The Effects of Protein on Gastrointestinal Responses, Associated with Energy Intake and Blood Glucose Regulation – a Management Strategy for Obesity and Type 2 Diabetes

Abstract

The research reported in this thesis investigated whether dietary AAs, including the BCAAs, had the potential to reduce energy intake and/or postprandial blood glucose in health and T2D, by stimulating gastrointestinal functions (gut hormone release and gastric emptying). If this proved to be the case it would support the goal of identifying nutrient-based treatment approaches for obesity and T2D. The key findings of the studies are: 1. Following whey protein drinks (30 and 70 g), plasma concentrations of specific AAs, increased in a ‘load-of-protein-dependent’ manner, and there were strong relationships between plasma CCK, GLP-1, insulin and glucagon with the BCAAs, methionine, tryptophan, aspartic acid and tyrosine (Chapter 2). Ghrelin and energy intake correlated inversely, but only weakly, with AAs. Blood glucose did not correlate with any AAs, possibly because the drinks contained no carbohydrate, and any effect of insulin was counteracted by glucagon. 2. Intraduodenal infusion of valine (3.3 and 9.9 g), had no effect on antral, pyloric or duodenal pressures, plasma CCK, blood glucose, appetite perceptions or energy intake (Chapter 3). These results suggest that valine, unlike leucine, as shown in a previous study, does not have an energy intake-suppressant effect. 3. Leucine and isoleucine, but not valine, administered intragastrically (10 g), reduced the blood glucose response to a mixed-nutrient drink (Chapter 4). Leucine and isoleucine slowed early gastric emptying of the drink, while neither AA affected early (t = 0-30 min) postprandial C-peptide. Valine did not stimulate C-peptide, but stimulated glucagon markedly prior to drink ingestion. The lack of effect of valine to reduce blood glucose despite slowing gastric emptying may have reflected the simulation of glucagon. 4. In contrast to previous findings in healthy individuals, leucine and isoleucine, administered intragastrically (10 g), did not reduce the blood glucose response to a mixed-nutrient drink, in T2D (Chapter 5). Both AAs stimulated insulin before and after the drink. Isoleucine simulated glucagon before and after the drink, while leucine tended to stimulate glucagon, before the drink. Neither AA slowed gastric emptying. It is uncertain why insulin stimulation by leucine and isoleucine was not associated with glucose lowering, but the stimulation of glucagon, presumably by circulating AAs, is likely to be important. In conclusion, the research presented in this thesis has established that AAs vary widely in their effects on energy intake and postprandial blood glucose in health and T2D. Leucine and isoleucine, lower blood glucose, in part mediated by the slowing of gastric emptying, while valine does not have an effect on energy intake or blood glucose. Surprisingly, leucine and isoleucine did not lower the blood glucose response to a mixed-nutrient drink in T2D. Accordingly, these observations indicate that the underlying mechanisms, mediating the effects of leucine and isoleucine, when given in isolation, on blood glucose, are differential and complex, particularly in relation to comparative effects of leucine and isoleucine in health and T2D. The conditions under which the BCAAs may be more effective (i.e. in combination), to reduce energy intake and postprandial blood glucose, warrant further evaluation.