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  • 1
    Electronic Resource
    Electronic Resource
    The Pharmacokinetics, Distribution and Degradation of Human Recombinant Interleukin 1β in Normal Rats (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 34 (1991), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Based upon in vivo rat experiments it was recently suggested that interleukin I in the circulation may be implicated in the initial events of β-cell destruction leading to insulin-dependent diabetes mellitus (IDDM) in humans. The aim of the present study was to estimate half-lives of distribution and elimination phases (T1/2β) of human recombinant interleukin 1β(rIL-1β), and its tissue distribution and cellular localization by means of mono-labelled, biologically active 125I-rIL-1β. After intravenous (iv.) injection, 125I-rIL-1β was eliminated from the circulation with a T1/2α of 2.9 min and a T1/2β of 41.1 min. The central and peripheral volume of distribution was 20.7 and 19.1 ml/rat, respectively, and the metabolic clearance rate was 16.9 ml/min/kg. The kidney and liver showed the highest accumulation of tracer, and autoradiography demonstrated that 125I-rIL-1β was localized 10 the proximal tubules in the kidney and to the hepatocytes in the liver. Furthermore, grains were localized to the islets of Langerhans in the pancreas. Tracer-bound proteins corresponding to intact 125I-rIL-1β were found in the circulation after i.v., intraperitoneal (i,p.) and subcutaneous (s.c.) injections, as demonstrated by high performance size exclusion chromatography. trichloracetic acid precipitation and SDS PAGE until 5h after tracer injection. Pre-treatment with “cold” rIL-1β enhanced degradation of a subsequent injection of tracer. The route of administration was of importance for the biological effects of rIL-1β as demonstrated by a reduced food intake, increased rectal temperature and blood glucose after s.c. injection of rIL-1β compared with i.p. The present demonstration of intact rIL-1β in the circulation and the islets of Langerhans supports the hypothesis that systemic IL-1β may be involved in the initial 1β-cell destruction leading to IDDM in humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1991.tb01583.x
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  • 2
    Electronic Resource
    Electronic Resource
    Reversed-phase high-performance liquid chromatography of insulin - Resolution and recovery in relation to column geometry and buffer components
    Amsterdam : Elsevier
    Journal of Chromatography A 361 (1986), S. 357-367 
    Details
    ISSN: 0021-9673
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/S0021-9673(01)86926-0
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  • 3
    Electronic Resource
    Electronic Resource
    Separation, isolation and characterization of the four monoiodinated insulin tracers using reversed-phase high-performance liquid chromatography
    Amsterdam : Elsevier
    Journal of Chromatography A 265 (1983), S. 301-309 
    Details
    ISSN: 0021-9673
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/S0021-9673(01)96725-1
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  • 4
    Electronic Resource
    Electronic Resource
    Evidence of changes in renal charge selectivity in patients with Type 1 (insulin-dependent) diabetes mellitus (1986)
    Springer
    Diabetologia 29 (1986), S. 634-639 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; selectivity index ; glycated albumin ; renal albumin clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Altered filtration of macromolecules due to decreased electrical charge of the glomerular basement membrane might be the initial step in the development of albuminuria in patients with Type 1 (insulin-dependent) diabetes mellitus. We therefore investigated the selectivity index, i. e. renal clearance of non-glycated plasma albumin/clearance of glycated plasma albumin in 38 patients with Type 1 diabetes mellitus. The two albumin molecules differed slightly in charge, non-enzymatic glycated albumin being more anionic at physiological pH compared with unmodified plasma albumin. Glycated albumin in plasma and urine was determined by a specific, sensitive and highly reproducible chromatographic procedure. In diabetic patients with normal urinary albumin excretion, the selectivity index was increased threefold compared with that of non-diabetic subjects (2p〈 0.01). A significant correlation (r=0.53, 2p 〈 0.01) between haemoglobin A1c and selectivity index was demonstrated in these patients, indicating a change in charge-dependent renal filtration could possibly be attributed to non-enzymatic glycation of components in the glomerular basement membrane and tubuli. Diabetic patients with increased albumin excretion rate had a significantly lower selectivity index compared with patients with normal albumin excretion (2p 〈 0.01). A significant negative correlation (r=0.85, 2p 〈0.001, exponential curve fit) was seen between urinary albumin excretion and selectivity index in the diabetic patients, indicating that the capability of differentiating between macromolecules of different charges is again lost with increasing urinary albumin excretion. In conclusion, the selectivity index is significantly increased in Type 1 diabetic patients with normal urinary albumin excretion, possibly due to non-enzymatic glycation of structural glomerular proteins. The selectivity index is again reduced with increasing urinary albumin excretion, possibly due to structural changes different from non-enzymatic glycation. This observation is in accordance with the hypothesis that loss of anionic charges due to reduced heparan sulphate content in glomerular basement membranes plays an important role in the early stages of diabetic renal disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00869262
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  • 5
    Electronic Resource
    Electronic Resource
    New approaches to therapy and diagnosis of diabetes (1982)
    Springer
    Diabetologia 22 (1982), S. 61-67 
    Details
    ISSN: 1432-0428
    Keywords: Insulin preparations ; porcine insulin ; bovine insulin ; human insulin ; recombinant DNA ; insulin gene ; polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Conclusion Not only has recombinant DNA added another source of insulin for treatment, but also, and perhaps more important, it has allowed the development of new techniques for studying the structure and function of the B cell at the gene level. We can only hope that this information will bring us closer to the understanding of the disease, so the diabetic patient may benefit from other measures of treatment than the classical replacement therapy introduced by Banting and Best 60 years ago [47].
