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S Kang

Publications and source records attributed to S Kang.

At least 217 records · Page 12Linked to original sources
PubMed1991

Absorption kinetics and action profiles of subcutaneously administered insulin analogues (AspB9GluB27, AspB10, AspB28) in healthy subjects.

OBJECTIVE: The subcutaneous absorption and resulting changes in plasma insulin or analogue, glucose, C-peptide, and blood intermediary metabolite concentrations after subcutaneous bolus injection of three soluble human insulin analogues (AspB9GluB27, monomeric; AspB28, mixture of monomers and dimers; and AspB10, dimeric) and soluble human insulin were evaluated. RESEARCH DESIGN AND METHODS: Fasting healthy male volunteers (n = 7) were studied on five occasions 1 wk apart randomly receiving 0.6 nmol.kg-1 s.c. 125I-labeled AspB10 or soluble human insulin (Novolin R, Novo, Copenhagen); 1st study and 0.6 nmol.kg-1 s.c. 125I-labeled AspB28, AspB9GluB27 or soluble human insulin (2nd study). Residual radioactivity at the injection site was measured over 8 h with frequent venous sampling for plasma immunoreactive insulin or analogue, glucose, C-peptide, and blood intermediary metabolite concentrations. RESULTS: The three analogues were absorbed 2-3 times faster than human insulin. The mean +/- SE time to 50% residual radioactivity was 94 +/- 6 min for AspB10 compared with 184 +/- 10 min for human insulin (P less than 0.001), 83 +/- 8 min for AspB28 (P less than 0.005), and 63 +/- 9 min for AspB9GluB27 (P less than 0.001) compared with 182 +/- 21 min for human insulin. delta Peak plasma insulin analogue levels were significantly higher after each analogue than after human insulin (P less than 0.005). With all three analogues, the mean hypoglycemic nadir occurred earlier at 61-65 min postinjection compared with 201-210 min for the reference human insulins (P less than 0.005). The magnitude of the hypoglycemic nadir was greater after AspB9GluB27 (P less than 0.05) and AspB28 (P less than 0.001) compared with human insulin. There was a significantly faster onset and offset of responses in C-peptide and intermediary metabolite levels after the analogues than after human insulin (P less than 0.05). CONCLUSIONS: The rapid absorption and biological actions of these analogues offer potential therapeutic advantages over the current short-acting neutral soluble insulins.

3-Hydroxybutyric Acid↗
PubMed1991

Subcutaneous insulin absorption explained by insulin's physicochemical properties. Evidence from absorption studies of soluble human insulin and insulin analogues in humans.

OBJECTIVE: To study the influence of molecular aggregation on rates of subcutaneous insulin absorption and to attempt to elucidate the mechanism of absorption of conventional soluble human insulin in humans. RESEARCH DESIGN AND METHODS: Seven healthy male volunteers aged 22-43 yr and not receiving any drugs comprised the study. This study consisted of a single-blind randomized comparison of equimolar dosages of 125I-labeled forms of soluble hexameric 2 Zn2+ human insulin and human insulin analogues with differing association states at pharmaceutical concentrations (AspB10, dimeric; AspB28, mixture of monomers and dimers; AspB9, GluB27, monomeric). After an overnight fast and a basal period of 1 h, 0.6 nmol/kg of either 125I-labeled human soluble insulin (Actrapid HM U-100) or 125I-labeled analogue was injected subcutaneously on 4 separate days 1 wk apart. Absorption was assessed by measurement of residual radioactivity at the injection site by external gamma-counting. RESULTS: The mean +/- SE initial fractional disappearance rates for the four preparations were 20.7 +/- 1.9 (hexameric soluble human insulin), 44.4 +/- 2.5 (dimeric analogue AspB10), 50.6 +/- 3.9 (analogue AspB28), and 67.4 +/- 7.4%/h (monomeric analogue AspB9, GluB27). Absorption of the dimeric analogue was significantly faster than that of hexameric human insulin (P less than 0.001); absorption of monomeric insulin analogue AspB9, GluB27 was significantly faster than that of dimeric analogue AspB10 (P less than 0.01). There was an inverse linear correlation between association state and the initial fractional disappearance rates (r = -0.98, P less than 0.02). Analysis of the disappearance data on a log linear scale showed that only the monomeric analogue had a monoexponential course throughout. Two phases in the rates of absorption were identified for the dimer and three for hexameric human insulin. The fractional disappearance rates (%/h) calculated by log linear regression analysis were monomer 73.3 +/- 6.8; dimer 44.4 +/- 2.5 from 0 to 2 h and 68.9 +/- 3.5 from 2.5 h onward; and hexameric insulin 20.7 +/- 1.9 from 0 to 2 h, 45.6 +/- 5.0 from 2.5 to 5 h, and 70.6 +/- 6.3 from 5 h onward. CONCLUSIONS: Association state is a major determinant of rates of absorption of insulin and insulin analogues. The lag phase and the subsequent increasing rate of subcutaneous soluble insulin absorption can be explained by the associated state of native insulin in pharmaceutical formulation and its progressive dissociation into smaller units during the absorption process.

