Circadian rhythms: a regulator of gastrointestinal health and dysfunction

Introduction: Circadian rhythms regulate much of gastrointestinal physiology including cell proliferation, motility, digestion, absorption, and electrolyte balance. Disruption of circadian rhythms can have adverse consequences including the promotion of and/or exacerbation of a wide variety of gastrointestinal disorders and diseases.

Areas covered: In this review, we evaluate some of the many gastrointestinal functions that are regulated by circadian rhythms and how dysregulation of these functions may contribute to disease. This review also discusses some common gastrointestinal disorders that are known to be influenced by circadian rhythms as well as speculation about the mechanisms by which circadian rhythm disruption promotes dysfunction and disease pathogenesis. We discuss how knowledge of circadian rhythms and the advent of chrono-nutrition, chrono-pharmacology, and chrono-therapeutics might influence clinical practice.

Expert opinion: As our knowledge of circadian biology increases, it may be possible to incorporate strategies that take advantage of circadian rhythms and chronotherapy to prevent and/or treat disease.     

Effects of jejunoileal autotransplantation on gastrointestinal regulatory peptides

Plasma gastrointestinal hormones were measured before and during feeding in eight dogs, more than one year after total autotransplant of the entire jejunoileum, and in controls. At sacrifice, tissues were taken from the transplanted segment and intact bowel for measurement of hormone and enteric neuropeptide content. Gastrin levels were reduced in autotransplanted dogs (fasting 63% of control, incremental response 67% of control, bothP<0.05), reflecting the loss of acid inhibitory reflexes. Secretin and cholecystokinin responses were identical between the two groups. Postprandial levels of gastric inhibitory peptide (incremental response 175% of control,P<0.005), insulin, and peptide YY (158% of control,P<0.05) were elevated following denervation, the former suggesting more rapid gastric emptying while the latter may reflect malabsorption. The neurotensin meal response was obtunded by denervation (incremental response 43% of control,P<0.05), providing evidence for a neural pathway for its release. Pancreatic polypeptide responses were identical between the groups, suggesting intact pancreatic innervation. Abnormal hormone secretion may contribute to the impaired fed motor responses seen following extrinsic denervation of the small bowel. In contrast, the neuropeptide content of the autotransplanted small intestine is normal, suggesting that extrinsic denervation has no long-term effects on peptide content of the enteric nervous system.Presented in part at the Sixth Biennial Symposium of the American Motility Society, Newport, Rhode Island, October 15, 1990; and has appeared in part in abstract form: Gastroenterology 96:1228, 1990, and Gastroenterology 100:A413, 1991.     

The role of gastrin and cholecystokinin in normal and neoplastic gastrointestinal growth

Abstract Gastrin and cholecystokinin (CCK) act as growth factors for the gastric mucosa and the pancreas, respectively. CCK is also responsible, via the CCK-A receptor, for the pancreatic hyperplasia observed following the feeding of protease inhibitors or pancreaticobiliary diversion. Hypergastrinaemia does not increase the incidence of spontaneous gastrointestinal carcinoma, but does stimulate the proliferation of gastric enterochromaffin-like cells via the gastrin/CCK-B receptor, with a consequent increase in the incidence of gastric carcinoids. Whether gastrin influences mutagen-induced gastrointestinal carcinogenesis is still controversial, but CCK clearly enhances the induction by carcinogens of acinar tumours in the pancreas. While gastrin increases xenograft growth of 50% of gastrointestinal tumours tested, effects on the proliferation of gastrointestinal tumour cell lines in vitro have been more difficult to demonstrate, perhaps because many cell lines are already maximally stimulated by autocrine gastrin. Gastrin mRNA and progastrin, but not mature amidated gastrin, have been detected in all gastrointestinal cell lines tested. Although cell proliferation is inhibited by gastrin/CCK receptor antagonists, the spectrum of antagonist affinities is not consistent with binding to either CCK-A or gastrin/CCK-B receptors. Definition of the molecular structure of the receptor involved in the autocrine loop may lead to novel therapies for gastrointestinal cancer.     

