A novel method of sacral nerve stimulation for colonic inflammation.

BACKGROUND: Vagal nerve stimulation has been reported to treat inflammation with promising results. The aims of our study were to optimize sacral nerve stimulation (SNS) methodologies for colonic inflammation in a rodent model of colitis and to investigate autonomic and cytokine mechanisms. METHODS: Three major efforts were made in optimizing SNS: (a) to determine the best stimulation duration: SNS-0.5h daily, SNS-1h daily, and SNS-3h daily with the parameters set at 5 Hz, 10 seconds on, 90 seconds off; (b) to determine the best stimulation position: bilateral, bipolar, and unipolar stimulation; (c) to determine the best stimulation parameters: our 5 Hz intermittent stimulation vs 14 Hz-210 µs continuous stimulation. Inflammatory responses were assessed by the disease activity index (DAI), histological analyses, and the myeloperoxidase (MPO) activity. Levels of inflammatory cytokines, norepinephrine (NE), and pancreatic polypeptide (PP) in both plasma and colon tissues were assessed. KEY RESULTS: Both SNS-1h and SNS-3h significantly ameliorated intestinal inflammation; SNS-1h was superior to SNS-3h. Bipolar but not bilateral or unipolar stimulation improved the inflammation in colitis. SNS with 5 Hz intermittent stimulation but not the 14 Hz continuous SNS was better for treating colitis in rats. SNS with the optimized stimulation parameters increased vagal activity and decreased sympathetic activity. CONCLUSION & INFERENCES: Bipolar stimulation for 1 hour daily using intermittent 5 Hz parameters is most effective in improving colonic inflammation in TNBS-treated rats by inhibiting pro-inflammatory cytokines and increasing anti-inflammatory cytokines via the modulation of the autonomic function.

Sacral nerve stimulation with appropriate parameters improves constipation in rats by enhancing colon motility mediated via the autonomic-cholinergic mechanisms.

Although sacral nerve stimulation (SNS) has been applied for treating constipation, its parameters were adopted from SNS for fecal incontinence, its effects are limited, and mechanisms are largely unknown. We investigated the effects and mechanism of SNS with appropriate parameters on constipation in rats treated with loperamide. First, using rectal compliance as an outcome measure, an experiment was performed to derive effective SNS parameters. Then, a 7-day SNS was performed in rats with constipation induced by loperamide. Autonomic functions were assessed by spectral analysis of heart rate variability (HRV) derived from an electrocardiogram. Serum levels of pancreatic polypeptide (PP), norepinephrine (NE), and acetylcholine (ACh) in colon were assessed. 1) Acute SNS at 5 Hz, 100 µs was found effective in enhancing rectal compliance and accelerating distal colon transit (P < 0.05 vs. sham SNS). 2) The 7-day SNS normalized loperamide-induced constipation, assessed by the number, weight, and water content of fecal pellets, and accelerated the distal colon transit (29.4 ± 3.7 min with sham SNS vs. 16.4 ± 5.3 min with SNS but not gastric emptying or intestinal transit. 3) SNS significantly increased vagal activity (P = 0.035) and decreased sympathetic activity (P = 0.012), assessed by spectral analysis of HRV as well as by the serum PP. 4) SNS increased ACh in the colon tissue; atropine blocked the accelerative effect of SNS on distal colon transit. We concluded that SNS with appropriate parameters improves constipation induced by loperamide by accelerating distal colon motility, mediated via the autonomic-cholinergic function.NEW & NOTEWORTHY Although sacral nerve stimulation (SNS) has been applied for treating constipation, its parameters were adopted from SNS for fecal incontinence, effects are limited, and mechanisms are largely unknown. This paper shows that SNS with appropriate parameters improves constipation induced by loperamide by accelerating distal colon motility mediated via the autonomic-cholinergic function.

Novel essential amino acid supplements enriched with L-leucine facilitate increased protein and energy intakes in older women: a randomised controlled trial.

