The role of postprandial releases of insulin and incretin hormones in meal-induced satiety—effect of obesity and weight reduction

BACKGROUND: Previous studies have indicated that the secretion of the intestinal satiety hormone glucagon-like peptide-1 (GLP-1) is attenuated in obese subjects.OBJECTIVE: To compare meal-induced response of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in obese and lean male subjects, to investigate the effect of a major weight reduction in the obese subjects, and to look for an association between these hormones and ad libitum food intake.METHOD: Plasma concentrations of intestinal hormones and appetite sensations were measured prior to, and every 30 min for 180 min after, ingestion of a 2.5 MJ solid test meal. Gastric emptying was estimated scintigraphically. An ad libitum lunch was served 3 h after the test meal.SUBJECTS: Nineteen non-diabetic obese (body mass index (BMI) 34.1–43.8 kg/m2) and 12 lean (BMI 20.4–24.7 kg/m2) males. All obese subjects were re-examined after a mean stabilised weight loss of 18.8 kg (95% CI 14.4–23.2).RESULTS: Total area under the GLP-1 response curve (AUCtotal, GLP-1) was lower in obese before and after the weight loss compared to lean subjects (P<0.05), although weight loss improved the response from 80 to 88% of that of the lean subjects (P=0.003). The GIP response was similar in obese and lean subjects. However, after the weight loss both AUCtotal, GIP and AUCincremental, GIP were lowered (P<0.05). An inverse correlation was observed between AUCincremental, GIP and energy intake at the subsequent ad libitum meal in all groups. In lean subjects ad libitum energy intake was largely predicted by the insulin response to the preceding meal (r 2=0.67, P=0.001).CONCLUSION: Our study confirmed previous findings of a reduced postprandial GLP-1 response in severely obese subjects. Following weight reduction, GLP-1 response in the obese subjects apparently rose to a level between that of obese and lean subjects. The data suggests that postprandial insulin and GIP responses are key players in short-term appetite regulation.

[1]  P. Groop.  The influence of body weight, age and glucose tolerance on the relationship between GIP secretion and beta-cell function in man. , 1989, Scandinavian journal of clinical and laboratory investigation.

[2]  S. Woods,et al.  Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons , 1979, Nature.

[3]  E. Ravussin,et al.  Insulin resistance associated with lower rates of weight gain in Pima Indians. , 1991, The Journal of clinical investigation.

[4]  V. Marks,et al.  Attenuated GLP-1 secretion in obesity: cause or consequence? , 1996, Gut.

[5]  D Conen,et al.  Glucagon-like peptide-1: a potent regulator of food intake in humans , 1999, Gut.

[6]  J. Holst,et al.  Differential effects of saturated and monounsaturated fatty acids on postprandial lipemia and incretin responses in healthy subjects. , 1999, The American journal of clinical nutrition.

[7]  J. Holst,et al.  Diurnal profile of pancreatic polypeptide, pancreatic glucagon, gut glucagon and insulin in human morbid obesity. , 1983, International journal of obesity.

[8]  J. Holst,et al.  Physiological augmentation of amino acid-induced insulin secretion by GIP and GLP-I but not by CCK-8. , 1995, The American journal of physiology.

[9]  S. S. St. Jeor,et al.  Augmented gastric inhibitory polypeptide and insulin responses to a meal after an increase in carbohydrate (sucrose) intake. , 1984, The Journal of clinical endocrinology and metabolism.

[10]  J. Holst,et al.  Glucagon-like peptide-1-(7-36)amide is transformed to glucagon-like peptide-1-(9-36)amide by dipeptidyl peptidase IV in the capillaries supplying the L cells of the porcine intestine. , 1999, Endocrinology.

[11]  A. Astrup,et al.  Acetylation of or beta-cyclodextrin addition to potato beneficial effect on glucose metabolism and appetite sensations. , 1997, The American journal of clinical nutrition.

[12]  T. M. Hayes,et al.  Obesity is associated with increased post-prandial GIP levels which are not reduced by dietary restriction and weight loss. , 1989, Diabete & metabolisme.

[13]  J. Holst,et al.  Glucagon-like peptide 1 undergoes differential tissue-specific metabolism in the anesthetized pig. , 1996, The American journal of physiology.