The role of gastrointestinal peptides on pancreatic secretion in response to different stimulants in conscious rats

Summary Effects of intragastric food, intraduodenal amino acids, and intravenously administered bombesin and gastrin-releasing peptide (GRP) were examined in conscious rats with pancreatic fistula in terms of responses of exocrine pancreatic secretion, plasma levels gastrin, and cholecystokinin (CCK). Pancreatic juice and blood samples were collected at regular intervals before and after the stimuli. Intragastric food increased pancreatic secretion and plasma levels of gastrin and CCK. Intraduodenal infusion of amino acids had no effect on pancreatic secretion and plasma levels of gastrin and CCK. Intravenous infusion of bombesin at 1 μg/kg/h induced significant increases in pancreatic volume and protein outputs, but had no effect on plasma levels of gastrin and CCK. Bombesin infusion at 10 μg/kg/h resulted in significant increases in pancreatic volume and protein outputs as well as plasma gastrin levels, but had no effect on plasma CCK levels. Intravenous infusion of GRP induced increases in pancreatic volume and protein outputs and plasma gastrin levels, but had no effect on CCK levels. Antrectomy resulted in significant decreases in basal levels of plasma gastrin. GRP-stimulated pancreatic volume and protein outputs were not significantly changed by antrectomy. In rats that underwent antrectomy, GRP infusion significantly increased pancreatic volume and protein outputs, but had no effect on plasma levels of gastrin and CCK. Food-stimulated pancreatic secretion and plasma levels of gastrointestinal peptides of rats were similar to other species, but amino acids, bombesin, or GRP may not be the stimulants for CCK release in rats. The stimuli that release CCK from duodenal mucosa probably varies among species.     

高血压病心血管重构与血压昼夜节律性

目的 :研究血压昼夜节律性变化对高血压病患者心脏和大动脉重构的影响。方法 :对 64例 1～ 2级高血压病患者进行 2 4h动态血压监测 ,并以超声检测心脏结构指标及主动脉、股动脉、月国动脉管腔内径、内膜中层厚度等动脉结构指标及反映动脉顺应性或扩张性的功能指标。以协方差分析校正可能的混杂因素影响后 ,对比动态血压昼夜节律呈杓型和非杓型的高血压病患者心血管重构指标的差异 ,并以 3 6例正常血压者作对照。结果 :血压昼夜节律异常的非杓型组高血压病患者与正常血压对照组相比 ,左房内径、左室壁厚度、左室肌重量明显增加 ,主动脉、股动脉及月国动脉内膜中层厚度及面积增大 ,内膜中层厚度 /腔径比值及内膜中层面积 /管腔面积比值显著增高 ;主动脉还有管腔内径及面积增大 ,脉搏波速度明显增快 ,差异有统计学显著性 ,经协方差分析校正年龄、性别、体重指数、心率、吸烟情况、血糖血脂水平等可能对心血管重构的影响后 ,显著性仍然存在 ,仅股动脉重构性指标统计学显著性降低。而昼夜节律正常的杓型高血压组与正常血压对照组相比 ,心脏和血管重构性变化指标多无显著性差异 ,结论 :轻中度高血压病时 ,血压昼夜节律异常可能对心脏和大动脉重构有不利影响     

原发性高血压患者动态血压节律异常对利钠肽及左室质量的影响

目的:评价原发性高血压(EH)患者动态血压节律异常对利钠肽及左室质量的影响.方法:根据24 h动态血压结果将65例EH患者分为杓形高血压组与非杓形高血压组,分别进行了血心房利钠肽(ANP)、脑钠肽(BNP)及超声心动图测定.结果:杓形高血压组与非杓形高血压组的ANP、BNP及左室质量指数(LVMI)均显著高于对照组(P<0 01);其中非杓形高血压组显著高于杓形高血压组(P<0 01);且ANP、BNP浓度与LVMI呈正相关(R=0 45,0 67;P< 0 01).结论:EH患者血压昼夜节律异常者,心脏ANP分泌增加,与LVMI呈正相关性.     

Delayed circadian rhythms in older Africans living with human immunodeficiency virus (HIV)

