Implication of Ornithine Decarboxylase and Polyamines in Pancreatic Growth of Neonatal Rats

Morisset, Jean; Grondin, Gilles

doi:10.1097/00006676-198705000-00009

Cited by 23 publications

(14 citation statements)

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“…Various hormones, such as cholecystokinin and its analogue caerulein, enhance pancreatic polyamine biosynthesis (10,19). On the other hand, specific inhibition of ornithine decarboxylase by ␣-difluoromethylornithine not only prevented the accumulation of putrescine and spermidine but also retarded pancreatic growth (20). Stimula- Fig.…”

Section: Discussionmentioning

confidence: 99%

“…tion of ornithine decarboxylase leads to an accumulation of putrescine associated with the initiation of pancreatic growth, whereas intracellular spermidine accumulation apparently is needed for the maintenance of the growth (10,(19)(20)(21)(22)(23). However, determinations of the exact functions of the polyamines in the pancreas or in any mammalian tissues are only tentative.…”

Section: Discussionmentioning

confidence: 99%

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Activation of polyamine catabolism in transgenic rats induces acute pancreatitis

Alhonen

Parkkinen²,

Keinänen³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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Polyamines are required for optimal growth and function of cells. Regulation of their cellular homeostasis is therefore tightly controlled. The key regulatory enzyme for polyamine catabolism is the spermidine͞spermine N 1 -acetyltransferase (SSAT). Depletion of cellular polyamines has been associated with inhibition of growth and programmed cell death. To investigate the physiological function SSAT, we generated a transgenic rat line overexpressing the SSAT gene under the control of the inducible mouse metallothionein I promoter. Administration of zinc resulted in a marked induction of pancreatic SSAT, overaccumulation of putrescine, and appearance of N 1 -acetylspermidine with extensive depletion of spermidine and spermine in transgenic animals. The activation of pancreatic polyamine catabolism resulted in acute pancreatitis. In nontransgenic animals, an equal dose of zinc did not affect pancreatic polyamine pools, nor did it induce pancreatitis. Acetylated polyamines, products of the SSAT-catalyzed reaction, are metabolized further by the polyamine oxidase (PAO) generating hydrogen peroxide, which might cause or contribute to the pancreatic inflammatory process. Administration of specific PAO inhibitor, MDL72527 [N 1 ,N 2 -bis(2,3-butadienyl)-1,4-butanediamine], however, did not affect the histological score of the pancreatitis. Induction of SSAT by the polyamine analogue N 1 ,N 11 -diethylnorspermine reduced pancreatic polyamines levels only moderately and without signs of organ inflammation. In contrast, the combination of N 1 ,N 11 -diethylnorspermine with MDL72527 dramatically activated SSAT, causing profound depletion of pancreatic polyamines and acute pancreatitis. These results demonstrate that acute induction of SSAT leads to pancreatic inflammation, suggesting that sufficient pools of higher polyamine levels are essential to maintain pancreatic integrity. This inflammatory process is independent of the production of hydrogen peroxide by PAO.I ntracellular polyamine levels are tightly maintained by a number of mechanisms, suggesting their importance for cell function. This polyamine homeostasis is controlled by their biosynthesis, interconversion, catabolism, secretion, and uptake. Polyamine biosynthesis is regulated by the activities of ornithine and S-adenosylmethionine decarboxylases. Overexpression of ornithine decarboxylase in transgenic rodents affected spermatogenesis (1, 2), rendered animals more resistant to chemically or electrically induced seizure activity (3) and to ischemic insults (4), and enhanced skin papilloma formation (5). However, the activation of polyamine biosynthesis caused by overexpression of ornithine decarboxylase did not result in enhanced accumulation of the higher polyamines spermidine and spermine. Polyamine catabolism is controlled by the activity of spermidine͞spermine N 1 -acetyltransferase (SSAT; refs. 6 and 7). The acetylated products are oxidized further by the polyamine oxidase (PAO) to spermidine and putrescine. We recently generated transgenic mouse lines with ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Activation of polyamine catabolism in transgenic rats induces acute pancreatitis

Alhonen

Parkkinen²,

Keinänen³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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“…In addition, EGF also stimulates glycogen synthase activity in a time-and concentra tion-dependent manner in cultured mamma lian cells [28]. 30 Sato/Hiramatsu/Kudo Effects of EGF on Glucose Metabolism…”

Section: Discussionmentioning

confidence: 99%

“…In addi tion, EGF is more potent in the induction of ornithine decarboxylase, the rate-limiting en zyme of polyamine synthesis, than is any oth er hormone that increases during pregnancy, and the effect of EGF is synergistic with that of insulin [9]. EGF also stimulates pancreatic ornithine decarboxylase activity [30]. Poly amines are present in the cells of all tissues and contribute to the growth of the pancreas, especially during the neonatal period [30,31 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Epidermal Growth Factor on Glucose Metabolism in Neonatal Rats

Sato¹,

Hiramatsu²,

Kudo³

1995

Neonatology

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Epidermal growth factor (EGF) may play a key role in fetal growth. We have investigated the effects of EGF on glucose metabolism, the main source of energy during the early neonatal period. When compared to control, EGF treatment increased hepatic glycogen, plasma insulin, and the proportion of B cells in the islets of Langerhans, but decreased the concentration of plasma glucagon. Thus, the insulin-to-glucagon molar ratio in plasma was increased in the EGF-treated group. These data suggest that EGF shifts glucose metabolism from catabolism towards anabolism during the early neonatal period by controlling the pancreatic endocrine system. This effect may help the neonate in adapting to the extrauterine environment after birth.

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“…The role of the very high spermidine content in pancreas is not known, but it may be related to the extremely active protein synthesis going on in this particular tissue. The polyamines seem to be required for pancreatic growth and maturation [68], while their role in the exocrine function of the organ is less obvious [69].…”

Section: Pancreatitismentioning

confidence: 99%

Animal disease models generated by genetic engineering of polyamine metabolism

et al. 2005

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The natural polyamines (putrescine, spermidine and spermine) are aliphatic amines containing two (putrescine), three (spermidine) or four (spermine) primary or secondary amino groups. At physiological pH values, these amino groups are positively charged and hence the polyamines AbstractThe polyamines putrescine, spermidine and spermine are natural components of all living cells. Although their exact cellular functions are still largely unknown, a constant supply of these compounds is required for mammalian cell proliferation to occur. Studies with animals displaying genetically altered polyamine metabolism have shown that polyamines are intimately involved in the development of diverse tumors, putrescine apparently has specific role in skin physiology and neuroprotection and the higher polyamines spermidine and spermine are required for the maintenance of pancreatic integrity and liver regeneration. In the absence of ongoing polyamine biosynthesis, murine embryogenesis does not proceed beyond the blastocyst stage. The last years have also witnessed the appearance of the first reports linking genetically altered polyamine metabolism to human diseases.

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Implication of Ornithine Decarboxylase and Polyamines in Pancreatic Growth of Neonatal Rats

Cited by 23 publications

References 0 publications

Activation of polyamine catabolism in transgenic rats induces acute pancreatitis

Activation of polyamine catabolism in transgenic rats induces acute pancreatitis

Effects of Epidermal Growth Factor on Glucose Metabolism in Neonatal Rats

Animal disease models generated by genetic engineering of polyamine metabolism

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