in rat pancreatic DNA content, DNA synthesis, and labeling indices using antiproliferation cell nuclear antigen molecular antibody were measured 0,1,3, and 7 days after VMH lesion formation. Additionally, the effects of vagotomy, atropine, or anti-insulin antibody on VMH lesion-induced alterations in DNA synthesis were examined. Pancreatic samples were also treated with double immunostaining: first for PCNA and then for insulin, glucagon, and somatostatin.


RESULTS
Pancreatic weight, DNA content, and DNA synthesis increased in animals receiving VMH lesions. Proliferation was primarily observed in islet B and acinar cells beginning 1 day after VMH lesion formation, reaching a maximum rate after 3 days. VMH lesion-induced stimulation of DNA synthesis was completely inhibited by vagotomy or atropine administration but not by anti-insulin antibody.


CONCLUSIONS
Vagal hyperactivity produced by VMH lesions stimulated cell proliferation of rat pancreatic islet B and acinar cells primarily through a cholinergic receptor mechanism.
Kiba
T
T
Third Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Tanaka
K
K
Numata
K
K
Hoshino
M
M
Misugi
K
K
Inoue
S
S
D000704:Analysis of Variance; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D007330:Insulin Antibodies / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010276:Parasympatholytics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014628:Vagotomy; D014630:Vagus Nerve / Q000503:physiopathology*; D014697:Ventromedial Hypothalamic Nucleus / Q000473:pathology / Q000601:surgery*
D007328:Insulin; D007330:Insulin Antibodies; D010276:Parasympatholytics; D001285:Atropine; D004247:DNA