The increasing number of people living with human immunodeficiency virus, HIV, (PLWH) have an elevated incidence of risk for noncommunicable comorbidities, the aetiology of which remains incompletely understood. While sleep disturbances are often reported in PLWH, it is unknown to what extent they relate to changes in the circadian and/or sleep homeostatic processes. We studied the relationship between sleep characteristics, circadian phase, and HIV status in older adults from the HAALSI (Health and Ageing in Africa: a Longitudinal Study of an INDEPTH Community in South Africa) subsample of the Agincourt Health and Demographic Surveillance System in South Africa (n = 187, 36 human immunodeficiency virus positive [HIV+], age: 66.7 ± 11.5 years, range 45—93 years), where HIV prevalence is high and (in contrast to the global north) does not associate significantly with potentially confounding behavioural differences. In participants with valid actigraphy data (n = 172), regression analyses adjusted for age and sex indicated that HIV+ participants had slightly later sleep onset (β = .16, p = .039), earlier sleep offset times (β = −.16, p = .049) and shorter total sleep times (β = −.20, p = .009) compared to the HIV negative (HIV−) participants. In a subset of participants (n = 51, 11 HIV+), we observed a later dim light melatonin onset (DLMO) in HIV+ (21:16 ± 01:47) than in HIV− (20:06 ± 00:58) participants (p = .006). This substantial difference remained when adjusted for age and sex (β = 1.21; p = .006). In 36 participants (6 HIV+) with DLMO and actigraphy data, median phase angle of entrainment was −6 min in the HIV+ group and +1 h 25 min in the HIV− group. DLMO time correlated with sleep offset (ρ = 0.47, p = .005) but not sleep onset (ρ = −0.086, p = .623). Collectively, our data suggest that the sleep phase occurred earlier than what would be biologically optimal among the HIV+ participants. This is the first report of a mistimed circadian phase in PLWH, which has important potential implications for their health and well-being, especially given the well-established relationships between circadian asynchrony and sleep deprivation with poorer health outcomes.     

Circadian rhythms in the number of gastrin cells,DNA synthesizing cells and labelling index of gastrin cells in the antral mucosa of the rat

Circadian variations of the gastrin cell (G-cell) number, the DNA synthesizing cell (S phase cell) number and labelling index of G-cell in antral mucosa were studied using the simultaneous double immunoenzymatic labelling method of gastrin and bromodeoxyuridine (BrdU) both in fed and 24 h fasted rats. No significant change was observed in the G-cell number. The S phase cell number and labelling index of G-cell showed significant circadian rhythms. Labelling index of G-cell markedly decreased in 24 h fasted rats in comparison to that in fed rats. These results suggest that DNA synthesis in G-cells has a circadian rhythm and that the activity is influenced by food ingestion.     

昼夜节律变化对动脉粥样硬化形成的影响及其相关通路的研究进展

地球上几乎所有的生命都存在昼夜节律,控制昼夜节律的生物钟具有重要的生理功能,同时也是疾病的重要调节器.昼夜节律与动脉粥样硬化关系密切.研究表明受损的生物钟会影响造血过程和糖脂代谢,并改变局部斑块病变中的细胞功能.在分子水平上,昼夜节律可以通过Toll样受体(TLR)通路调节动脉粥样硬化炎症状态和血管重塑,通过蛋白激酶B...     

Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock

In mammals, multiple physiological, metabolic, and behavioral processes are subject to circadian rhythms, adapting to changing light in the environment. Here we analyzed circadian rhythms in the fecal microbiota of mice using deep sequencing, and found that the absolute amount of fecal bacteria and the abundance of Bacteroidetes exhibited circadian rhythmicity, which was more pronounced in female mice. Disruption of the host circadian clock by deletion of Bmal1, a gene encoding a core molecular clock component, abolished rhythmicity in the fecal microbiota composition in both genders. Bmal1 deletion also induced alterations in bacterial abundances in feces, with differential effects based on sex. Thus, although host behavior, such as time of feeding, is of recognized importance, here we show that sex interacts with the host circadian clock, and they collectively shape the circadian rhythmicity and composition of the fecal microbiota in mice.The composition of intestinal microbiota is influenced by host genetics (1), aging (2), antibiotic exposure (3), lifestyle (4), diet (5), pet ownership (6), and concomitant disease (7, 8). The impact of diet in shaping the composition of the microbiota has been well established in both humans and mice (9, 10). The type of food consumed and also the feeding behavior of the host influence the microbiota. For example, a 24-h fast increases the abundance of Bacteroidetes and reduces that of Firmicutes in mouse cecum, without altering the communal microbial diversity (11). Bacteroidetes are also dominant in the microbiota of the fasted Burmese python, whereas ingestion of a meal shifts the intestinal composition toward Firmicutes (12).The rotation of the earth results in the oscillation of light during the 24-h cycle. Organisms adapted to this cycle by developing a circadian rhythm, an endogenous and entrainable mechanism that times daily events such as feeding, temperature, sleep-wakefulness, hormone secretion, and metabolic homeostasis (13, 14). In mammals, this rhythm is controlled by a master clock that resides in the suprachiasmatic nucleus of the hypothalamus. It responds to the changing light cycle and signals this information to peripheral clocks in most tissues (15). The core mammalian clock is comprised of activators BMAL1 and CLOCK as well as repressors PERIOD (PER) and CRYPTOCHROME (CRY), forming an interlocked regulatory loop (14).Circadian rhythms also exist in fungi and cyanobacteria (16). For example, a pacemaker in cyanobacteria transduces the oscillating daylight signal to regulate gene expression and to time cell division (17, 18). Hence, the synchronization of endogenous circadian rhythms with the environment is crucial for the survival of the bacteria as well as metazoa.Recent studies show that the intestinal microbiota undergo diurnal oscillation under the control of host feeding time, and that ablation of the host molecular clock Per genes causes dysbiosis (19, 20). Here, we report that microbial composition and its oscillation are influenced by the host clock, including the Bmal1-dependent forward limb of the signaling pathway. We also find that rhythmicity is conditioned by the sex of the host, being more pronounced in females than in males.     