Absorption↗
PubMed1991

Comparison of subcutaneous soluble human insulin and insulin analogues (AspB9, GluB27; AspB10; AspB28) on meal-related plasma glucose excursions in type I diabetic subjects.

OBJECTIVE: To compare postprandial glucose excursions and plasma free insulin-analogue levels after subcutaneous injection of three novel human insulin analogues (AspB10; AspB9, GluB27; and AspB28) with those after injection of soluble human insulin (Actrapid HM U-100). RESEARCH DESIGN AND METHODS: Six male subjects with insulin-dependent diabetes, at least 1 wk apart and after an overnight fast and basal insulin infusion, received 72 nmol (approximately 12 U) s.c. of soluble human insulin 30 min before, or 72 nmol of each of the three analogues immediately before, a standard 500-kcal meal. RESULTS: Mean basal glucoses were similar on the 4 study days. Compared to human insulin (6.3 +/- 0.8 mM), mean +/- SE peak incremental glucose rises were similar after analogues AspB10 (5.4 +/- 0.8 mM) and AspB9, GluB27 (5.4 +/- 0.7 mM) and significantly lower after analogue AspB28 (3.6 +/- 1.2 mM, P less than 0.02). Relative to soluble human insulin (100% +/- SE21), incremental areas under the glucose curve between 0 and 240 min were 79% +/- 34 (AspB10, NS), 70% +/- 29 (AspB9, GluB27, NS), and 43% +/- 23 (AspB28, P less than 0.02). Basal plasma free insulin levels were similar on the 4 study days. Plasma free insulin-analogue levels rose rapidly to peak 30 min after injection at 308 +/- 44 pM (AspB10); 1231 +/- 190 pM (AspB9, GluB27) and 414 +/- 42 pM (AspB28) and were significantly higher than corresponding (i.e., 30 min postmeal) plasma free insulin levels of 157 +/- 15 pM (P less than 0.02 in each case). CONCLUSIONS: Plasma profiles of the insulin analogues were more physiological than that of human insulin after subcutaneous injection. All three analogues given immediately before the meal are at least as effective as soluble human insulin given 30 min earlier. These analogues are promising potential candidates for short-acting insulins of the future.

Adult↗
PubMed1991

[The qualitative and quantitative analyses of protein with a novel fluorescence agent (EPQS) by fluorescent scanning on solid substrate].

We synthesized a new fluorescence agent, EPQS, which could be soluble in water and was stable in the analytical process. It was characteristic of good fluorescence parameters. Human serum albumin (HSA) was marked with EPQS and purified by the paper electrophoresis dialysis. We determined the fluorescent spectra and excitation spectra of the marked HSA, or EPQS on the cellulose acetate paper by RF-510 fluorescence spectrophotometer-thin-layer chromatoscanner. The former lambda ex = 370nm lambda em = 470nm; the latter lambda ex = 382nm lambda em = 476 nm. Then we touched different quantity of EPQS-HSA upon the cellulose acetate. The fluorescent scanning on the paper disclosed that the relationship between the quantity adopted and the fluorescence intensity is linear. These showed that the protein could be quickly determined qualitatively and quantitatively by this simple method, and EPQS was useful.

Chromatography, Thin Layer↗
PubMed1990

Comparison of insulin analogue B9AspB27Glu and soluble human insulin in insulin-treated diabetes.

