[Indications and possibilities for using an insulin injection device in the treatment of type II diabetes mellitus with intermediate insulin].
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Aged↗
Biomedical subjects
S Zeuzem
Publications and source records attributed to S Zeuzem.
[Asymptomatic giant emphysematous bulla of the lung].
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Adult↗
Biological effects of sulphated insulin in adipocytes and hepatocytes.
The binding affinity of sulphated insulin compared with unmodified, neutral insulin has been reported to be approximately four times lower in human and rat adipocytes but over twenty times lower in rat hepatocytes. In the present study the biological action of sulphated insulin was assessed in rat hepatocytes and human and rat adipocytes. To achieve half-maximal stimulation of fatty acid synthesis in rat hepatocytes about twenty one times higher concentrations of sulphated than neutral insulin were required (15.07 +/- 5.50 vs 0.71 +/- 0.34 nmol/l), this ratio being similar to the ratio of binding affinity in rat hepatocytes. In human adipocytes, half-maximal stimulation of initial rates of glucose uptake was observed at 11.6 +/- 5.1 vs 2.9 +/- 1.3 pmol/l for sulphated and neutral insulin respectively, and half-maximal inhibition of lipolysis at 31.0 +/- 13.5 vs 7.3 +/- 2.5 pmol/l respectively. These data are consistent with the four-fold lower binding affinity of sulphated insulin to human adipocytes. However, in rat adipocytes the biological potency of sulphated insulin was found to be much lower than anticipated from the binding data, half-maximal stimulation of initial rates of glucose uptake being observed at 757 +/- 299 vs 35 +/- 13 pmol/l respectively and half-maximal inhibition of lipolysis at 35.9 +/- 12.1 vs 1.5 +/- 0.5 pmol/l respectively. Thus, in rat adipocytes, approximately 22 times the concentration of sulphated insulin was required to achieve equivalent biological effect. A discrepancy between binding affinity and biological action with respect to sulphated insulin was identified in rat adipocytes but not human adipocytes nor rat hepatocytes suggesting differences in the binding-action linkage in these cells.
Adipose Tissue↗
Insulin secretion, adipocyte insulin binding and insulin sensitivity in thyrotoxicosis.
The pattern of insulin secretion following an oral glucose load and the insulin receptor status and insulin sensitivity of adipocytes have been studied in patients with thyrotoxicosis and in matched controls. Thyrotoxic subjects showed normal basal and peak levels of serum immunoreactive insulin (peak, 69.0 +/- 6.8 vs 54.3 +/- 8.8 mU/l) and serum C-peptide (peak, 1.95 +/- 0.13 vs 1.71 +/- 0.12 nmol/l for thyrotoxic and control subjects, respectively). Peak serum proinsulin was higher in the thyrotoxic group (64.8 +/- 7.3 vs 39.0 +/- 3.7 pmol/l; P less than 0.01). Maximum specific insulin binding to adipocytes was decreased in the thyrotoxic group (1.80 +/- 0.18 vs 2.62 +/- 0.27%; P less than 0.025) and half-maximum displacement of tracer insulin was similar in the two groups, suggesting that reduced receptor number rather than reduced affinity accounted for the difference. However, adipocyte insulin sensitivity was normal as judged by half-maximal stimulation values of 13.9 +/- 3.6 vs 11.4 +/- 2.1 pmol/l, respectively for lipogenesis and 24.3 +/- 2.2 vs 24.6 +/- 3.6 pmol/l, respectively for glucose transport. Hence, thyroid hormone excess appears to affect adipocyte insulin receptor number directly, but change in receptor number is not associated with change in adipocyte insulin sensitivity in hyperthyroidism. The normal insulin secretion together with the failure to demonstrate abnormal insulin sensitivity of one of the major peripheral tissues suggests that disturbed hepatic rather than peripheral insulin responsiveness may be responsible for the glucose intolerance of hyperthyroidism.
Adipose Tissue↗
Assessment of initial hexose uptake in adipocytes using the physiological substrate D-glucose. Particular relevance to human adipocytes.
The characteristics of U-[14C]D-glucose uptake into human and rat adipocytes have been examined. The initial rates of U-[14C]D-glucose uptake were found to be linear during the first 30 s, both basally and with maximum insulin stimulation. Phloretin was shown to be effective in stopping glucose flux for human adipocytes, although rapid separation of cells from medium was found to be necessary for accurate measurement of initial rate of glucose uptake into rat adipocytes. The pH and temperature dependency of U-[14C]D-glucose uptake were found to be similar to those reported for 3-0-methylglucose. The use of U-[14C]D-glucose for assessment of initial rate of glucose uptake into human adipocytes provides results directly relevant to D-glucose metabolism, in addition to being technically less demanding and much less expensive than methods using the non-physiological sugar analogue 3-0-[14C]methylglucose.
Adipose Tissue↗
Differential binding of sulphated insulin to adipocytes and hepatocytes.