Effects of a one-hour light pulse on the timing of the circadian rhythm in melatonin secretion in rams

Abstract: The effects of a 1-hr light pulse on the timing of the circadian rhythm in the blood plasma concentration of melatonin were documented in Soay rams. Groups of 5 to 6 animals were transferred from short days (LD 8: 16) to constant dim red light (DD) for 6 days, and were exposed to a 1-hr light pulse at one of 16 different times throughout 24 hr on day 3. Blood samples were collected hourly for 30 hr before (day 2–3) and after the light pulse (day 5–6), and the plasma concentrations of melatonin were measured by radioimmunoassay. The animals were allocated to experimental groups based on the circadian time (CT) when the light pulse was given using two hourly blocks through the circadian day; the onset of enhanced melatonin secretion (melatonin peak) was designated as CT 12. Under DD there was a clearly defined plasma melatonin rhythm in all animals. The mean duration of the melatonin peak was 13.24 ± 0.16 hr (n = 91) and the mean period between the onset of successive melatonin peaks was 23.55 ± 0.10 hr (n = 21). The effect of the 1-hr light pulse on the time of onset of the melatonin peak varied significantly with the circadian time when the light pulse was given (ANOVA, P= 0.031). Light-induced significant (pre- vs post-pulse onset, Students t-test, P < 0.05) phase delays in the onset of the melatonin peak in the early subjective day at CT 2.5 hrs (mean ø: -1.9 hr), and in the early subjective night at CT 12.5 and 14.5 (mean ø: -2.0 hrs), but not at other times. The light pulse never induced significant phase advances. The effects of the light pulse on the offset of plasma melatonin peak did not vary significantly with the time of the light pulse (ANOVA, P= 0.780), although significant differences in the pre- and post-pulse offset occurred at CT 14.5 and 18.5 (mean ø: -1.5 hr). The differential changes in the onset and the offset of the melatonin peak resulted in changes in the duration of the peak (maximum difference between means: 3.8 hr). The results indicate that entrainment occurs under natural 24 hr LD cycles when light impinges on the early subjective night and induces a net phase delay, thus extending the period of the melatonin rhythm to 24 hr. This causes a close phase relationship between the end of the light period and the onset of the melatonin peak as occurs in sheep under natural cycles. The results are also consistent with a multiple oscillator governing melatonin secretion, and that differential entrainment of the component oscillators by light affects the duration of the melatonin peak.     

Roles of gastrointestinal hormones in pancreatic cancer

Several gastrointestinal (GI) hormones, such as gastrin, cholecystokinin, and bombesin, have been reported to affect the development of pancreatic cancer. The receptors for these hormones are found in normal and neoplastic pancreatic cells. Activation of these receptors enhances pancreatic carcinogenesis and promotes the growth of established pancreatic carcinoma either in vitro or in vivo. On the other hand, some studies have shown that these GI hormones may have no effect or may play an inhibitory role in the development of pancreatic cancer. The reasons for the apparent discrepancies in the published literature are discussed in this review. In recent years, increasing emphasis has been placed on the effects of GI hormones on cancer invasion and metastasis. As the transition from noninvasion to the invasive state is the crucial event in cancer development, further investigation of the way in which GI hormones affect the invasion and metastasis of pancreatic cancer may be important for the development of new therapeutic approaches with eventual clinical utility.     