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00254830
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  • 6
    Electronic Resource
    Electronic Resource
    Rapid changes in chromatographically determined haemoglobin A1c induced by short-term changes in glucose concentration (1980)
    Springer
    Diabetologia 19 (1980), S. 130-136 
    Details
    ISSN: 1432-0428
    Keywords: Haemoglobin A1c ; rapid glycosylation ; chromatography ; glucose ; 2-ketohexose derivatives ; artificial pancreas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Chromatographically determined haemoglobin A1c concentration was measured during short-term (1–24 h) changes in glucose concentration in vitro and in vivo. In vitro at 37 °C the HbA1c concentration increased with glucose concentration and time both in normal and diabetic erythrocytes. In normal erythrocytes incubated in 20–100 mmol/l glucose, the increases in the HbA1c concentration were maximal after 4–6 h and then stable for the next 18–20 h. During the first hour, increases in the HbA1c concentration were linear with time and on average 0.034% HbA1c × h−1 × mmol/l glucose−1. In erythrocytes, after a rapidly produced increase (2h), HbA1c decreased to preincubation concentrations during a further incubation of the erythrocytes in a glucose-free medium at 37 °C for 4–6 h. The mean rate of linear decrease was 0.017% × h−1 × mmol/l glucose−1. After incubation of erythrocytes in 100 mmol/l glucose for 24 h, 1.3% HbA1c remained stable for 6 h in saline. The rapid increase in HbA1c concentration, as determined by chromatography, was not due to stable HbA1c (ketoamine linked glucose) as no increase was found in the HbA1c concentrations determined by the thiobarbiturate method. In juvenile diabetics controlled by an artificial beta-cell, rapid changes of blood glucose concentration (up to 20 mmol/l) resulted in increases in HbA1c concentration of as much as 1.9% within 12 h (mean 1.1%). Rapid in vivo increases in HbA1c concentration were reversible by normalization of the blood glucose concentration. That rapid changes in HbA1c may occur in daily diabetic life was evidenced by differences in HbA1c concentration between blood samples from out-patient diabetics incubated in saline for 16 hours at 4 °C and 37 °C (range of differences 0.2–1.4% HbA1c). The differences correlated to the blood glucose concentration at the time of sampling blood for HbA1c determination. Thus, incubation of blood at a low glucose concentration prior to determination of the glycosylated haemoglobin concentration may overcome interference from rapidly produced HbA1c.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00421859
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  • 7
    Electronic Resource
    Electronic Resource
    Heterogeneity of the haemoglobin-A1c-band in isoelectric focussing (1980)
    Springer
    Diabetologia 19 (1980), S. 465-467 
    Details
    ISSN: 1432-0428
    Keywords: Glycosylated haemoglobin ; isoelectric focussing ; rapid glycosylation ; Schiff-base intermediate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A double HbA1c-band was demonstrated in isoelectric focussing of blood from diabetics with a fasting blood glucose above 11mmol/l. The same band-doubling was also demonstrated after incubation of erythrocytes in glucose/saline solutions. This finding may reflect the presence of the initial condensation product between haemoglobin and glucose, the Schiff-base intermediate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00281827
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  • 8
    Electronic Resource
    Electronic Resource
    Improved metabolic control does not alter the charge-dependent glomerular filtration of albumin in uncomplicated Type 1 (insulin-dependent) diabetes (1988)
    Springer
    Diabetologia 31 (1988), S. 708-710 
    Details
    ISSN: 1432-0428
    Keywords: HbA1c ; Type 1 (insulin-dependent) diabetes mellitus ; glomerular charge ; glycated albumin ; albumin clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The selectivity index, i. e. clearance of non glycated albumin/clearance of glycated albumin was studied in fourteen patients with Type 1 (insulin-dependent) diabetes and normal urinary albumin excretion. The index was increased above one in all patients, and correlated significantly to HbA1c. It was, however, unaffected by 12 weeks of improved metabolic control with a mean decline in HbA1c of 1.9% in seven patients. We conclude that the increased electronegative charge of the glomerular filtration barrier observed in uncomplicated diabetes is related to long term metabolic control but not reversible during twelve weeks of strict metabolic control. This indicates a slow turnover of the components responsible for the increased charge selectivity in uncomplicated diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278756
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