The effect of feeding frequency on insulin and ghrelin responses in human subjects

Abstract

Recent work shows that increased meal frequency reduces ghrelin responses in sheep. Human research suggests there is an interaction between insulin and ghrelin. The effect of meal frequency on this interaction is unknown. Therefore, we investigated the effect of feeding frequency on insulin and ghrelin responses in human subjects. Five healthy male volunteers were recruited from the general population: age 24 (SEM 2) years, body mass 75·7 (SEM 3·2) kg and BMI 23·8 (SEM 0·8) kg/m 2 . Volunteers underwent three 8-h feeding regimens: fasting (FAST); low-frequency (two) meal ingestion (LOFREQ MEAL ); high-frequency (twelve) meal ingestion (HIFREQ MEAL ). Meals were equi-energetic within trials, consisting of 64 % carbohydrate, 23 % fat and 13 % protein. Total energy intake was equal between feeding trials. Total area under the curve for serum insulin and plasma ghrelin responses did not differ between trials (P.0·05), although the hormonal response patterns to the two meal feeding regimens were different. An inverse relationship was found between serum insulin and plasma ghrelin during the FAST and LOFREQ MEAL trials (P,0·05); and, in the postprandial period, there was a time delay between insulin responses and successive ghrelin responses. This relationship was not observed during the HIFREQ MEAL trial (P.0·05). This study provides further evidence that the postprandial fall in ghrelin might be due, at least partially, to the rise in insulin and that high-frequency feeding may disrupt this relationship. Ghrelin: Insulin: Feeding frequency: Snacking: AppetiteThe recent escalating obesity trend in man is due to an imbalance between energy intake and energy expenditure (1,2) . Energy intake is influenced by the effect of food's energy density, total energy content and feeding frequency and the extent to which these alter satiety. Of these factors, feeding frequency has received least attention. Epidemiological evidence in human subjects indicates increasing trends in recent years of dietary snacking and increased meal frequency (3,4) and such studies show positive relationships between snacking and increased energy intake and BMI (4) , illustrating the potential importance of investigating feeding frequency.Several gastrointestinal peptides are involved in metabolic processes and are dysregulated in states of metabolic disease (5 -7) . One of these peptides, ghrelin, an orexigenic hormone released by the stomach prior to feeding, has also been implicated in the control of fuel metabolism, appetite and pancreatic insulin release, factors quite central to the onset of metabolic disease (8)

Changes in gut hormone and glucose concentrations in relation to hunger and fullness

“…Frecka and Mattes (34) showed that peak insulin concentrations preceded nadir ghrelin concentrations. Moreover, Solomon et al (28) reported that there is a delay of ;20 min between responses of insulin and ghrelin, insulin leading ghrelin. Our study confirmed the findings by Solomon et al (28): changes in ghrelin concentrations lagged behind the changes in insulin concentrations by ;15-30 min in the staggered meal condition and by ;30 min in the nonstaggered meal condition.…”

“…Moreover, Solomon et al (28) reported that there is a delay of ;20 min between responses of insulin and ghrelin, insulin leading ghrelin. Our study confirmed the findings by Solomon et al (28): changes in ghrelin concentrations lagged behind the changes in insulin concentrations by ;15-30 min in the staggered meal condition and by ;30 min in the nonstaggered meal condition. This may suggest a role for insulin as a possible negative regulator of ghrelin (38).…”

“…Several studies showed that insulin is required for postprandial ghrelin suppression (30)(31)(32). Moreover, Solomon et al (28) documented that there is a delay (;20 min) between responses of insulin and ghrelin, insulin leading ghrelin. Therefore, we analyzed the strength of the within-subject relation between ghrelin and insulin concentrations using the same statistics as those used for the analyses of the strength of the within-subject relation between VAS appetite scores and hormone and glucose concentrations.…”

Hyperglycemia abolishes meal-induced satiety by a dysregulation of ghrelin and peptide YY3–36 in healthy overweight/obese humans

“…The role of insulin in ghrelin regulation remains controversial; however, with the stimulatory effect of glucose on insulin secretion, this hormone may also play a role in the consequence of hyperglycemia on ghrelin levels. Although several studies have shown that supraphysiological doses of insulin suppress ghrelin levels (11,21,26,37), others have found that when provided in physiological doses, insulin has no effect of on ghrelin (7,33). Herein, we found that during the hyperglycemia trial, despite progressively larger and exaggerated insulinemic responses to each meal, the postprandial suppression of ghrelin was absent.…”

Energy Thermodynamics Revisited: Energy intake strategies for optimizing athlete body composition and performance

“…Anderwalt et al (2003) found that ghrelin was unchanged in type 2 diabetics following insulin treatment, but a rise in serum insulin that occurs following a meal had the effect of suppressing ghrelin and reducing appetite in non-diabetics. Assessing a small group (n = 5) of young adult males, Solomon, Chambers, Jeukendrup, Toogood, and Blannin (2008) also found that the postprandial fall in ghrelin is likely due to the rise in insulin, but that this relationship does not exist with the hyperinsulinemia associated with insulin resistance. Isacco et al (2010) studied a group of 278 healthy French schoolchildren, between 6 and 8 years old and found that skipping breakfast and consuming sugar-sweetened beverages while watching TV are both likely factors in unsuppressed ghrelin, hyperinsulinemia, or both, and that these behaviors were associated with significantly higher BMI, sum of 4 skinfolds, and waist circumference.…”