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    Insulin resistence in adult type-2 diabetic skeletal muscle : the effects of exercise and dietary-protein induced skeletal mucscle plasticity controlling microvascular blood flow and glucose transport : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy (Sport and Exercise Science), Massey University, Wellington, New Zealand
    (Massey University, 2019) Peeters, Wouter
    Introduction: Insulin-stimulated skeletal muscle glucose uptake is impaired in Type-2 Diabetes Mellitus (T2DM). Insulin resistance leads to reduced skeletal muscle microvascular function and insulin signalling. The purpose of the thesis was to evaluate and compare the effect of chronic intake of a novel keratin-derived protein (WDP) and whey protein, in conjunction with exercise training, on glucose homeostasis and skeletal muscle glucose uptake in T2DM. Methods: In a randomized, double-blinded clinical trial, thirty-five men and women with T2DM completed a 14-week exercise intervention but were randomly assigned to ingest either post-exercise and evening supplements of 20 g WDP-whey protein blend (WDP, n = 11), whey protein (WHEY, n = 12) or isocaloric maltodextrin (CON, n = 12). Before and after the intervention, fasting HbA1c and glucose clearance rate (GCR) during a hyperinsulinaemic isoglycaemic clamp were measured. Insulin-stimulated skeletal muscle blood flow and volume were measured during the clamps via near -infrared spectroscopy. Muscle from the m. vastus lateralis was harvested prior to and at 1-h into the clamps to determine skeletal muscle insulin signalling proteins. Results: Substantially bigger improvements in WDP compared to WHEY or CON were found for GCR, insulin-stimulated GLUT4 translocation and insulin-stimulated blood flow. Fasting eNOSser1177/eNOS possibly increased in WDP and WHEY compared to CON. Capillarization improved in all groups with unclear differences between groups. Conclusion: WDP-whey blend ingestion during 14 weeks of exercise training improved skeletal muscle plasticity and some processes involved in insulin-stimulated glucose uptake to a greater magnitude compared to whey protein or an exercise-only group in T2DM. WDP protein holds the potential to be an additional therapy to exercise as a treatment in T2DM.
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    Effect of Highbush blueberry consumption on markers of metabolic syndrome : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Nutritional Science at Massey University, Palmerston North, New Zealand
    (Massey University, 2014) Pranprawit, Araya
    Background : Metabolic syndrome (MS) is becoming a major public health challenge worldwide, and is associated with a higher risk of the development of several chronic diseases including type II diabetes. Being physically active would provide the most effective management for metabolic disorders; however, the use of dietary bioactive compounds from various plants has also been proposed as an alternative approach. A number of experimental studies indicate that Lowbush blueberries may be able to reduce symptoms of MS but the evidence for Highbush blueberries, which are commonly consumed, is scarce and their benefits remain doubtful. Therefore, the primary objective of this thesis was to investigate the effect of selected Highbush blueberries grown in New Zealand on their potential for managing metabolic-related disorders in order to provide further knowledge of the role for bioactive compounds from Highbush blueberries. Method : The selected eight Highbush blueberry cultivars were initially characterised by measuring total phenolic content using a Folin-Ciocalteu procedure; anthocyanin profiles and chlorogenic acid concentration by HPLC; and antioxidant capacity by the ferric reducing antioxidant power (FRAP) and by 2,2, diphenyl-picrylhydrazyl (DPPH) assays (Chapter 3). Further experiments were then carried out to investigate whether these Highbush blueberries possess any activity against measures of MS in vitro. The ability of Highbush blueberries to inhibit α-amylase and α-glucosidase, the enzymes involved in breaking down starch, and their abilities to enhance the growth of beneficial probiotic bacteria, another mechanism associated with improving insulin resistance, were tested in Chapter 4. Finally, the physiological effects of Highbush blueberry consumption on metabolic syndrome biomarkers were assessed in vivo using animal models of diet-induced metabolic syndrome (Chapter 5-7). Results : Our results demonstrated that selected Highbush blueberries grown in New Zealand contained considerable amounts of polyphenolics and total anthocyanins, and exhibited high antioxidant activities, with ‘Burlington’ and ‘Elliott’ cultivars exhibiting the highest total phenolic content (> 3.4 mg GAE/g frozen berries (FB)), total anthocyanins (> 2.2 mg/g FB) and antioxidant capacities (FRAP; > 3.0 mg FeSO4/g FB, DPPH; > 65% inhibition at 5 mg FB). Further in vitro experiments supported the ability of these blueberries to inhibit α-amylase (10-40% inhibition at 20 mg