Nicotinamide : implications for the prevention and treatment of Type I diabetes
Nicotinamide : implications for the prevention and treatment of Type I diabetes
Nicotinamide, a vitamin B derivative, has been reported to protect against the development of diabetes in animal models. It is also widely believed that nicotinamide has no toxic effects. Nicotinamide is now known to be of little or no benefit in diabetics with established disease. However, on the basis of findings from limited animal studies, prevention trials are currently in progress in which children who are thought to be at high risk of developing Type I diabetes are treated prophylactically with nicotinamide.
In this thesis, the effect of nicotinamide was investigated in the pancreatectomy animal model of diabetes, to establish the efficacy of oral nicotinamide compared to the known efficacy of intra-peritoneal administration of nicotinamide on improving glucose tolerance. Furthermore the pharmacokinetics of nicotinamide in both man and rodent were studied in order to establish whether differences exist in circulating serum levels of nicotinamide. The dose used in the rodent was at the level known to protect against the onset of diabetes, and was twentyfold higher than used in man, calculated as the dose currently used in the human trials.
From these studies, high doses of nicotinamide were shown to cause a significant inhibition in vertical bone growth in the rat and furthermore the efficacy of oral nicotinamide was ambiguous. In addition, the pharmacokinetics of nicotinamide in humans and rats revealed that the serum levels of nicotinamide achieved in the rat were far greater than the levels achieved in man.
This thesis also investigated the in vitro effect of nicotinamide on insulin release and islet cell replication in isolated islets maintained in tissue culture. These studies showed that nicotinamide caused a significant increase in insulin release, which was dependent on the presence of glucose, but there was no effect of nicotinamide on cell replication.
This thesis demonstrates that the serum levels of nicotinamide achieved in man are far below those recorded in rodents and also below the levels required to reproduce any of the effects previously demonstrated in vitro.
University of Southampton
Petley, Anne Mary
c607f311-b3e1-4ccc-9d5a-de0f73d52df2
1993
Petley, Anne Mary
c607f311-b3e1-4ccc-9d5a-de0f73d52df2
Petley, Anne Mary
(1993)
Nicotinamide : implications for the prevention and treatment of Type I diabetes.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Nicotinamide, a vitamin B derivative, has been reported to protect against the development of diabetes in animal models. It is also widely believed that nicotinamide has no toxic effects. Nicotinamide is now known to be of little or no benefit in diabetics with established disease. However, on the basis of findings from limited animal studies, prevention trials are currently in progress in which children who are thought to be at high risk of developing Type I diabetes are treated prophylactically with nicotinamide.
In this thesis, the effect of nicotinamide was investigated in the pancreatectomy animal model of diabetes, to establish the efficacy of oral nicotinamide compared to the known efficacy of intra-peritoneal administration of nicotinamide on improving glucose tolerance. Furthermore the pharmacokinetics of nicotinamide in both man and rodent were studied in order to establish whether differences exist in circulating serum levels of nicotinamide. The dose used in the rodent was at the level known to protect against the onset of diabetes, and was twentyfold higher than used in man, calculated as the dose currently used in the human trials.
From these studies, high doses of nicotinamide were shown to cause a significant inhibition in vertical bone growth in the rat and furthermore the efficacy of oral nicotinamide was ambiguous. In addition, the pharmacokinetics of nicotinamide in humans and rats revealed that the serum levels of nicotinamide achieved in the rat were far greater than the levels achieved in man.
This thesis also investigated the in vitro effect of nicotinamide on insulin release and islet cell replication in isolated islets maintained in tissue culture. These studies showed that nicotinamide caused a significant increase in insulin release, which was dependent on the presence of glucose, but there was no effect of nicotinamide on cell replication.
This thesis demonstrates that the serum levels of nicotinamide achieved in man are far below those recorded in rodents and also below the levels required to reproduce any of the effects previously demonstrated in vitro.
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Published date: 1993
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Local EPrints ID: 462534
URI: http://eprints.soton.ac.uk/id/eprint/462534
PURE UUID: 6438f0b5-ecd7-4953-b83f-db28e9627055
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Date deposited: 04 Jul 2022 19:16
Last modified: 23 Jul 2022 01:07
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Author:
Anne Mary Petley
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