BACKGROUND: Inadequate protein intake (PI), containing a sub-optimal source of essential amino acids (EAAs), and reduced appetite are contributing factors to age-related sarcopenia. The satiating effects of dietary protein per se may negatively affect energy intake (EI), thus there is a need to explore alternative strategies to facilitate PI without compromising appetite and subsequent EI. METHODS: Older women completed two experiments (EXP1 and EXP2) where they consumed either a Bar (565 kJ), a Gel (477 kJ), both rich in EAAs (7.5 g, 40% L-leucine), or nothing (Control). In EXP1, participants (n = 10, 68 ± 5 years, mean ± SD) consumed Bar, Gel or Control with appetite sensations and appetite-related hormonal responses monitored for one hour, followed by consumption of an ad libitum breakfast (ALB). In EXP2, participants (n = 11, 69 ± 5 years) ingested Bar, Gel or Control alongside an ALB. RESULTS: In EXP1, EI at ALB was not different (P = 0.674) between conditions (1179 ± 566, 1254 ± 511, 1206 ± 550 kJ for the Control, Bar, and Gel respectively). However, total EI was significantly higher in the Bar and Gel compared to the Control after accounting for the energy content of the supplements (P < 0.0005). Analysis revealed significantly higher appetite Area under the Curve (AUC) (P < 0.007), a tendency for higher acylated ghrelin AUC (P = 0.087), and significantly lower pancreatic polypeptide AUC (P = 0.02) in the Control compared with the Bar and Gel. In EXP2, EI at ALB was significantly higher (P = 0.028) in the Control (1282 ± 513 kJ) compared to the Bar (1026 ± 565 kJ) and Gel (1064 ± 495 kJ). However, total EI was significantly higher in the Bar and Gel after accounting for the energy content of the supplements (P < 0.007). CONCLUSIONS: Supplementation with either the Bar or Gel increased total energy intake whether consumed one hour before or during breakfast. This may represent an effective nutritional means for addressing protein and total energy deficiencies in older women. TRIAL REGISTRATION: Clinical trial register: retrospectively registered, ISRCTN12977929 on.

Gut microbiota fermentation of prebiotics increases satietogenic and incretin gut peptide production with consequences for appetite sensation and glucose response after a meal.

BACKGROUND: We have previously shown that gut microbial fermentation of prebiotics promotes satiety and lowers hunger and energy intake in humans. In rodents, these effects are associated with an increase in plasma gut peptide concentrations, which are involved in appetite regulation and glucose homeostasis. OBJECTIVE: Our aim was to examine the effects of prebiotic supplementation on satiety and related hormones during a test meal for human volunteers by using a noninvasive micromethod for blood sampling to measure plasma gut peptide concentrations. DESIGN: This study was a randomized, double-blind, parallel, placebo-controlled trial. A total of 10 healthy adults (5 men and 5 women) were randomly assigned to groups that received either 16 g prebiotics/d or 16 g dextrin maltose/d for 2 wk. Meal tolerance tests were performed in the morning to measure the following: hydrogen breath test, satiety, glucose homeostasis, and related hormone response. RESULTS: We show that the prebiotic treatment increased breath-hydrogen excretion (a marker of gut microbiota fermentation) by approximately 3-fold and lowered hunger rates. Prebiotics increased plasma glucagon-like peptide 1 and peptide YY concentrations, whereas postprandial plasma glucose responses decreased after the standardized meal. The areas under the curve for plasma glucagon-like peptide 1 and breath-hydrogen excretion measured after the meal (0-60 min) were significantly correlated (r = 0.85, P = 0.007). The glucose response was inversely correlated with the breath-hydrogen excretion areas under the curve (0-180 min; r = -0.73, P = 0.02). CONCLUSION: Prebiotic supplementation was associated with an increase in plasma gut peptide concentrations (glucagon-like peptide 1 and peptide YY), which may contribute in part to changes in appetite sensation and glucose excursion responses after a meal in healthy subjects.