FB) and α-glucosidase (10-50% inhibition at 25 mg FB); additionally, some blueberry cultivars possessed the ability to increase the growth of the probiotic bacteria Lactobaccillus acidophilus by more than 0.5 log10 CFU/mL. However, the extent of these benefits was not closely correlated with total phenolic content (R2 < 0.27), total anthocyanins (R2 < 0.23), or antioxidant capacities (FRAP; R2 < 0.42, DPPH; R2 < 0.24) across all genotypes, indicating that these anti-metabolic syndrome abilities were not simply due to the total bioactives or antioxidant capacities presented in the berries. ‘Burlington’ and ‘Bluecrop’, which exhibited strong enzyme inhibition as well as enhanced beneficial probiotic bacterial growth but contained different components of individual anthocyanins, were chosen for further testing in vivo. Rats fed a high-fat-high-sugar diet plus 1% freeze-dried whole blueberries (both cultivars) for 8 weeks showed signs of improvement of glucose tolerance and exhibited between 30 and 36% decrease in the degree of insulin resistance (HOMA-IR) as compared to the controls. The blueberries also showed a trend to increase the growth of beneficial bacteria, Lactobacillus spp. (P = 0.20) and Bifidobacterium spp. (P = 0.15), in the rats’ caecal content. However, no reduction in body weight or fat accumulation was observed with blueberry supplementation. There were no significant differences (P > 0.05) in the abilities of ‘Burlington’ and ‘Bluecrop’ to modulate any metabolic biomarkers assessed in vivo. Conclusion : Inclusion of the blueberries into the diet showed promise for management of some markers of metabolic syndrome, in particular the improvement of insulin sensitivity and glucose tolerance. The results of these studies shed some light on the beneficial effect of selected NZ Highbush blueberries against insulin resistance associated with metabolic syndrome.
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    The role of vitamin D in metabolism and bone health : a thesis presented in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Nutritional Science at Massey University, Albany, New Zealand
    (Massey University, 2009) von Hurst, Pamela Ruth
    Background Hypovitaminosis D is becoming recognised as an emerging threat to health, even in countries like New Zealand which enjoy plentiful sunshine. The evidence for a role for vitamin D deficiency in the aetiology of a plethora of diseases continues to accumulate, including type 2 diabetes, and the preceding insulin resistance. Objectives The primary objective of the Surya Study was to investigate the effect of improved vitamin D status (through supplementation) on insulin resistance. The secondary objectives were to investigate the vitamin D status and bone mineral density of South Asian women living in New Zealand, and to investigate the effect of vitamin D supplementation on bone turnover as measured by biochemical markers of bone resorption and formation. Method Women of South Asian origin, ≥20 years old, living in Auckland (n = 235) were recruited for the study. All were asked to complete a 4-day food diary, invited to have a bone scan, and were screened for entry into the intervention phase which required insulin resistance (HOMA-IR >1.93) and serum 25(OH)D < 50 nmol/L. Eighty-one completed a 6-month randomised controlled trial with 4000 IU vitamin D3 (n = 42) or placebo (n = 39). Primary endpoint measures included insulin resistance, insulin sensitivity (HOMA2%S), fasting C-peptide and markers of bone turnover, osteocalcin (OC) and collagen C-telopeptide (CTX). Ninety-one of the 239 had a bone scan and bone mineral density (BMD) was measured in the proximal femur and lumbar spine. Results Adequate serum 25(OH)D concentrations (>50 nmol/L) were observed in only 16% of subjects screened. Median (25th, 75th percentile) serum 25(OH)D increased significantly from 21 (11,40) to 75 (55,84) nmol/L with supplementation. Significant improvements were seen in insulin sensitivity and insulin resistance (P = 0·003, P = 0·02 respectively), and circulating serum insulin decreased (P = 0·02) with supplementation compared to placebo. There was no change in C-peptide with supplementation. Insulin resistance was most improved when endpoint serum 25(OH)D =80 nmol/L. In post-menopausal women OC and CTX levels increased in the placebo arm but CTX decreased from 0.39±0.15 to 0.36±0.17 (P = 0.012) with supplementation. Osteoporosis (T score <-2.5) was present in 32% of postmenopausal, and 3% of premenopausal women. Women 20 – 29 years (n=10) had very low BMD, calcium intake and serum 25(OH)D Conclusions Improving vitamin D status in insulin resistant women resulted in improved insulin resistance and sensitivity but no change in insulin secretion. Optimal 25(OH)D concentrations for reducing insulin resistance were shown to be ≥80 nmol/L. The prevalence of low 25(OH)D concentrations in this population was alarmingly high, especially in younger women. In post-menopausal women, vitamin D supplementation appeared to ameliorate increased bone turnover attributed to oestrogen deficiency.