GLP-1 and GIP are colocalized in a subset of endocrine cells in the small intestine

BACKGROUND: The incretin hormones GIP and GLP-1 are thought to be produced in separate endocrine cells located in the proximal and distal ends of the mammalian small intestine, respectively. METHODS AND RESULTS: Using double immunohistochemistry and in situ hybridization, we found that GLP-1 was colocalized with either GIP or PYY in endocrine cells of the porcine, rat, and human small intestines, whereas GIP and PYY were rarely colocalized. Thus, of all the cells staining positively for either GLP-1, GIP, or both, 55-75% were GLP-1 and GIP double-stained in the mid-small intestine. Concentrations of extractable GIP and PYY were highest in the midjejunum [154 (95-167) and 141 (67-158) pmol/g, median and range, respectively], whereas GLP-1 concentrations were highest in the ileum [92 (80-207) pmol/l], but GLP-1, GIP, and PYY immunoreactive cells were found throughout the porcine small intestine. CONCLUSIONS: Our results provide a morphological basis to suggest simultaneous, rather than sequential, secretion of these hormones by postprandial luminal stimulation.     

The reduction in hepatic insulin clearance after oral glucose is not mediated by gastric inhibitory polypeptide (GIP)

Since the C-peptide/insulin ratio is reduced after oral glucose ingestion, the incretin hormone gastric inhibitory polypeptide (GIP) has been assumed to decrease hepatic insulin extraction. It was the aim of the present study to evaluate the effects of GIP on insulin extraction. Seventy-eight healthy subjects (27 male, 51 female, 43+/-11 years) were subjected to (a). an oral glucose tolerance test and (b). an intravenous injection of 20 pmol GIP/kg body weight, with capillary and venous blood samples collected over 30 min for insulin, C-peptide and GIP (specific immunoassays). Following GIP administration, plasma concentrations of total and intact GIP reached to peak levels of 80+/-7 and 54+/-5 pmol/l, respectively (p<0.0001). The rise in insulin after oral glucose and after intravenous GIP administration significantly exceeded the rise in C-peptide (p<0.0001). Estimating insulin extraction from the total integrated insulin and C-peptide concentrations (AUCs), only the oral glucose load (p<0.0001), but not the intravenous GIP administration (p=0.18) significantly reduced insulin clearance. Therefore, insulin clearance is reduced after an oral glucose load. This effect does not appear to be mediated by GIP.     

Reduced accumulation of specific microRNAs in colorectal neoplasia

Short non-coding RNAs are known to regulate cellular processes including development, heterochromatin formation, and genomic stability in eukaryotes. Given the impact of these processes on cellular identity, a study was undertaken to investigate possible changes in microRNA (miRNA) levels during tumorigenesis. A total of 28 different miRNA sequences was identified in a colonic adenocarcinoma and normal mucosa, including 3 novel sequences and a further 7 that had previously been cloned only from mice. Human homologues of murine miRNA sequences, miR-143 and miR-145, consistently display reduced steady-state levels of the mature miRNA at the adenomatous and cancer stages of colorectal neoplasia.     

GLP-2 stimulates intestinal growth in premature TPN-fed pigs by suppressing proteolysis and apoptosis

We wished to determine whether exogenous glucagon-like peptide (GLP)-2 infusion stimulates intestinal growth in parenterally fed immature pigs. Piglets (106-108 days gestation) were given parenteral nutrient infusion (TPN), TPN + human GLP-2 (25 nmol. kg(-1). day(-1)), or sow's milk enterally (ENT) for 6 days. Intestinal protein synthesis was then measured in vivo after a bolus dose of [1-(13)C]phenylalanine, and degradation was calculated from the difference between protein accretion and synthesis. Crypt cell proliferation and apoptosis were measured in situ by 5-bromodeoxyuridine (BrdU) and terminal dUTP nick-end labeling (TUNEL), respectively. Intestinal protein and DNA accretion rates and villus heights were similar in GLP-2 and ENT pigs, and both were higher (P < 0.05) than in TPN pigs. GLP-2 decreased fractional protein degradation rate, whereas ENT increased fractional protein synthesis rate compared with TPN pigs. Percentage of TUNEL-positive cells in GLP-2 and ENT groups was 48 and 64% lower, respectively, than in TPN group (P < 0.05). However, ENT, but not GLP-2, increased percentage of BrdU-positive crypt cells above that in TPN piglets. We conclude that GLP-2 increases intestinal growth in premature, TPN-fed pigs by decreasing proteolysis and apoptosis, whereas enteral nutrition acts via increased protein synthesis and cell proliferation and decreased apoptosis.     

