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At least 451 records · Page 25Linked to original sources
PubMed1995

Biology of enterostatin. II. Development of enzyme-linked immunosorbentassay (ELISA) for enterostatin (Val-Pro-Asp-Pro-Arg), the procolipase activation peptide.

Enterostatins belong to a family of pentapeptides (e.g., Val-Pro-Asp-Pro-Arg in pig, horse, dog, and rat; Ala-Pro-Gly-Pro-Arg in human and chicken; and Val-Pro-Gly-Pro-Arg in rat) derived from the amino-terminus of procolipase after the action of trypsin. Pharmacologic studies with Val-Pro-Asp-Pro-Arg have suggested a role for this peptide in appetite regulation and pancreatic insulin secretion. Studies into the distribution of enterostatins or the role of endogenous peptides have not been possible due to the lack of a suitable method for enterostatin assay. To this end, we raised a highly specific antibody and developed an enzyme-linked immunosorbent assay for Val-Pro-Asp-Pro-Arg. Using the newly developed assay we have shown the presence of Val-Pro-Asp-Pro-Arg-like immunoreactivity (2455 +/- 440 pmol/g) in the rat brain.

Amino Acid Sequence↗
PubMed1993

Crystallization of pancreatic procolipase and of its complex with pancreatic lipase.

The human pancreatic lipase-porcine procolipase complex has been crystallized in space group P3(2)21 (a = b = 80.3 A and c = 251 A) from a solution containing polyethylene glycol, NaCl and beta-octyl glucoside. The crystals diffract to 2.6 A on a synchrotron beam. The complex in the presence of bile salts and phospholipids crystallizes in a tetragonal space group P4(2)2(1)2 (a = b = 133.4 A, c = 92.6 A). Crystals of procolipase alone were obtained under slightly different experimental conditions (space group I432, a = b = c = 164.3 A).

Animals↗
PubMed1994

Enterostatin inhibits insulin secretion from isolated perifused rat islets.

The effect of enterostatin on glucose-induced insulin secretion was examined in isolated, perifused rat islets. In the presence of 16.67 mM glucose, there was significant inhibition of insulin secretion at concentrations of 200 nM, 2, 20 and 40 microM enterostatin. In particular, the second phase of insulin secretion was inhibited. With a low concentration of glucose (2.78 mM), there was no significant effect on insulin secretion by enterostatin. The inhibition of insulin secretion exerted by enterostatin may be an important effect in the prevention of insulin resistance.

Animals↗
PubMed2002

Regulation of feeding behavior, gastric emptying, and sympathetic nerve activity to interscapular brown adipose tissue by galanin and enterostatin: the involvement of vagal-central nervous system interactions.

Galanin and enterostatin, which are distributed in both the central nervous system and the gastrointestinal tract, regulate the feeding behavior. In the first set of experiments, we investigated the effects of galanin and enterostatin, injected into the third ventricle, on food intake, gastric emptying, and the sympathetic activity of nerves innervating interscapular brown adipose tissue in rats. Galanin dose-dependently increased the intake of a high-fat diet after overnight starvation, but it did not affect low-fat diet intake. In contrast, enterostatin suppressed the intake of the high-fat diet, while intake of the low-fat diet was not affected. Galanin significantly and dose-dependently suppressed gastric emptying rate. However, gastric emptying showed no response to enterostatin. Galanin produced a dose-dependent suppression of sympathetic firing rate. In rats fed a high-fat diet, the injection of enterostatin showed a dose-dependent increase in firing rate. In contrast, animals fed a chow diet showed almost no response. In the second set of experiments, we investigated the role of the hepatic vagus nerve in modulating the peripheral response to enterostatin in rats. Intraperitoneal (i.p.) enterostatin reduced the intake of a high-fat diet. Immunohistochemical identification indicated that the Fos protein was present in the nucleus tractus solitarius, and parabrachial, paraventricular, and supraoptic nuclei after IP enterostatin. These responses to i.p. enterostatin were blocked by hepatic vagotomy. These results suggest that galanin and enterostatin coordinate to regulate feeding behavior, gastric emptying, and sympathetic activity to interscapular brown adipose tissue via central and peripheral sites of action, one of which was the interaction which was found to exist through the vagal system.

Adipose Tissue, Brown↗
PubMed2001

Determination of enterostatin in human cerebrospinal fluid by capillary electrophoresis with laser induced fluorescence detection.

A capillary electrophoresis (CE) method with laser induced fluorescence (LIF) detection is described for quantification of enterostatin (Val-Pro-Asp-Pro-Arg), a pentapeptide involved in appetite regulation and insulin secretion. Enterostatin and two other pentapeptides belonging to the enterostatin family (i.e. Ala-Pro-Gly-Pro-Arg and Val-Pro-Gly-Pro-Arg) were well separated from each other. The peptides were fluorescently tagged with naphthalene-2,3- dicarboxaldehyde (NDA) and separated by micellar electrokinetic chromatography (MEKC) in the presence of methanol as an organic modifier. Coupled with LIF detection, the method had a detection limit of 4.8 x 10(-6) M for enterostatin. The relative standard deviation was to be 4.0% from five determinations of enterostatin at 37.2 microM in a human cerebrospinal fluid (CSF) sample. Twenty-three human CSF samples were analyzed. The level of enterostatin ranged from 24 microM to 51 microM with a mean (+/- SEM) value of 41.7 +/- 2.0 microM.

Amino Acid Sequence↗
PubMed2003

DNA polymorphisms of lipase related genes.