Hypokalemic rhabdomyolysis without watery diarrhea: an unexpected presentation of a pancreatic neuro-endocrine tumor.

Pancreatic polypeptide (PP) islet cell tumors are usually not associated with a distinct clinical syndrome, although some reports suggest that they can cause a watery diarrhea syndrome similar to vasoactive intestinal polypeptide (VIP) cell tumors. We report the case of a young woman with an unusual presentation of a pancreatic neuroendocrine tumor mainly secreting PP. The patient developed a reversible hypokalemic rhabdomyolysis very likely secondary to the presence of the tumor. The myopathy resolved following the restoration of normokaliemia using potassium supplementation and a partial laparoscopic pancreasectomy. Isolated cases of hypokalemic rhabdomyolysis induced by intestinal diseases have been described in literature but these did not include gastroenteropancreatic neoplasms. We suggest that pancreatic neuroendocrine tumors should be added to the list of intestinal diseases capable of producing hypokalemic myopathy.

Gastric electrical stimulation is associated with improvement in pancreatic exocrine function in humans.

OBJECTIVE: To define the possible effects of gastric electrical stimulation (GES) for gastroparesis on pancreatic function, we performed 2 related human studies. METHODS: Fecal elastase values were compared in 2 patient groups: (1) GES devices ON and (2) GES devices OFF and (2) in 3 control groups: (1) no response (NR) to prokinetic medications, (2) positive response (RES) to medications, and (3) normal controls. Polypeptide levels in 7 of 9 GES patients with device ON and OFF, elastase results, GI symptoms (TSS), and heart rate variability (HRV) were compared by paired t tests and/or ANOVA and reported as mean +/- SE. RESULTS: Elastase was different for GES-ON and OFF (508.0 +/- 92.2 vs. GES-OFF 378.6 +/- 87.4, P < 0.05). Elastase was lower in medication NR and RES than in normal controls. Postprandial pancreatic polypeptide was greater with GES ON than OFF (P = 0.07). HRV revealed a lower percentage of change with device ON versus OFF (44.2 +/- 5.5 vs. 48.5 +/- 5.2, P = 0.08) and lower TSS with ON versus OFF (15.9 +/- 4.5 vs. 25.7 +/- 5.3, P < 0.05). CONCLUSIONS: GES improves exocrine pancreatic release, effects autonomic control, and improves GI symptoms, suggesting a possible role for GES in the treatment of pancreatic insufficiency associated with gastroparesis.

Alteration of the counterregulatory responses to insulin-induced hypoglycemia and of cognitive function after massive weight reduction in severely obese subjects.

The autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis are reported as activated in excess in the morbidly obese state and, therefore, changes after weight loss can be anticipated. The aim of this study was to investigate the impact of a massive (approximately 30%) weight reduction on the activation of the HPA axis and the ANS following bariatric surgery. Eight (7 women, 1 man) severely obese (125+/-12 kg; body mass index [BMI], 45+/-4 kg/m2) nondiabetic subjects, underwent a 3-hour hyperinsulinemic (1,034 pmol/kg/h) glucose clamp study at hypoglycemia of arterial B-glucose concentration of 3.4 mmol/L. Cognitive function was evaluated by a visuospatial computerized problem-solving test, the Perceptual Maze Test (PMT). The mean weight loss was 40+/-9 kg approximately 12 months postsurgery when their weight was stabilized (85+/-6 kg; BMI, 31+/-3 kg/m2), and insulin sensitivity improved to an average increase of 376%+/-250% (P<.01) of initial value. Before weight reduction, all patients demonstrated brisk peak responses in glucagon, epinephrine, pancreatic polypeptide (PP), norepinephrine, and cortisol, indicative of preserved or exaggerated activation of ANS and HPA axis. In the reduced-obese state, all these responses were attenuated and most markedly so for glucagon, which was totally abolished. In contrast, the growth hormone (GH) response was increased after weight reduction. The cognitive function was clearly modified by weight reduction both during normoglycemia and hypoglycemia and was changed preferentially to a speed-preferring strategy in the reduced-obese state compared with a more accuracy preferred problem-solving process of PMT test presurgery. These results demonstrate a reduction of the glucose counterregulatory hormonal responses, increased insulin sensitivity, and perturbed cognitive function after massive weight reduction. It may be speculated on if the increased insulin sensitivity and reduced counterregulation to hypoglycemia could predispose to low plasma glucose concentrations.

