Search PubMed⌕ Search

Biomedical subjects

L Keller

Publications and source records attributed to L Keller.

At least 91 records · Page 5Linked to original sources
PubMed1978

C-peptide secretion during the remission phase of juvenile diabetes.

C-peptide secretion was studied in eight juvenile diabetics during the remission phase of the disease. The release of C-peptide was measured after a (1) normal intravenous glucose tolerance test, (2) a double glucose tolerance test, (3) an arginine infusion, and (4) after an intravenous glucose tolerance test followed by an arginine infusion. Under all conditions the intravenous glucose load had only a minimal effect on the secretion of C-peptide, while arginine alone or after the intravenous glucose tolerance test stimulated the release of the peptide in all patients. Pretreatment with glucose did not augment the effect of arginine on C-peptide release. The results indicate that during the remission phase of juvenile-onset diabetes the endocrine pancreas does not recognize glucose as and appropriate signal for C-peptide release and cannot transform the amplifying effect of glucose into a higher hormonal secretion rate.

Adolescent↗
PubMed1976

Human C-peptide. Part I: Radioimmunoassay.

Synthetic human C-peptide bearing a Tyrosine group at its amino end is labelled with 125iodine using chloramin T or hydrogen peroxide and lactoperoxidase. The results are compared applying both methods. Antiserum to synthetic human C-peptide (without Tyrosine) which was partially compared to rabbit albumin, is raised in guinea pigs and goats. Goats show to be superior to guinea pigs concerning antibody production. The so-called "hook effect" phenomenon is observed in setting up the standard curves for the radioimmunoassay. Monotonically decreasing standard curves are obtained on dilution of antiserum with a high antibody titer which was produced by repeated immunization in goats. Free C-peptide and C-peptide bound to antiserum are separated with the anxion exchange resin Amberlite. Using this separation technique we excluded unspecific binding of labelled C-peptide to protein fractions in serum of diabetics. The sensitivity of our radioimmunoassay is approx. 0.3 ng C-peptide/ml serum. Intra- and interassay variability are below 10%. Human proinsulin is the only substance found to crossreact with the antiserum.

Animals↗
PubMed1976

Human C-peptide. Part II: Clinical studies.

Human C-peptide is determined by radioimmunoassay. On gel filtration of serum from a healthy subject and from a patient with islet cell carcinoma, C-peptide (MW 3025) appears ahead of insulin (MW 5808) and shows much higher molar concentrations than the hormone. Human proinsulin cross-reacts with our antiserum to synthetic human C-peptide. On direct determination of immunomeasurable C-peptide (IMCP) in fasting serum of 25 healthy subjects we find an average of 1.8 (+/- 0.4) ng/ml, corresponding to 60.4 X 10(-11) Mol/l. The molar concentration is about five-fold as compared to IMI (immuno-measurable insulin). IMCP and IMI patterns are not identical on stimulation of beta-cell secretion in healthy subjects by i.v. glucose or glucose-glibenclamide. This is probably due to differences in peripheral metabolism of both compounds. We conclude from our results that C-peptide determined in peripheral venous serum is a better indicator of beta-cell secretion than is insulin. Among 26 insulin-treated juvenile diabetics 15 show not measurable and 11 subnormal IMCP levels in fasting serum. No rise in IMCP is found 1-2 h following breakfast. Four juvenile patients receiving no insulin in a phase of total diabetes remission have normal or raised fasting IMCP concentrations. Only 2 out of 24 adult diabetics (16 treated with insulin and 8 with tablets) show non-measurable fasting IMCP concentrations, in another 4 patients values are below and in the remaining 18 cases above 1 ng/ml serum. Stimulation of beta-cell secretion through glucose-glibenclamide is more or less impaired in all adult diabetics compared to the healthy subjects.

C-Peptide↗
PubMed1976

High-molecular IRI (big, big insulin) in islet cell adenoma.

In agreement with data previously reported (Yalow and Berson 1973), after gel filtration of acid-ethanol extracts of islet cell adenomas (performed in 3 M acetic acid) 1.4% to 1.8% of total immunoreactive insulin (IRI) eluted ahead of proinsulin. The high-molecular IRI (HM-IRI) was, however, found to be heterogenous in size and consisted of at least three components, the major one having an estimated molecular weight of about 50,000. Under certain conditions, HM-IRI was partially dissociated into proinsulin- and insulin-like components. We conclude that HM-IRI does not represent a precursor of proinsulin and insulin, but probably a self-association product of the peptides or an association of insulin and proinsulin to other proteins extracted from tumor tissue.

Adenoma↗
PubMed1975

Chromatographic heterogeneity of insulin extracted from insulomas.

On gel filtration of acid-ethanol extracts from three pancreatic beta-cell adenomas 1.4% to 1.8% of total immunomeasurable insulin (IMI) eluted ahead of proinsulin. This high molecular IMI was resolved into three components. The presence of urea in the dilute acetic acid solutions of extracted tumor tissue did not influence the pattern of gel filtration. High molecular IMI dissolved in dilute acetic acid showed to be stable if immediately rechromatographed, but a partial dissociation to insulinlike and proinsulinlike components (ILC and PLC) was found if rechromatography was performed after 48 h of incubation. Mainly ILC and PLC were found on rechromatography provided high molecular IMI was dissolved and incubated briefly in 0.04M phosphate buffer, pH 7.4. It proved improbable that the proteolytic action of some protein being extracted with the hormones caused a splitting of high molecular IMI at pH 7.4. We conclude from our findings that the components of high molecular IMI are not precursors of proinsulin and insulin but are either self-associated products of the hormones or associations of insulin and proinsulin to other proteins extracted from insuloma tissue.

Adenoma, Islet Cell↗