[14]  J. Holst,et al.  Degradation of glucagon-like peptide-1 by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo. , 1995, The Journal of clinical endocrinology and metabolism.

[15]  A. Astrup,et al.  Evidence for an abnormal postprandial response to a high-fat meal in women predisposed to obesity. , 1994, The American journal of physiology.

[16]  S. Rössner,et al.  Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in obese men. , 1999, International Journal of Obesity.

[17]  J. Chayvialle,et al.  Long-term influence of a wheat-bran supplemented diet on secretion of gastrointestinal hormones and on nutrient absorption in healthy man. , 1986, Human nutrition. Clinical nutrition.

[18]  M. McBurney,et al.  Dietary fiber modulates intestinal proglucagon messenger ribonucleic acid and postprandial secretion of glucagon-like peptide-1 and insulin in rats. , 1996, Endocrinology.

[19]  R. Buffenstein,et al.  Appetite dysfunction in obese males: evidence for role of hyperinsulinaemia in passive overconsumption with a high fat diet , 2000, European Journal of Clinical Nutrition.

[20]  J. Holst,et al.  Diminished immunoreactive gastric inhibitory polypeptide response to a meal in newly diagnosed type I (insulin-dependent) diabetics. , 1983, The Journal of clinical endocrinology and metabolism.

[21]  A. Andersen,et al.  Plasma enteroglucagon after jejunoileal bypass with 3:1 or 1:3 jejunoileal ratio. , 1979, Scandinavian journal of gastroenterology.

[22]  S. Hampton,et al.  The effect of dietary modification and hyperglycaemia on gastric emptying and gastric inhibitory polypeptide (GIP) secretion , 1988, British Journal of Nutrition.

[23]  A. Astrup,et al.  Resistant starch: the effect on postprandial glycemia, hormonal response, and satiety. , 1994, The American journal of clinical nutrition.

[24]  A. Astrup,et al.  Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. , 1998, The Journal of clinical investigation.

[25]  J. Holst,et al.  Glucagon-Like Peptide-1-(7-36)Amide Is Transformed to Glucagon-Like Peptide-1-(9-36)Amide by Dipeptidyl Peptidase IV in the Capillaries Supplying the L Cells of the Porcine Intestine1. , 1999, Endocrinology.

[26]  V. Marks,et al.  Inhibition of carbohydrate-mediated glucagon-like peptide-1 (7-36)amide secretion by circulating non-esterified fatty acids. , 1999, Clinical science.

[27]  P. Petocz,et al.  Interrelationships among postprandial satiety, glucose and insulin responses and changes in subsequent food intake. , 1996, European journal of clinical nutrition.

[28]  S. Toubro,et al.  Effect of obesity and major weight reduction on gastric emptying , 2000, International Journal of Obesity.

[29]  J. Holst,et al.  Rapid oscillations in plasma glucagon-like peptide-1 (GLP-1) in humans: cholinergic control of GLP-1 secretion via muscarinic receptors. , 1997, The Journal of clinical endocrinology and metabolism.

[30]  J. Holst,et al.  Tissue and Plasma Concentrations of Amidated and Glycine-Extended Glucagon-Like Peptide I in Humans , 1994, Diabetes.

[31]  D. Smith,et al.  A role for glucagon-like peptide-1 in the central regulation of feeding , 1996, Nature.

[32]  Ranganath,et al.  The effect of circulating non‐esterified fatty acids on the entero‐insular axis , 1999, European journal of clinical investigation.

[33]  M. Horowitz,et al.  Effect of intravenous glucose and euglycemic insulin infusions on short-term appetite and food intake. , 1998, The American journal of physiology.

[34]  M. Horowitz,et al.  Effect of intravenous glucose and euglycemic insulin infusions on short-term appetite and food intake. , 1998, American journal of physiology. Regulatory, integrative and comparative physiology.

[35]  A. Niijima,et al.  Vagal hepatopancreatic reflex effect evoked by intraportal appearance of tGLP-1. , 1996, The American journal of physiology.

[36]  J. Holst,et al.  Glucagon-Like Peptide I Receptors in the Subfornical Organ and the Area Postrema Are Accessible to Circulating Glucagon-Like Peptide I , 1996, Diabetes.

[37]  M. Horowitz,et al.  Gastrointestinal adaptation to diets of differing fat composition in human volunteers. , 1991, Gut.