Gastric emptying in humans; carbohydrate ingestion, gastrointestinal hormones and genetic variation

Yau, Mo Wah Adora (2014) Gastric emptying in humans; carbohydrate ingestion, gastrointestinal hormones and genetic variation. Doctoral thesis (PhD), Manchester Metropolitan University.

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Abstract

The prevalence of overweight and obesity continues to rise substantially across the world. It is the leading preventable cause of death worldwide and is associated with a large number of comorbidities that present a perpetual burden on healthcare costs. Much of the recent work to understand and address the problem of obesity has focused on the role of gastrointestinal hormones on the regulation of appetite, satiety, and food intake, and how interventions such as physical activity and exercise can affect the secretion of these hormones. However, the gastrointestinal system and the role of gastric emptying are often overlooked. The aim of this thesis was to enhance understanding of the physiology and regulation of gastric emptying and its interactions with carbohydrates. This will help in the development of novel non-pharmacological dietary interventions or foods that can modulate appetite and energy intake. A series of studies on human volunteers are presented in this thesis. Firstly, the gastric emptying rate of different 6% simple sugar solutions (water control, fructose, glucose, sucrose, 50:50 fructose and glucose) and gut hormone responses of circulating acylated ghrelin, active glucagon like peptide-1 (GLP-1), glucose dependent insulinotropic polypeptide (GIP) and insulin were investigated. Hepatic metabolism and function in response to the different simple sugar solutions were also examined. The time of maximal gastric emptying rate (Tlag) differed significantly between between sucrose and glucose solutions. Differences in insulin and GIP responses between fructose containing solutions and glucose only solutions were also seen. No differences in hepatic metabolism measures or function were observed following the intake of 36 g of the various test sugars. However, lactate production was significantly greater for fructose containing solutions. Following on from these results, the effect of increased dietary fructose intake on gastric emptying rate of glucose and fructose was investigated. Three days supplementation with 120g/d fructose resulted in acceleration of gastric emptying rate of a fructose but not a glucose solution. No significant differences in the circulating concentration of gastrointestinal hormones, but subtle differences in responses over time were suggested which may explain the specific monosaccharide adaptations of gastric emptying. Further work is required to confirm this and to investigate the longevity and reversibility of the gastrointestinal adaptation and the mechanism involved. Lastly, several tagging single nucleotide polymorphisms (SNP) of the GLP-1 receptor gene were associated with gastric emptying rate. Further work is required on the regions identified to pinpoint the exact SNP or SNPs responsible.