Atropine-induced gastric dysrhythmia is not normalized by electroacupuncture.

Acupuncture has been shown to improve the regularity of gastric myoelectric activity. The aim of this study was to evaluate whether atropine-induced gastric dysrhythmia can be normalized by electroacupuncture. Fifteen healthy male volunteers were enrolled for this study. Each subject was studied for three sessions in a randomized sequence which included electroacupuncture on the Zusanli (St 36) points with or without premedication with atropine and a placebo stimulation on a nonacupoint. Cutaneous EGG was performed for 30 min at the baseline, 30 min during acupuncture, and for an additional 30 min after acupuncture. Serum gastrin, motilin, and human pancreatic polypeptide (hPP) levels were also measured. When applying 2 Hz of electrical stimulation on the Zusnali point, there was a significant increase in the percentage of normal frequency (2-4 cpm) during acupuncture (baseline versus acupuncture, 82.09 +/- 12.37% versus 93.08 +/- 8.17%, P < 0.01). There was a significant decrease in the percentage of bradygastria as well as tachygastria during 2 Hz of electrical stimulation on the Zusnali point. Using intravenous atropine immediately before electroacupuncture, the percentage of normal frequency during acupuncture and postacupuncture periods decreased significantly (baselines versus acupuncture and postacupuncture, 83.86 +/- 13.79% versus 55.07 +/- 29.44% and 56.76 +/- 33.44%, P < 0.01). There was a significant decrease in serum PP after intravenous atropine. This observation indicated that atropine-induced gastric dysrhythmia might be mediated partly via the vagal pathway. However, atropine-induced gastric dysrhythmia is not normalized by electroacupuncture.

Important role of hypothalamic Y2 receptors in body weight regulation revealed in conditional knockout mice.

Neuropeptide Y is implicated in energy homeostasis, and contributes to obesity when hypothalamic levels remain chronically elevated. To investigate the specific role of hypothalamic Y2 receptors in this process, we used a conditional Y2 knockout model, using the Cre-lox system and adenoviral delivery of Cre-recombinase. Hypothalamus-specific Y2-deleted mice showed a significant decrease in body weight and a significant increase in food intake that was associated with increased mRNA levels for the orexigenic NPY and AgRP, as well as the anorexic proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) in the arcuate nucleus. These hypothalamic changes persisted until at least 34 days after Y2 deletion, yet the effect on body weight and food intake subsided within this time. Plasma concentrations of pancreatic polypeptide and corticosterone were 3- to 5-fold increased in hypothalamus-specific Y2 knockout mice. Germ-line Y2 receptor knockout also produced a significant increase in plasma levels of pancreatic polypeptide. However, these mice differed from conditional knockout mice in that they showed a sustained reduction in body weight and adiposity associated with increased NPY and AgRP but decreased POMC and CART mRNA levels in the arcuate nucleus. The transience of the observed effects on food intake and body weight in the hypothalamus-specific Y2 knockout mice, and the difference of this model from germ-line Y2 knockout mice, underline the importance of conditional models of gene deletion, because developmental, secondary, or extrahypothalamic mechanisms may mask such effects in germ-line knockouts.

Effect of electrical stimulation on acupuncture points in diabetic patients with gastric dysrhythmia: a pilot study.