The intercellular adhesion molecule-1 K469E polymorphism in type 1 diabetes

Type 1 (insulin-dependent) diabetes is a complex trait. The region harboring the ICAM1 gene on 19p13 links to type 1 diabetes, and a growing body of evidence indicates that intercellular adhesion molecule-1 (ICAM-1) could play a role in type 1 diabetes development. Recently, association studies of an ICAM-1 K469E polymorphism in type 1 diabetes populations have reported conflicting results. Hence, we performed a transmission disequilibrium test analysis of the ICAM-1 K469E variations in 253 Danish type 1 diabetes families. Linkage and association was not found between the ICAM-1 K469E variation and type 1 diabetes in Danish patients (P(tdt)> or =0.48), and our data did not indicate an interaction between ICAM1 and IDDM1 in predisposition to type 1 diabetes in Danes (P=0.78). We did not observe significant association with late-onset type 1 diabetes (P(tdt)> or =0.12) or differences in transmission patterns between groups of affected offspring stratified for age at onset (P> or =0.19), as suggested in Japanese patients. Combined analysis of the present and previously reported transmission data comprising 728 affected offspring of Romanian, Finnish, and Danish ancestry suggested association between the ICAM-1 E469 allele and type 1 diabetes (P(tdt)=0.013), but association was not found in the combined Scandinavian material. In conclusion, we found no association of the ICAM-1 K469E polymorphism with type 1 diabetes or its subsets stratified for age at onset and HLA risk in Danish patients. Analysis of ICAM-1 K469E transmissions reported in three populations suggested association to type 1 diabetes, but also demonstrated heterogeneity between populations.     

Evaluation of sequential sampling plans for the larger grain borer (Coleoptera: Bostrichidae) and the maize weevil (Coleoptera: Curculionidae) and of visual grain assessment in West Africa

Repeated sampling of rural maize stores in Benin was conducted to evaluate published parameters of a sequential sampling plan for a negative binomial distribution to determine pest status for Prostephanus truncatus (Horn) and Sitophilus zeamais Motschulsky. A computer program was used to rerandomize the data and evaluate the effects, in terms of average sample number and error rates, of different sampling plan parameter values. With respect to P. truncatus, lower and upper thresholds of 0.2 and 1.0 insects per ear and parameter values of k = 0.2 and alpha = beta = 0.1 were found to be adequate. With respect to S. zeamais, lower and upper thresholds of 10 and 20 insects per ear and parameter values of k = 1.0 and i alpha = beta = 0.1 were found to be adequate. Simplified sampling rules were proposed in which 11 ears should be sampled and if no P. truncatus are found, the population is low; otherwise the Wald plan should be followed. Owing to the lower per capita rate of damage, effective simplified sampling rules for S. zeamais were difficult to construct. An evaluation of the visual assessment scale rising whole ears showed that a visual scale estimating percentage damage rather than percentage loss, might be easy to construct and preferable for traders. Further work is needed to improve the usefulness of the visual scale in pest management decision support.     

Sperm binding capacity and ultrastructure of the zona pellucida of stored canine oocytes

Sperm binding to the zona pellucida is a prerequisite for fertilization, and tests that evaluate this function have been described for several species. When carrying out such tests in the canine species, ovaries or oocytes have to be stored to obtain a sufficient number of oocytes at the time of testing. In the present study, the sperm binding capacities of salt-stored oocytes and oocytes from deep frozen ovaries were measured and compared with that of fresh oocytes. Two different procedures for washing the sperm-oocyte complexes (gentle and tough) were used before evaluating the number of bound spermatozoa. The total number of oocytes that bound spermatozoa was significantly lower for both salt-stored and deep frozen oocytes compared with fresh oocytes. Significantly fewer spermatozoa bound to stored oocytes than to fresh oocytes (P 相似文献   

Morphology of spermatozoa in the cauda epididymidis before and after electroejaculation and a comparison with ejaculated spermatozoa in the domestic cat

When 2 ejaculates are collected by electroejaculation from the domestic cat within a period of 10 min the first ejaculate has a higher proportion of abnormal spermatozoa than the second. The reason for this difference is not known for the domestic cat, but in other species long-term epididymal storage results in a higher proportion of abnormal spermatozoa. The aims of this study were to determine the proportions of abnormal spermatozoa in the cauda epididymidis and to ascertain if electroejaculation affects this proportion. Therefore the proportions of spermatozoa in the cauda epididymidis with different morphological abnormalities were compared before and after ejaculation. In addition, the proportion of morphologically abnormal spermatozoa in the epididymis was compared with that in the ejaculate. Nine privately-owned domestic cats were anesthetized, and one testicle was surgically removed. An ejaculate was collected by electroejaculation, after which the remaining testicle was ectomized. There were no significant differences in the proportions of different sperm abnormalities between the cauda epididymidis removed before ejaculation and the one removed after ejaculation. A significantly (P = 0.009) higher proportion of spermatozoa with tail abnormalities was found in the ejaculates compared with the cauda epididymides (11.1 and 1.6%, respectively), while, as expected, there was a lower proportion of spermatozoa with distal droplets in the ejaculates than in the cauda epididymides (35.1 and 75.9%, respectively). This new information contributes to the understanding of the etiology of sperm defects in the domestic cat, and is of importance when evaluating a semen sample in this species.