We previously determined sequenced the PNLIP gene encoding pancreatic lipase in cell lines of subjects with clinical deficiency of pancreatic lipase (MIM 246600) and found no putative disease-causing mutations. As part of the ongoing analysis of the genomic DNA of these subjects, we now report the development of genomic amplification primers to sequence the coding regions of CLPS, CEL, PLRP1, and PLRP2, encoding pancreatic co-lipase, carboxyl-ester lipase, and pancreatic-lipase-related proteins-1 and -2, respectively. Whereas we found no putative disease-causing missense or nonsense mutations in these samples, we discovered a total of 13 common polymorphisms (12 single nucleotide polymorphisms) in these four genes. Genotypes of these polymorphisms may be useful in future association analyses.

Carboxylesterase↗
PubMed2007

Human pancreatic digestive enzymes.

A primary function of the pancreas is to produce digestive enzymes that are delivered to the small intestine for the hydrolysis of complex nutrients. Much of our understanding of digestive enzymes comes from studies in animals. New technologies and the availability of the sequence of the human genome allow for a critical review of older reports and assumptions based on animal studies. This report updates our understanding of human pancreatic digestive enzymes with a focus on new insights into the biology of human proteases, lipases and amylases.

Amylases↗
PubMed1994

The activation of porcine pancreatic lipase by cis-unsaturated fatty acids.

In the presence of taurodeoxycholate, cis-unsaturated fatty acids increase porcine pancreatic lipase activity 15-fold at pH 7.5. This effect is saturable with a low proportion of fatty acid to substrate. The overall angle of the fatty acid, the position of its double bond and the presence of a carboxyl group were critical factors in whether the fatty acid effectively increased lipase activity. When the substrate is emulsified by taurodeoxycholate, the pH optimum for lipase ranges from 6.2 to 7.0. In the presence of cis-unsaturated fatty acids, the overall activity of lipase increases, the pH optimum shifts, and the pH-activity curve becomes biphasic, with one optimum around pH 7.7, and the other around pH 8.8. Fluorescence studies indicate that fatty acids bind near aromatic residues in lipase, particularly tryptophan. Using the fluorescent fatty acid cis-parinaric acid, it was determined that multiple binding sites are present with Kd values of approx. 10(-6) M. Far-UV circular dichroism (CD) studies indicate that in addition to a high affinity fatty acid binding site with a Kd of approx. 10(-6) M, there is also a low affinity binding site with a Kd of approx. 10(-4) M. The far-UV CD data also show that cis-unsaturated fatty acids change the conformation of lipase. It is calculated that the percentage of alpha helix decreases, and the amount of beta sheet and beta turn structure increases. Because the three-dimensional crystal structure of lipase is known, a model is proposed to describe how cis-unsaturated fatty acids increase lipase activity.

Animals↗
PubMed1995

Differential effects of enterostatin, galanin and opioids on high-fat diet consumption.

Enterostatin, the activation peptide of pancreatic procolipase, suppresses high-fat diet consumption both centrally and peripherally. kappa-opioid agonists are also known to stimulate fat intake. These experiments were conducted to determine if an opioidergic central pathway might mediate the effects of enterostatin and galanin on fat intake. Male Sprague-Dawley rats were adapted to a high-fat diet (56% energy) and were implanted with cannulae aimed at the lateral cerebral ventricle (LV) or third cerebral ventricle (3V). Injection of enterostatin (1 nmol, LV) suppressed high-fat diet consumption in fasted (20 h) rats. This inhibition of high-fat intake by enterostatin was attenuated by central injection of the specific kappa-agonist U50488 (2.15, 21.5 and 215 nmol, LV) in a dose-dependent manner in fasted rats while only the highest dose of U50488 (215 nmol, LV) independently produced stimulation of high-fat diet consumption in sated rats. Galanin (0.1 nmol, 3V) induced consumption of high-fat diet in sated rats similar to that seen with U50488 and this stimulation was attenuated by peripheral injection of naloxone (1.0 mg/kg i.p.). We present a model which integrates the present data, as well as previous findings, in explaining a potential common opioid pathway modulating fat consumption.

Animals↗
PubMed1996

Effect of galanin and enterostatin on sympathetic nerve activity to interscapular brown adipose tissue.

The effects of galanin and enterostatin on sympathetic activity have been examined in rats using electrophysiological techniques. Galanin, in doses of 25-300 pmol, and enterostatin, in doses of 0.5-10 nmol, were injected into the third ventricle of anesthetized male Sprague-Dawley rats in 1-microliter volumes. Galanin produced a dose-dependent suppression (ranging between 20 and 80%) of sympathetic firing rate of nerves innervating interscapular brown adipose tissue. In rats fed a chow diet, injection of enterostatin produced only a transient 10% rise in firing rate which returned to baseline within 10-15 min. In contrast, animals fed a high-fat diet showed a dose-dependent increase in firing rate lasting for 60 min. The results of this experiment are consistent with the hypothesis that food intake and sympathetic nervous system activity have a reciprocal relationship. The implications of this relationship are discussed.

Adipose Tissue, Brown↗
PubMed1994

Individual differences in the macronutrient preference profile of outbred rats: implications for nutritional, metabolic, and pharmacologic studies.

While screening outbred male Holtzman Sprague-Dawley rats for their macronutrient (protein, carbohydrate, and fat) preferences, we noticed substantial group-to-group variation in the preference profile. This led us to analyze preference data on two hundred and seventy rats collected over a three-year period to determine whether preferences could be predicted. The results led us to conclude that observed variations in macronutrient preference profiles may be secondary to genetic heterogeneity in the outbred population. We have also shown that the outcome of the pharmacologic effects of two agents (insulin and enterostatin) on appetitive behavior will vary from animal to animal within a single group. Accordingly, researchers must be aware that the breeding history of the laboratory animal is a major factor in the outcome of the experiment and interpretation of the findings.

Animal Nutritional Physiological Phenomena↗