Appetite regulation by carbohydrate: role of blood glucose and gastrointestinal hormones J. H. LAVIN, G. WITTERT, W.-M. SUN, M. HOROWITZ, J. E. MORLEY, AND N. W. READ Department of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, Australia 5000; Centre for Human Nutrition, Northern General Hospital, Shefield S5 7AU, United Kingdom; and Division of Geriatric Medicine, St. Louis University Health Sciences Center, St. Louis, Missouri 63104 Lavin, J. H., G. Wittert, W.-M. Sun, M. Horowitz, J. E. Morley, and N. W. Read. Appetite regulation by carbohy- drate: role of blood glucose and gastrointestinal hormones. Am. J. Physiol. 271 (Endocrinol. Metab. 34): E209-E214, 1996.-To investigate the mechanisms by which intestinal carbohydrate affects eating behavior, seven fasted, healthy male volunteers received intraduodenal infusions of glucose or saline over a 90-min period while blood glucose levels were matched by use of intravenous glucose and saline infusions. A second study examined the effect of intraduodenal glucose on eating behavior when the gastrointestinal hormone response was inhibited by intravenous octreotide. Intravenous glucose infusion did not affect hunger or satiety. In contrast, intraduo- denal infusion of glucose suppressed hunger, increased full- ness and satiety ratings, reduced energy intake, and resulted in higher plasma insulin responses compared with the intra- venous glucose infusion. Octreotide abolished the plasma insulin response to intraduodenal glucose and reversed the changes in ratings and eating behavior. This study has shown that the effects of intestinal glucose on appetite are not mediated via an increase in blood glucose but are likely to reflect small intestinal stimulation of release of either insulin or intestinal incretins. satiety; small intestine; insulin; gastric inhibitory polypep- tide; somatostatin INGESTION OF CARBOHYDRATE has a powerful effect on short-term satiety (22,23) that may be greater than the effect of fat (5, 8, 30). The mechanisms by which carbohydrate influences satiety are not fully under- stood. For many years postabsorptive mechanisms were thought to be primarily responsible. The gluco- static theory of hunger and satiety proposed that hypothalamic glucoreceptors respond to the level of glucose in the blood: a fall in blood glucose signals hunger, whereas an increase in blood glucose concentra- tions activates hypothalamic satiety areas and sup- presses eating (16). This was supported by further studies which indicated that intravenous infusion of glucose increased electrical activity in the ventrome- dial satiety areas and decreased activity in lateral feeding areas (4). Russek (24) later suggested that it was in fact hepatic glucoreceptors that conveyed infor- mation to the central nervous system in the control of eating behavior, with support coming from the observa- tion that intraportal infusion of glucose suppressed feeding in dogs (25). However, studies in animals have failed to show any inhibition of feeding by even large intravenous glucose loads (1, 2, 12), suggesting that increases in blood glucose concentration are not di- rectly involved in the signaling of satiety. The importance of intestinal glucose receptors in the control of eating behavior has been emphasized by a recent study from our laboratory which showed that satiety was increased and hunger decreased when the intestinal absorption of glucose was slowed by the addition of guar gum in the absence of any change in gastric emptying (13). We concluded that the increased contact of glucose with small intestinal receptors plays an important role in the satiating effect of carbohy- drate. The observation that addition of guar gum did not delay gastric emptying ruled out any differential effect of gastric distension on satiety (27). The presence of glucose in the small intestine stimu- lates vagal activity (17) and releases hormones that elevate plasma insulin (10). Both actions could affect appetite. Vagotomy abolishes the satiating effects of isotonic glucose infused into the duodenum of rabbits (20). The dat a on insulin are contradictory. Animal studies carried out in the absence of hypoglycemia have shown that raised circulating insulin levels are associ- ated with reduced food intake (19, 31, 33), whereas, in humans, exogenous increases in insulin have been reported to stimulate appetite independent of changes in blood glucose levels (21). The magnitude of insulin secretion in response to intestinal carbohydrate is dependent on the release of incretins, such as gastric inhibitory polypeptide (GIP) and glucagon-like pep- tide-l (GLP-1). It is not known whether these incretins affect eating behavior in humans. The aim of the present study was to investigate the effect of intestinal carbohydrate in the control of short- term satiety. Two sets of experiments were carried out; the first series compared the effects of infusions of either glucose or saline into the proximal small intes- tine while plasma glucose was maintained at the same level by intravenous infusions, and the second exam- ined the effects of small intestinal glucose when the release of gastrointestinal hormones was inhibited by octreotide (9), a long-acting analogue of somatostatin. METHODS Subjects. Subjects were seven healthy male volunteers (aged 19-35 yr) who were in the normal range for body mass index (range 20-25) (7). All volunteers scored <8 (2.7 2 1.1, mean t SE) on the restraint factor of the Eating Inventory Questionnaire (28), indicating that they were not restrained eaters. All subjects were nonsmokers, and none was taking medication. Each subject gave written informed consent, and the protocol was approved by the Human Ethics Committee of the Royal Adelaide Hospital in 1994. 0193-1849/96 $5.00 Copyright o 1996 the American Physiological Society E209