Abstract
Insulin resistance, a risk factor for the development of type 2 diabetes, has not only been identified in humans, but also in animals. Veal calves often develop insulin resistance and can therefore be a model to study this pathology. Avoiding insulin resistance in veal calves may stimulate efficient use of nutrients for health and growth. We have studied the effect of age and several nutritional modulations (e.g. weaning, short-chain fructo-oligosaccharides supplementation, and partial replacement the lactose by fructose, glucose, glycerol or fat) on the development of insulin resistance. The results showed that insulin sensitivity in calves decreases rapidly with age (from birth on) and remains low thereafter. Nutritional modulations can improve postprandial glucose homeostasis and reduce urinary glucose loss, but will not prevent the development of insulin resistance. The age-related decrease in insulin sensitivity and absence of nutritional effects suggests that the development of insulin resistance is primary related to the ontogenetic development (as calves develop from pre-ruminants to ruminants). Using advanced metabolic profiling several potential biomarkers and metabolic pathways were identified that could be associated with the development of insulin resistance. Multiple alterations were found in the glycerophospholipid and the sphingolipid metabolism. The mechanisms behind the associations are not clear, but disturbances in membrane glycerophospholipid metabolism could influence insulin secretion via alteration of the physico-chemical properties of the membrane. Further application of the metabolic profiling techniques may increase our understanding of the mechanisms underlying the development insulin resistance, also in human.
Original language | English |
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Qualification | Doctor of Philosophy |
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Award date | 19-Nov-2018 |
Place of Publication | [Groningen] |
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Print ISBNs | 978-94-6375-181-0 |
Publication status | Published - 2018 |