BACKGROUND/AIMS: Abnormal gastric slow-wave frequencies have been observed in diabetic gastroparesis and are associated with impaired antral motor activity. In this study, we aimed at evaluating the effect of acupuncture on gastric slow waves in diabetic patients with symptoms suggesting gastric motor dysfunction. METHODS: Fifteen patients with type II diabetes who had had dyspeptic symptoms for more than 3 months were enrolled. Two acupuncture needles were inserted into the subjects' legs at the Zusanli points, and electrical stimulation (2-Hz pulses) was delivered for 30 min. Cutaneous electrogastrography was performed for 30 min at baseline, for 30 min during acupuncture, and for an additional 30 min after acupuncture. Serum gastrin, motilin, and human pancreatic polypeptide levels were also measured. RESULTS: There was a significant increase in the percentages of normal frequency during and after acupuncture (baseline vs. acupuncture and after acupuncture 21.99 +/- 19.38% vs. 45.93 +/- 19.72 and 48.92 +/- 19.56%; p < 0.01). In addition, the percentage of tachygastric frequency was decreased significantly during and after acupuncture. The dominant frequency was also changed significantly. There was an increase of serum human pancreatic polypeptide during acupuncture (baseline vs. acupuncture 56.96 +/- 27.64 vs. 73.11 +/- 22.37 pmol/l; p < 0.05). CONCLUSIONS: The results of this study revealed that electrical stimulation at the Zusanli points could increase the percentage of normal electrogastrography frequency and decrease the percentage of tachygastric frequency in diabetic patients. The data indicate that acupuncture may enhance the regularity of gastric myoelectrical activity in diabetic patients.

Cholecystokinin mediates depression of feed intake in dairy cattle fed high fat diets.

Two experiments were conducted to investigate the effects of 1) different concentrations of dietary fat and 2) i.v. administration of a cholecystokinin receptor antagonist (MK-329) on feed intake and plasma concentrations of hormones and metabolites in dairy cattle. In Experiment 1, 4 lactating Holstein cows were used in a 4 x 4 Latin square design. Treatments were diets with 1) no fat added, 2) 30 g fat/kg feed (calcium salts of long-chain fatty acids as fat supplement), 3) 60 g fat/kg, and 4) 90 g fat/kg added. Cows were fed once daily a diet of concentrate, corn silage, alfalfa haylage, and alfalfa pellets. Dry matter intake decreased linearly with increasing concentrations of dietary fat (P < 0.0001). Overall plasma concentrations of nonesterified fatty acids (P < 0.0001), triacylglycerol (P < 0.0006), and cholecystokinin (P < 0.02), increased linearly with each level of dietary fat, but there was a linear decrease in plasma insulin (P < 0.0008). In Experiment 2, 4 nonpregnant and nonlactating Holstein heifers were used in a cross-over design in a 2 x 2 factorial arrangement of treatments. Treatments were diet (fatty acids, 27 g/kg vs 103 g/kg diet dry matter) and i.v. injections (MK-329 vs vehicle). Heifers were fed once daily a total mixed ration of corn silage, cracked corn and soybean meal with or without fat supplement. Diets were switched by period and either MK-329 (70 microg/kg body weight) or its vehicle was injected i.v. at 2 hr postfeeding. Daily dry matter intake was decreased by feeding the high fat diet (P < 0.02) but was not affected by injections. Injection of MK-329, however, increased dry matter intake by 92% in heifers fed the high fat diet during the first 2 hr postinjection compared to vehicle injection. Plasma pancreatic polypeptide concentration was increased by the high fat diet at 2 hr postfeeding (P < 0.02) but was lowered by MK-329 at 1 hr postinjection (P < 0.001). Plasma insulin was lowered by the high fat diet (P < 0.01) but was not affected by injections. The elevated plasma cholecystokinin concentration may have mediated depressed feed intake of dairy cattle fed the high fat diets.

Efficacy and effect of SI17 therapy on pancreatic polypeptide in vascular and tension-type headache.

