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Title: A biophysical approach to the investigation of the properties of insulin and its receptor.
Author: Horuk, H.
Awarding Body: Birkbeck (University of London)
Current Institution: Birkbeck (University of London)
Date of Award: 1980
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This thesis describes the properties of two hystricomorph rodent insulins, those of the casiragua (Proechimys guairae) and of the porcupine (Hystrix cristata). Studies of two bovine insulin analogues DAA and triphthaloyl insulins are also presented. Casiragua insulin has been extracted and purified and its primary structure determined. The association properties of casiragua insulin have been investigated by ultracentrifuge studies and these show that it sediments as a monomer even at high hormone concentration. Zinc binding studies reveal that casiragua and porcupine insulins are unable to bind zinc ions. Circular dichroism studies fully confirm the failure of casiragua and porcupine insulins to associate and also reveal changes in conformation compared with bovine insulin. The biological properties of the insulins have been examined by in vivo and in vitro bioassays and by receptor binding assays on liver plasma membranes. These studies reveal that casiragua and porcupine insulins have a low potency in all mammalian tissues. Triphthaloyl insulin is shown to be almost fully potent in hystricomorph tissues yet of low activity in other mammals. On the basis of these results it is suggested that hystricomorph insulin receptors have undergone change. It is proposed that this, together with changes in the structure of their insulins, has resulted in a dimunition of the hypoglycaemic properties of these insulins and a possible enhancement of other properties: growth promoting properties for example. The possible contribution of the B22-A21 ion pair to the stability of insulin has been investigated by studieswith DAA insulin. Evidence is presented which suggests that the ion pair is not as important in maintaining the hormone in an active conformation as was previously thought.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Biophysics Biophysics