Postprandial plasma glucose excursions and plasma levels of free insulin after subcutaneous bolus injection of a rapidly absorbed monomeric insulin analogue (B9AspB27Glu) or soluble human insulin ('Actrapid HM' U100) were studied in six insulin-treated diabetic subjects. 10 U actrapid or an equimolar amount of the analogue were injected, in random order with an interval of 1 week, immediately before a 500 kcal test meal. Basal insulin levels were similar on the 2 study days (mean 74.1 [SE 5.1] pmol/l, actrapid; 79.7 [13.0] pmol/l, analogue). After injection of actrapid plasma free insulin levels rose slowly, reaching a plateau by 105 min at 222 (19) pmol/l. Injection of the analogue resulted in a rapid early peak at 30 min (798 [112] pmol/l), and levels were significantly higher than those after actrapid between 15 and 210 min. The more physiological plasma insulin levels achieved with the analogue were accompanied by a substantial reduction in postprandial plasma glucose excursions; the integrated area under the incremental plasma glucose curve was 45% lower after the analogue than after actrapid.

Adult↗
PubMed1990

Molecular analysis of nuc-1+, a gene controlling phosphorus acquisition in Neurospora crassa.

In response to phosphorus starvation, Neurospora crassa makes several enzymes that are undetectable or barely detectable in phosphate-sufficient cultures. The nuc-1+ gene, whose product regulates the synthesis of these enzymes, was cloned and sequenced. The nuc-1+ gene encodes a protein of 824 amino acids with a predicted molecular weight of 87,429. The amino acid sequence shows homology with two yeast proteins whose functions are analogous to that of the NUC-1 protein. Two nuc-1+ transcripts of 3.2 and 3.0 kilobases were detected; they were present in similar amounts during growth at low or high phosphate concentrations. The nuc-2+ gene encodes a product normally required for NUC-1 function, and yet a nuc-2 mutation can be complemented by overexpression of the nuc-1+ gene. This implies physical interactions between NUC-1 protein and the negative regulatory factor(s) PREG and/or PGOV. Analysis of nuc-2 and nuc-1; nuc-2 strains transformed by the nuc-1+ gene suggests that phosphate directly affects the level or activity of the negative regulatory factor(s) controlling phosphorus acquisition.

Alkaline Phosphatase↗
PubMed1990

Monomeric insulins and their experimental and clinical implications.

Due to the inherent pharmacokinetic properties of available insulins, normoglycemia is rarely, if ever, achieved in insulin-dependent diabetic patients without compromising their quality of life. Subcutaneous insulin absorption is influenced by many factors, among which the associated state of insulin (hexameric) in pharmaceutical formulation may be of importance. This review describes the development of a series of human insulin analogues with reduced tendency to self-association that, because of more rapid absorption, are better suited to meal-related therapy. DNA technology has made it possible to prepare insulins that remain dimeric or even monomeric at high concentration by introducing one or a few amino acid substitutions into human insulin. These analogues were characterized and used for elucidating the mechanisms involved in subcutaneous absorption and were investigated in preliminary clinical studies. Their relative receptor binding and in vitro potency (free-fat cell assay), ranging from 0.05 to 600% relative to human insulin, were strongly correlated (r = 0.97). In vivo, most of the analogues exhibited approximately 100% activity, explainable by a dominating receptor-mediated clearance. This was confirmed by clamp studies in which correlation between receptor binding and clearance was observed. Thus, an analogue with reduced binding and clearance gives higher circulating concentrations, counterbalancing the reduced potency at the cellular level. Absorption studies in pigs revealed a strong inverse correlation (r = 0.96) between the rate of subcutaneous absorption and the mean association state of the insulin analogues. These studies also demonstrated that monomeric insulins were absorbed three times faster than human insulin. In healthy subjects, rates of disappearance from subcutis were two to three times faster for dimeric and monomeric analogues than for human insulin. Concomitantly, a more rapid rise in plasma insulin concentration and an earlier hypoglycemic response with the analogues were observed. The monomeric insulin had no lag phase and followed a monoexponential course throughout the absorption process. In contrast, two phases in rate of absorption were identified for the dimer and three for the normal hexameric human insulin. The initial lag phase and the subsequent accelerated absorption of soluble insulin can now be explained by the associated state of native insulin in pharmaceutical formulation and its progressive dissociation into smaller units during the absorption process. In the light of these results, the effects of insulin concentration, injected volume, temperature, and massage on the absorption process are now also understood.(ABSTRACT TRUNCATED AT 400 WORDS)

Diabetes Mellitus, Type 1↗
PubMed1988

Recombinant DNA derived monomeric insulin analogue: comparison with soluble human insulin in normal subjects.