BACKGROUND AND PURPOSE: Vascular and tension-type headache is most commonly encountered, and SI17 therapy has been tested to treat headache with good results. The efficacy of SI17 therapy for vascular and tension-type headache was compared and the effect of SI17 therapy on pancreatic polypeptide (PP) was studied. MATERIALS AND METHODS: 29 cases of vascular headache (20 cases in acute attack during the trial) and 27 cases of tension-type headache (19 cases in acute attack) were enrolled in the study. Plasma PP level before and 4th day after treatment was measured by radioimmunoassay. RESULTS: SI17 therapy is better for the treatment of vascular headache. Vascular headache with higher PP level and tension-type headache with normal PP level had good therapeutic results. CONCLUSION: The clinical efficacy is better for vascular headache with the increase of vagus tension and for tension-type headache with normal vagus tension.

Antroduodenal motility in chronic pancreatitis: are abnormalities related to exocrine insufficiency?

In patients with chronic pancreatitis (CP) the relation among exocrine pancreatic secretion, gastrointestinal hormone release, and motility is disturbed. We studied digestive and interdigestive antroduodenal motility and postprandial gut hormone release in 26 patients with CP. Fifteen of these patients had pancreatic insufficiency (PI) established by urinary para-aminobenzoic acid test and fecal fat excretion. Antroduodenal motility was recorded after ingestion of a mixed liquid meal. The effect of pancreatic enzyme supplementation was studied in 8 of the 15 CP patients with PI. The duration of the postprandial antroduodenal motor pattern was significantly (P < 0.01) prolonged in CP patients (324 +/- 20 min) compared with controls (215 +/- 19 min). Antral motility indexes in the first hour after meal ingestion were significantly reduced in CP patients. The interdigestive migrating motor complex cycle length was significantly (P < 0.01) shorter in CP patients (90 +/- 8 min) compared with controls (129 +/- 8 min). These abnormalities were more pronounced in CP patients with exocrine PI. After supplementation of pancreatic enzymes, these alterations in motility reverted toward normal. Digestive and interdigestive antroduodenal motility are abnormal in patients with CP but significantly different from controls only in those with exocrine PI. These abnormalities in antroduodenal motility in CP are related to maldigestion.

Effects of electro-acupuncture on somatostatin and pancreatic polypeptide in ischemic cerebrovascular diseases.

The levels of somatostatin (SS) in CSF and blood and pancreatic polypeptide (PP) in plasma were measured by radioimmunoassay in 64 patients with acute ischemic cerebrovascular diseases (ICVD), randomly divided into two groups: group 1 (n = 31, both electro-acupuncture and routine treatments given) and group 2 (n = 33, routine treatment) and 26 non-ICVD patients were used as controls. The points of electro-acupuncture were Quchi (LI 12), Waiguan (SJ 5) and Huantiao (GB 30) and Zusanli (St 36). After a course of treatment, the SS levels in plasma and CSF were significantly increased in the patients of group 1 with good result and their plasma PP level had no significant change. In the patients with poor result, however, the PP level was significantly decreased. The results suggested that electro-acupuncture might play an active role in alleviating the SS metabolic disturbance in CNS of ICVD patients.

Effect of processed and non-processed coffee samples on gastric potential difference. Study with healthy male Helicobacter pylori-positive and Helicobacter pylori-negative volunteers.

In an open trial with 18 healthy male volunteers (21-45 years old) the effect of processed (test) and non-processed (reference) coffee samples of same origin on the gastric potential difference (GPD) was studied. Test coffee samples were processed with the patented "Darboven improvement procedure" before roasting. All treatment groups were subdivided according to the Helicobacter pylori status of the volunteers. The evaluation of the target parameters Reizindex (RI), area under the baseline (AUB), maximum potential difference (Pdmax) and total time (ttot) revealed a significant lower RI (p = 0.0282) and AUB (p = 0.0136), and a significant shorter ttot (p = 0.0286) for the processed coffee. Total cholesterol, high-density lipoprotein (HDL) cholesterol, and pancreatic peptides showed a comparable marked increase of the arithmetic mean with both coffee samples, however, being more intense in the Helicobacter pylori-positive subgroup than in the Helicobacter pylori-negative subgroup. No negative findings concerning tolerability and safety could be seen. In conclusion, the test coffee samples processed with a new method to improve the stomach mucosal irritation-potential of coffee charges revealed a remarkably lower stomach mucosal irritation.

