Serine protease hepsin (EC 188.8.131.52) (Transmembrane protease serine 1) [Contains: Serine protease hepsin non-catalytic chain; Serine protease hepsin catalytic chain] [TMPRSS1]
With aging, there is a decrease in parasympathetic nervous activity. Since the hepatic parasympathetic nerves (HPNs) are essential to the disposal of nutrients, through the hepatic insulin sensitizing substance (HISS), we tested the hypothesis that aging leads to a lowering of postprandial glucose disposal by a decrease of the HISS-dependent component of insulin action. Insulin sensitivity was quantified in fed or fasted, male and female Wistar rats (from 6 to 52 weeks), using a euglycemic clamp. The HISS-dependent component was quantified by administration of the muscarinic antagonist atropine. Total insulin action decreased gradually up to 52 weeks of age: The HISS-independent component of insulin action decreased until 9 weeks of age and remained unchanged thereafter; the HISS-dependent component decreased from 9 weeks of age throughout aging. The continuous decrease of HISS action, uncovered by blocking the HPN, is the key phenomenon for the gradual decrease of insulin sensitivity with aging.
- Insulin Resistance
- Parasympathetic Nervous System
- Rats, Wistar
- Sex Factors
The British Artificial Nutrition Survey 2001 recorded 507 home parenteral nutrition (HPN) patients (Crohn's disease 31.5%, vascular disease 19.7%, cancer 6.9%). Parenteral nutrition was administered via tunnelled central line (92%) and supplied by a commercial homecare company in 89% of cases. The majority of HPN patients live at home (95.5%) with an independent life (74%), normal activity (59.2%) and 92% survive 1 year. However, there is good evidence that the geographical distribution of HPN patients is uneven (prevalence no patients to thirty-six patients per million of the population) suggesting inequity of access. Patients are increasingly concerned about the distances travelled to main centres and variable standards of more local support. Funding issues continue to cause difficulties as commissioning of health care transfers from Health Authorities to Primary Care Trusts. The two nationally-funded intestinal failure units provide HPN services to 220 HPN patients. HPN-related readmissions have displaced those awaiting admission for intestinal failure treatment, for which the waiting list mortality in one unit has risen to 14%. The government has now recognised HPN as a specialised service distinct from intestinal failure and that existing medium-sized HPN units should be encouraged to take on HPN patients from intestinal failure units and smaller units. In Scotland a Managed Clinical HPN Network supported by the Scottish administration now cares for seventy-two patients under common protocols. The challenge for the future is how to provide high-quality care to all who need it in the rest of the UK.
- Aged, 80 and over
- Health Services Accessibility
- Home Care Services
- Intestinal Diseases
- Middle Aged
- Nutrition Surveys
- Parenteral Nutrition, Home
- Quality of Health Care
- United Kingdom
Administration of 2-acetylaminofluorene to rats for 12 weeks induces hyperplastic nodules (HPNs) and later well-differentiated hepatocellular carcinomas (HCCs) in the liver. Total cellular proteins from normal liver, HPN, and HCC were analyzed by two-dimensional gel electrophoresis with a high resolution. Several hundred polypeptides were well resolved as seen by Coomassie blue staining, forming a reproducible and characteristic pattern for each tissue. The polypeptide patterns were very similar among normal liver, HPN, and HCC. Especially the proteins of HPN and HCC were almost indistinguishable. These neoplastic lesions, however, were clearly different from control liver in that a new spot p35-6.6 (designated by molecular weight X 10(-3) and pl) appeared, and five polypeptides, p57-6.9, p57-6.7, p26-6.9, p26-6.6, p26-6.4, increased dramatically in amount as compared with normal liver. These last three spots were found to be a new type of glutathione S-transferase as judged from the specific binding to the antibody. The same changes in polypeptide pattern were found in HCCs induced by other chemical carcinogens, diethylnitrosamine and 3'-methyl-4-dimethylaminoazobenzene, but not in regenerating and neonatal livers. Fetal liver showed a rather different pattern than adult liver, but only p26-6.6 was increased among the spots characteristic of HPN and HCC. Protein phosphorylation was also examined for these cells by incubating tissue slices with 32PO4. After alkali treatment of the gels to eliminate serines phosphorylation, several dozens of phosphoproteins were clearly detected. The patterns of the labeled spots were again very similar among control liver, HPN, and HCC. Only the intensity of a spot designated p57-6.6 increased markedly in both HPN and HCC. This spot was further resolved by an expanded pH gradient into four distinct spots, the major one of which contained phosphothreonine. Similar changes in phosphorylation were noted in hepatomas induced by diethylnitrosamine and 3'-methyl-4-dimethylaminoazobenzene but not in regenerating, fetal, and neonatal livers. These changes are discussed in terms of gene expression relevant to malignant transformation of hepatic cells.
- Cell Transformation, Neoplastic
- Liver Neoplasms, Experimental
- Liver Regeneration
- Molecular Weight
- Neoplasm Proteins
- Precancerous Conditions
- Rats, Inbred Strains