The polymerization and precipitation of highly purified insulins which causes major problems in portable infusion systems does not occur with sulphated insulin. To compare the biological behaviour of sulphated insulin with that of a neutral highly purified monocomponent insulin, insulin receptor studies were performed on human and rat adipocytes and rat hepatocytes. Sulphated insulin displayed a lower affinity for binding to both human and rat adipocytes compared with neutral insulin, approximately four times the concentration being required to achieve half-maximal displacement of monoiodoinsulin (p less than 0.05 and 0.01, respectively). A 20-fold higher concentration of sulphated insulin was required for half-maximal displacement from rat hepatocytes (p less than 0.025). However, sulphated insulin bound to liver membranes with an affinity more closely resembling that for adipocytes rather than hepatocytes. Differences in the intracellular processing of the negatively charged insulin could account for the observed lower affinity of binding to hepatocytes.
Adipose Tissue↗
Hepatitis C virus: kinetics and quasispecies evolution during anti-viral therapy.
The balance of virus production and clearance for untreated patients with chronic hepatitis C changes into a decline of viraemia when initiating effective anti-viral treatment. During the first phase of interferon-alpha (IFN-a) therapy, the kinetics of the viral load is characterised by a rapid dose-dependent decline starting after a delay of about eight to nine hours. This early response can be observed for almost all patients treated with IFN-a. After about 24 to 48 hours, the viral decline slows down leading to a second phase with a relatively stable exponential decay. Some non-responding patients show a nearly constant viraemia and some even a rebound throughout this second phase. Kinetic models allow the estimation of rates of viral production and clearance and reveal high turnover rates of hepatitis C virus (HCV) and an in vivo half-life of hepatitis C virions of a few hours, only. Due to the continuous and high replication rate in vivo, the low fidelity of the ribonucleic acid (RNA)-dependent RNA polymerase, and the immune surveillance of the host, HCV exists in an individual patient as a heterogeneous population of related viruses (quasispecies). A high degree of quasispecies variability correlates with a lower response to IFN-a therapy. Changes of the quasispecies population are more pronounced after initiation of treatment with IFN-a or interleukin-12 than during the natural course of disease. Ribavirin, however, has not been found to affect the HCV quasispecies population. Identification of a specific region within an envelope-encoding gene as the most variable region of HCV and as a critical neutralisation domain suggests that viral escape mechanisms are a possible cause for chronification and poses a major challenge for the development of a broadly reactive vaccine against HCV.
Adjuvants, Immunologic↗
Value of the serum levels of the tumor marker TUM2-PK in pancreatic cancer.
The monoclonal antibody pyruvate kinase type tumor M2 (TUM2-PK) has been shown to have a high binding capacity to pancreatic cancer. In present study TUM2-PK serum levels were measured in pancreatic cancer and compared with the reference tumor markers CA19-9, CA50, CA72-4 and CEA. Overall 100 patients were included in this study, 64 patients had a histologically confirmed pancreatic carcinoma, 36 patients gastrointestinal cancer (stomach, colon), 666 healthy volunteers served as controls. Measurements were done by enzymimmunoassay. For the healthy blood donors a cut-off value of 22.5 U/ml was evaluated, which corresponds to 95% specificity. In patients with pancreatic cancer the sensitivities of TUM2-PK, CA19-9, CEA, CA72-4 and CA50 were 71%; 68%, 37%, 49% and 63.4% respectively. Linear regression analysis indicated that there was a positive correlation (r = 0.79). According to the results of our study TUM2-PK has comparable sensitivity but higher specificity than the reference tumor marker CA19-9.
Biomarkers, Tumor↗
Anti-p53 autoantibodies in hepatitis C virus-infected patients.
Mutations in the p53 gene with generation of circulating autoantibodies to p53 protein (anti-p53) have been recently detected in a significant proportion of patients with different malignant diseases. Using ELISA methods we assessed alpha-fetoprotein (AFP) and anti-p53 as serological screening parameters for hepatocellular carcinoma (HCC) in 147 consecutive patients with hepatitis C virus-related chronic hepatitis. Liver cirrhosis was histologically diagnosed in 58 patients (39,5%) and a HCC confirmed in 7 patients (4.8%). Serum AFP levels were raised above 20 ng/ml in 26/147 patients (17.7%) and above 100 ng/ml in 5/147 patients (3.4%). In 6/7 patients with HCC serum AFP was raised above 20 ng/ml, but only in 3/7 cases above 100 ng/ml. Autoantibodies to p53 protein were detected in 3/7 patients with HCC, but in 0/140 patients without HCC (sensitivity 42.9%, specificity 100%). In conclusion, the presence of anti-p53 was specific for malignancy and independent of AFP status. Overall, the sensitivity of serological screening for HCC in patients with hepatitis C virus-related chronic hepatitis was improved by combining AFP measurements (level > 100 ng/ml) with the detection of anti-p53.
Adolescent↗