Differences in cholecystokinin release and gallbladder contraction between emulsified and nonemulsified long-chain triglycerides.

BACKGROUND: Fat is a potent stimulus of cholecystokinin (CCK) release. Apart from lipolysis, fatty acid chain length, and saturation, emulsification may also determine the magnitude of CCK release. METHODS: We have studied the effect of emulsification of soybean oil on CCK and pancreatic polypeptide (PP) release (radioimmunoassay [RIA]) and gallbladder motility (ultrasonography). Six healthy subjects were studied on three separate occasions in random order during (1) intraduodenal administration of emulsified long-chain triglycerides (LCT) (6 mmol/h for 120 minutes); (2) equimolar amounts of nonemulsified LCT with addition of emulsifier; and (3) saline with emulsifier (control). RESULTS: Intraduodenal administration of both nonemulsified LCT and emulsified LCT induced significant (p < .05) increases in plasma CCK and PP levels and reductions in gallbladder volume. However, compared with nonemulsified LCT, emulsified LCT resulted in a readier and significantly stronger CCK release (212+/-62 pmol/L per 120 minutes vs 36+/-7 pmol/L per 120 minutes; p < .05); PP release (2034+/-461 pmol/L per 120 minutes vs 671+/-106 pmol/L per 120 minutes; p < .05); and gallbladder contraction (77%+/-2% vs 41%+/-7%; p < .05). No significant alterations were observed in plasma CCK or PP levels and gallbladder volume during administration of saline with emulsifier. CONCLUSIONS: Intraduodenal administration of a low-dose emulsified LCT more potently stimulates CCK and PP release and gallbladder contraction in comparison to equimolar amounts of nonemulsified LCT. These findings point to an important role for solubilization of LCT in determining the magnitude of CCK release from the intestine.

High fat diets increase plasma cholecystokinin and pancreatic polypeptide, and decrease plasma insulin and feed intake in lactating cows.

High fat diets often decrease feed intake in dairy cows; however, mechanisms underlying fat-induced depression of feed intake are yet to be established. The postulate that high fat diets decrease feed intake by increasing concentrations of lipid metabolites or satiety hormones in blood was tested by using eight multiparous Holstein cows in a simultaneously replicated 4 x 4 Latin-square design. Treatments were control diet with 1) no fat added, 2) 30 g/kg calcium salts of long-chain fatty acids, 3) 60 g/kg calcium salts of long-chain fatty acids, and 4) 90 g/kg calcium salts of long-chain fatty acids. Cows were fed once daily a diet of concentrate, corn silage, alfalfa haylage and alfalfa hay (50:25:14:11 on a dry matter basis). Dry matter and energy intakes were decreased by inclusion of calcium salts of long-chain fatty acids >30 g/kg of total diet dry matter (P = 0.0001). Plasma nonesterified fatty acids and triglyceride concentrations were increased linearly by feeding increasing amounts of fat (P < 0.003 and P = 0.0001, respectively), whereas plasma beta-hydroxybutyrate and glucose concentrations were not influenced by supplemental fat. Fat supplementation increased postfeeding plasma cholecystokinin concentrations and linearly increased plasma pancreatic polypeptide concentrations. Highest concentrations of plasma cholecystokinin (P < 0.001) and pancreatic polypeptide (P < 0.05) were observed in cows fed the 90 g/kg fat supplement. Plasma insulin was lowered linearly by feeding fat (P = 0.0001). Increased concentrations of cholecystokinin and pancreatic polypeptide were associated with decreased intakes of feed and energy, whereas insulin may not be involved in the control of feed intake in cows fed fat.

Decreased plasma levels of cholecystokinin in healthy males after chronic ingestion of a heat-treated soya product.