Phase-shifting effects of light on the circadian rhythms of 5-methoxytryptophol and melatonin in the chick pineal gland

In the chick pineal gland, 5-methoxytryptophol and melatonin concentrations fluctuate in a rhythmic manner. These rhythms are circadian in nature persisting in constant darkness and have opposite phases. Acute exposure of chicks to white light (30 lux for 5, 10, 20, and 30 min) at night increased the amount of pineal 5-methoxytryptophol and decreased pineal melatonin content. A 6 hr pulse of light (100 lux) applied early in the subjective night (CT12-CT18) caused a delay in the phase of the circadian rhythms of 5-methoxytryptophol and melatonin by 3.7 and 4.5 h, respectively, compared to untreated controls. When the 6 hr light pulse was given during the late subjective night (C18 CT24) it advanced the phase of the 5-methoxytryptophol and melatonin rhythms by 8.1 and 11.9 h, respectively. In the chick pineal the phase-advancing effects of light on the circadian rhythms of 5-methoxytryptophol and melatonin were more pronounced than the phase-delaying effects. Our results provide the first evidence that light is capable of phase shifting the 5-methoxytryptophol rhythm in a manner similar to its action on the melatonin rhythm.     

昼夜节律在病毒感染中的作用

昼夜节律是由内源性时钟调节的多个生物过程的日常振荡,调控机体的各种生理变化.节律紊乱会导致多种疾病的发生,包括代谢综合征和癌症等.最近将昼夜节律系统作用研究扩展到了感染的调控,宿主与病原体的相互作用以及由此产生的疾病结局.深入了解昼夜节律系统在调节病毒感染中的作用将为病毒性传染病的致病机理、抗病毒治疗、疫苗研发等提供新的思路.本文就昼夜节律与病毒感染的相互作用进行综述,包括昼夜节律如何影响病毒感染以及病毒如何调节节律以促进自身复制的关键发现,突出昼夜节律的重要性.     

Effect of long-term dietary protein intake on glucose metabolism in humans

Aims/hypothesis. A meal rich in protein stimulates insulin secretion. Long-term effects of dietary protein on insulin release and glucose metabolism are, however, still not known. Our study focussed on the effect of different protein intake on pancreatic insulin secretion capacity, glycogen turnover and gluconeogenesis.¶Methods. Subjects with constant (6 months) dietary protein of 1.87 ± 0.26 g · kg^–1· day^–1 (1.25–2.41) named high protein group and with 0.74 ± 0.08 (0.57–0.80), normal protein group, were identified by a food questionnaire and were matched (n = 9) according to sex, age and calorie intake. They underwent an intravenous glucose tolerance test and a euglycaemic hyperinsulinaemic clamp with infusion of [6,6-²H₂]-glucose combined with indirect calorimetry. To estimate net gluconeogenesis the usual diet was enriched by deuterated water or U-[¹³C₆]-glucose and breath and plasma were sampled.¶Results. Glucose-stimulated insulin secretion was increased in the high protein group (516 ± 45 pmol/l vs 305 ± 32, p = 0.012) due to reduced glucose threshold of the endocrine beta cells (4.2 ± 0.5 mmol/l vs 4.9 ± 0.3, p = 0.031). Endogeneous glucose output was increased by 12 % (p = 0.009) at 40 pmol/l plasma insulin in the high protein group, but not at higher insulin concentration whereas overall glucose disposal was reduced. Fasting plasma glucagon was 34 % increased in the high protein group (p = 0.038). Fractional gluconeogenesis was increased by 40 % in subjects receiving a high protein diet as determined by both methods.¶Conclusion/interpretation. High protein diet is accompanied by increased stimulation of glucagon and insulin within the endocrine pancreas, high glycogen turnover and stimulation of gluconeogenesis. [Diabetologia (2000) 43: 1257–1265]     

比索洛尔对高血压左室肥厚与血压昼夜节律异常的影响

目的 :观察高血压左室肥厚 (LVH)与血压昼夜节律关系及比索洛尔对其影响。方法 :4 5例原发性高血压 (EH)伴LVH患者服药前行动态血压及超声心动图检测 ,并于服药后 8周进行复查比较。结果 :血压昼夜节律消失组 30例 ,血压昼夜节律正常组 15例。血压昼夜节律消失组 2 4h收缩压、夜间血压、血压负荷均高于血压昼夜节律正常组。昼夜节律消失组服用比索洛尔 8周后 ,昼夜节律、室间隔厚度、左室后壁厚度、左室重量指数、舒张晚期血流峰速、等容舒张时间均有明显改善 ,血压昼夜节律正常组左室功能也有改善。结论 :高血压LVH患者血压昼夜节律消失多见 ,索他洛尔可使血压昼夜节律趋于正常 ,可使左室功能改善     

