Continuous carbachol infusion promotes peripheral cell proliferation and mimics vagus hyperactivity in a rat model of hypothalamic obesity

Yoshimura, Ryoichi; Omori, Hiroshi; Somekawa, Shingo; Osaka, Toshimasa; Ito, Ryo; Inoue, Shuji; Endo, Yasuhisa

doi:10.2220/biomedres.27.81

Cited by 11 publications

(11 citation statements)

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“…1). This is quite similar to data from the VMH-lesioned rats [8], in addition to duodenal and pancreatic cell proliferation being induced to a similar degree in VMH-lesioned rats [13]. This notion suggests that the peripheral proliferation in this animal model can occur independently from overweight, hyperinsulinemia, or hyperglycemia.…”

Section: Discussionsupporting

confidence: 88%

“…Both subdiaphragmic vagus nerves running along the lower esophagus were bilaterally cut, as previously reported [13,23].…”

Section: Animalsmentioning

confidence: 99%

“…The ACh agonist Cch or saline as the control was continuously delivered for 3 days by an osmotic minipump (Alzet, model 1003D; Alza, Palo Alto, CA) implanted into the abdominal cavity of vagotomized rats [13]. The minipump was implanted 3 days after the vagotomy.…”

Section: Animalsmentioning

confidence: 99%

“…The available data [13] suggest that cholinergic stimulus promotes pancreatic and duodenal cell proliferation to a degree comparable to that of VMH lesions.…”

mentioning

confidence: 93%

“…We have demonstrated that cell proliferation increases in the B-cells of the pancreatic islets of Langerhans and in the epithelial cells of the duodenal crypts after carbachol (Cch; ACh agonist) infusion, and also after VMH lesion development [13]. The available data [13] suggest that cholinergic stimulus promotes pancreatic and duodenal cell proliferation to a degree comparable to that of VMH lesions.…”

mentioning

confidence: 97%

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Carbachol Induces Hepatocyte Proliferation, but Only in the Presence of Hepatic Nonparenchymal Cells

et al. 2007

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Vagal hyperactivity correlates with enhanced DNA synthesis and cell proliferation in the peripheral tissues of ventromedial hypothalamic (VMH)-lesioned rats. The infusion of an ACh receptor agonist, carbachol (Cch), induces rat duodenal and pancreatic cell proliferation to a degree comparable to the VMH lesions. Whereas the VMH lesions also induce the proliferation of hepatic cells, it is unclear whether Cch can also do this. Here we attempted to clarify the mechanism of hepatic cell proliferation induction by cholinergic stimulation. First, hepatic cell proliferation was examined in rats previously vagotomized and intraperitoneally administered with Cch via an osmotic minipump. Second, the sera from the Cch-infused rats were examined for a proliferative effect on isolated hepatic cells. And last, the effect of the presence of hepatic nonparenchymal cells (NPCs) on the proliferation of the cultured hepatocytes treated with Cch was investigated. Immunohistochemistry for proliferating cell nuclear antigen (PCNA) showed that the 3-day Cch infusion significantly increased the number of PCNA-immunoreactive cells in the liver. Moreover, the sera from the Cch-infused rats increased the number of PCNA-immunoreactive hepatocytes in culture. However, Cch alone did not induce proliferation in monocultured hepatocytes. When compared with the monoculture of hepatocytes, the coculture of those with hepatic NPCs resulted in enhanced PCNA immunoreactivity after a 4-day treatment with 3 mM Cch. These findings suggest that ACh induces hepatocyte proliferation, which is mediated by unidentified humoral factor(s) possibly secreted from hepatic NPCs, and that it also participates in liver hypertrophy in the VMH-lesioned animals.Key words: acetylcholine, cell proliferation, liver, autonomic nervous system, obesity.The mechanism of obesity formation is quite complex.Because the causal relation with a serious disease such as diabetes is suggested in obesity, diversified analyses of the mechanism of the obesity formation are needed. As for the cause, besides overeating and physical inactivity, inheritance, medicine, and the hypothalamus are possible reasons.Neural obesity is also called hypothalamic obesity and includes the obesity induced by the lesions of the ventromedial hypothalamus (VMH) [1]. The VMH is involved in the autonomic regulation of feeding, sugar metabolism in the liver, and endocrine secretion of the pancreas [2]. Feeding decreases if VMH is electrically stimulated, whereas it increases if VMH is injured. Moreover, feeding increases if the lateral hypothalamus (LH) is activated and reduces if LH is suppressed. The VMH and LH are reciprocally regulated to each other; therefore it has been thought for a long time that the primary cause of neural obesity induced by VMH lesions is an overeating from hunger.It was reported in the 1960s, however, that obesity developed even if overeating was controlled by a pair-feeding experiment. Enhanced insulin secretion, which may result in hyperinsulinemia, arises in VMH-lesio...

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Section: Discussionsupporting

confidence: 88%

“…Both subdiaphragmic vagus nerves running along the lower esophagus were bilaterally cut, as previously reported [13,23].…”

Section: Animalsmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

“…The available data [13] suggest that cholinergic stimulus promotes pancreatic and duodenal cell proliferation to a degree comparable to that of VMH lesions.…”

mentioning

confidence: 93%

mentioning

confidence: 97%

See 3 more Smart Citations