Administration of raw soya containing a trypsin inhibitor stimulated excessive release of cholecystokinin (CCK) which led to pancreatic hypertrophy, hyperplasia and cancer in the rats (Booth et al. (1964) Proc. Soc. Exp. Biol. Med., 116, 1067). More postprandial CCK release in healthy humans was observed after ingestion of a single dose of raw soya than heat-treated soya (Calam et al. (1989) Br. J. Nutr., 58, 175). The effect of chronic ingestion of a heat-treated soya product on postprandial CCK release was investigated in six healthy adult males after ingestion of a 36-oz. portion of soymilk daily for 1 month and at 2-3 months after termination of soymilk ingestion. Subjects fasted for 15 h, ingested Lipomul (1.5 g/kg) and provided blood at timed intervals for CCK analysis. The results show that 1-month ingestion of soymilk decreased the magnitude of Lipomul-induced postprandial CCK release in plasma of all six subjects by 5-60% (P < 0.05) compared to those obtained at 2-3 months after the withdrawal from soymilk ingestion. Plasma pancreatic polypeptide (PP) levels were similarly decreased in five of the six subjects by 19-67% (P = 0.03) in line with the regulation of PP by CCK. Thus, prolonged exposure of humans to a heat-treated soya inhibited slightly meal-induced CCK release in contrast to that found in rats after raw soya diets.

Intraluminal ileal recovery of pancreatic polypeptide.

Pancreatic polypeptide (PP) is a normal constituent of pancreatic islet cells. Enterocytes containing PP have been identified but incompletely characterized. We previously demonstrated independent intravascular and intraluminal release of two related peptides, peptide YY and neuropeptide Y. In this study, using ileal segments in conscious dogs, we evaluated the intravascular and ileal intraluminal presence of PP to test meals. Fasted plasma and recoverable ileal PP concentrations averaged 139 +/- 2 and 65 +/- 4 pg/mL, respectively. A mixed protein meal resulted in a sustained rise of circulating PP levels associated with a brief evaluation of ileal luminal PP levels. Fat meals were followed by elevations in plasma PP levels without luminal changes. Glucose ingestion altered neither plasma nor luminal PP levels. Our data support the existence of ileal PP-containing cells that respond independently of circulatory PP-releasing cells to different ingested stimuli.

[Increase of energy expenditure in Parkinson's disease]. / Augmentation de la dépense énergétique au cours de la maladie de Parkinson.

Energy expenditure was determined in 18 patients with Parkinson's disease, 6 healthy volunteers and 6 patients with essential tremor, age-matched, using the indirect calorimetric method which measures the gas exchange rate. The results showed a significant increase in the relative energy expenditure, i.e. the difference between absolute and predictable values from the Harris and Benedict equation, among the parkinsonian patients (+21 +/- 4.1 p. 100; mean +/- S.E.M.) as compared to the 2 control groups (-8.6 +/- 7 p. 100 and -2.1 +/- 4.1 p. 100 respectively; p less than 0.001). There was no correlation between the rate of energy expenditure and the duration or degree of severity of the disease, and particularly the occurrence and magnitude of weight loss, which is frequently observed during the course of the disease. The relative energy expenditure was not significantly different between untreated and treated parkinsonian patients (18.8 +/- 3 p. 100 and 24.5 +/- 6.2 p. 100 respectively). Further investigations were designed to determine whether the increased energy expenditure could reflect a functional impairment of the automatic nervous system. The integrity of the vagus nerve was tested by plotting vs time the plasma Pancreatic Polypeptide levels in response to insulin-induced hypoglycaemia. A physiological stimulation was obtained in the 8 parkinsonian patients studied. This is not the case in chronic autonomic failure. On the contrary, the relative energy expenditure was significantly decreased in the 6 patients that were given a beta-blocking drug, pindolol, 15 mg daily for 3 weeks (+30.7 +/- 4.3 p. 100 before and +21 +/- 4.2 p. 100 after treatment; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)