Heywood, Wendy Elizabeth;
(2002)
The effect of a maternal low protein diet on pancreatic glucokinase activity.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The work presented in this thesis provides evidence that a maternal low protein (LP) diet during gestation and lactation periods in rats 'programs' pancreatic β-cell glucokinase (GK) the glucose sensor and glucose induced insulin secretion response in newborn, suckling and adult offspring. Pregnant female rats were divided into 3 groups, group A (20%) was kept on a normal protein diet, group B on a LP (6[percent]) diet during pregnancy and lactation and group C on a LP diet during pregnancy and a normal protein diet during lactation. The glucose- induced total insulin secretion response and peak insulin secretion was markedly reduced in group B newborn and 3-week old suckling pups compared with group A controls which is a result of poor nutrition. The insulin secretion also showed an altered secretory response in group B adults and group C 3- week old and adult stage pups compared with group A. The GK protein levels were reduced in newborn, 3-week old pups and adult rats from both group B and C. The GK enzyme exhibited interesting changes in enzyme activity to convert glucose to glucose-6-phosphate particularly in the kinetic reaction parameters pertaining to the enzymes affinity for glucose (Km values) and maximal reaction velocity (Vmax). Poor nutrition reduced GK protein enzyme activity and Km values. The prenatal and postnatal LP diet appears to have a permanent programming effect by increasing the GK affinity for glucose and decreasing the reaction velocity indicating that the critical period of programming of GK's function is after birth during the postnatal weaning period since the adult offspring of group B when fed a normal protein diet showed no reversal in the Km values of the enzyme. Similar experiments on adult offspring of group C which were fed a normal protein diet during weaning and after showed normalisation of the GK Km values for glucose but still exhibited a permanent reduction in Vmax. In conclusion low protein diets during both pregnancy and weaning have immediate and sustained irreversible effects on glucose homeostatic mechanisms of a mother's offspring. Fetal and early life infantile nutrition programs pancreatic β-cell function, with poor nutrition predisposing to diabetes in later life.
Type: | Thesis (Doctoral) |
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Qualification: | Ph.D |
Title: | The effect of a maternal low protein diet on pancreatic glucokinase activity |
Open access status: | An open access version is available from UCL Discovery |
Language: | English |
Additional information: | Thesis digitised by ProQuest. |
Keywords: | Biological sciences; Health and environmental sciences; Low protein diet |
URI: | https://discovery.ucl.ac.uk/id/eprint/10103667 |




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