珍菊降压片联合氨氯地平片对大鼠收缩压内皮素及一氧化氮昼夜节律的影响

目的观察和比较联服珍菊降压片、氨氯地平片与单服氨氯地平片治疗前、后大鼠血内皮素1(ET-1)、一氧化氮(NO)和收缩压的昼夜节律变化。方法实验大鼠分2组,随机分为灌服苯磺酸氨氯地平片组(2.5 mg.kg-1.d-1)(组Ⅰ)、灌服苯磺酸氨氯地平片(2.5 mg.kg-1.d-1)和珍菊降压片组(40 mg.kg-1.d-1)(组Ⅱ),每大组各32只,每大组又分4小组,每小组各8只。疗程4周,分别在灌药前、后应用鼠尾测压仪测量大鼠收缩压和测量血ET-1及NO水平。结果两组服药4周后与服药前比较,收缩压及血浆ET-1水平均降低、血清NO均升高,以组Ⅱ变化显著。两组大鼠经服药后收缩压、血ET-1和NO曲线峰值相位均发生了不同程度移位。治疗后两组峰值相位比较,组Ⅰ的收缩压峰值相位为-47°(20∶51)比组Ⅱ33°(21∶47)(P=0.04),ET-1组Ⅰ为200°(13∶10)比组Ⅱ95°(06∶12)(P<0.001),NO组Ⅰ55°(04∶00)比组Ⅱ65°(03∶20)(P=0.04)。珍菊降压片和氨氯地平片对大鼠收缩压、血ET-1和NO的昼夜节律有显著影响。结论珍菊降压片、氨氯地平片联用在改善血管内皮功能方面具有协同作用,可更好地控制血压,同时可以维持血压昼夜节律,保护靶器官,减少心脑血管并发症的发生率。     

Specific adaptation of gastric emptying to diets with differing protein content in the rat: is endogenous cholecystokinin implicated?

Background—Recent studies indicate that gastricemptying may be influenced by patterns of previous nutrient intake.Endogenous cholecystokinin (CCK), whose synthesis and release can beaffected by dietary intake, has a major role in the regulation ofgastric emptying.
Aims—To evaluate the influence of diets withdiffering protein content on gastric emptying of differing liquid testmeals and plasma CCK levels in the rat and to check whether theinhibitory effect of exogenous CCK on gastric emptying is modifiedafter long term intake of diets with differing protein content.
Methods—Rats were fed for three weeks with highprotein, medium protein (regular), or low protein diet. On day 22 gastric emptying of a peptone meal was studied. In addition, basal and postprandial CCK levels after the different dietary regimens were measured by bioassay. The time course of dietary adaptation was studiedand its specificity assessed through the use of different (peptone,glucose, and methylcellulose) test meals. The effect of exogenous CCK-8on gastric emptying was studied at the end of the adaptation period(three weeks).
Results—Feeding the animals with a high proteindiet for three weeks resulted in a significant (p<0.05) acceleration(by 21.2(8.2)%) of gastric emptying while feeding with a low proteindiet was followed by a significant (p<0.05) delay (by 24.0 (6.2)%) inthe emptying rate. When the time course of the effect of dietary adaptation on gastric emptying was studied, it appeared that at leasttwo weeks are required for dietary protein to be effective. Theregulatory effect of dietary protein on gastric emptying proved to bedependent on meal composition. Only the emptying rate of a proteincontaining meal (40% peptone) was significantly modified by previousdietary intake. No significant (p>0.05) changes were observed withglucose and methylcellulose meals whose emptying rates were similar inrats receiving a high protein or low protein diet. A peptone mealstrongly and significantly (p<0.05) increased plasma CCK levels inrats fed a medium protein (regular) diet. Results were similar in ratsreceiving a low protein diet (p<0.05) but not in rats on a highprotein diet (p>0.05). As a consequence, postprandial plasma levels ofCCK in rats fed with a medium or low protein diet were significantly(p<0.05) higher than those in rats receiving a high protein diet. Inrats on high and low protein diets, dose response curves to CCK-8 werevirtually identical, suggesting that dietary protein intake has noinfluence on the effect of exogenous CCK.
Conclusions—These results clearly show thatgastric emptying of a protein containing meal can be modified byprevious dietary protein intake. This effect, which is time dependentand meal specific, may be related to changes in endogenous CCK release which will affect emptying rate. While the exact mechanisms underlying this adaptive response need to be studied and clarified further, theseresults emphasise the importance of dietary history in the evaluationand interpretation of gastric emptying data.

Keywords:diet; protein content; gastric emptying; cholecystokinin