OBJECTIVE: To compare the rate of absorption from subcutaneous tissue and the resulting hypoglycaemic effect of iodine-125 labelled soluble human insulin and a monomeric insulin analogue derived by recombinant DNA technology. DESIGN: Single blind randomised comparison of equimolar doses of 125I labelled soluble human insulin and insulin analogue. SETTING: Study in normal people at a diabetes research unit and a university department of medical physics. SUBJECTS: Seven healthy male volunteers aged 20-39 not receiving any other drugs. INTERVENTIONS: After an overnight fast and a basal period of one hour two doses (0.05 and 0.1 U/kg) of 125I labelled soluble human insulin and insulin analogue were injected subcutaneously into the anterior abdominal wall on four separate days. END POINT: To find a fast acting insulin for meal related requirements in insulin dependent diabetics. MEASUREMENTS and main results--Residual radioactivity at the injection site was measured continuously for the first two hours after injection of the 125I labelled preparations and thereafter for five minutes simultaneously with blood sampling. Frequent venous blood samples were obtained over six hours for determination of plasma immunoreactive insulin, insulin analogue, glucose, and glucagon values. Time to 50% of initial radioactivity at the injection site for the insulin analogue compared with soluble insulin was 61 v 135 minutes (p less than 0.05) with 0.05 U/kg and 67 v 145 minutes (p less than 0.001) with 0.1 U/kg. Concentrations in plasma increased faster after the insulin analogue compared with soluble insulin, resulting in higher plasma concentrations between 10 and 150 minutes (0.001 less than p less than 0.05) after 0.05 U/kg and between 40 and 360 minutes (0.001 less than p less than 0.05) after 0.1 U/kg. The hypoglycaemic response to insulin analogue was a plasma glucose nadir at 60 minutes with both doses compared with 90 and 120 minutes with soluble insulin at 0.5 and 0.1 U/kg respectively. The response of glucagon substantiated the earlier and more dramatic hypoglycaemic effect with the insulin analogue. CONCLUSIONS: The much faster absorption from subcutaneous tissue of the disubstituted monomeric insulin analogue compared with soluble insulin suggests that the analogue may be a potential candidate for rapid insulin delivery after subcutaneous bolus injection.

Absorption↗
PubMed1988

Purification of human brain tissue factor.

Tissue factor (thromboplastin or Factor III), a glycoprotein cofactor, is required for Factor VII to express its catalytic activity, thereby initiating the extrinsic as well as intrinsic pathway of blood coagulation. Human brain tissue factor was purified 2,500-fold to 98% homogeneity from 2% Triton X-100 extraction of acetone dried brain powder with an overall yield of 36%. The method was based upon affinity chromatography utilizing the high affinity binding of tissue factor to Factor VII noncovalently complexed to immobilized anti-Factor VII-agarose beads. The apparent molecular weight of the purified tissue factor is 45,000 as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and its isoelectric point is 4.8-5.1 by column chromatofocussing and flat bed agarose isoelectric focussing.

Brain Chemistry↗
PubMed1988

A streptokinase dependent plasma factor (SKDF) induces leucocyte tissue factor activity.

Various inducers endow human leucocytes with a procoagulant activity of tissue factor type. We have observed a novel plasma factor which in combination with streptokinase induces powerful leucocyte procoagulant activity. This streptokinase dependent factor (SKDF) is present in normal plasma or serum albeit quantitatively different in individual donors. The generation of tissue factor activity as a function of streptokinase-plasma complex shows a specific and saturable sigmoidal dose-response curve. The Hill plot shows a straight line with Hill coefficient, H = 2.2, suggesting a strong positive cooperativity for the binding of this streptokinase-plasma complex to the leucocyte surface receptor for the signal transduction leading to the biosynthesis of tissue factor apoprotein. It also suggests that the leucocyte surface receptor for streptokinase-plasma complex differs from that for endotoxin lipopolysaccharides. SKDF is of apparent high molecular weight. It does not appear to be an antibody to streptokinase since its level does not correlate with the level of antibodies to streptokinase, and it does not correlate with the antistreptolysin titre. Furthermore, SKDF does not bind to protein A. It has a narrow pH range of stability, and is destroyed at 56 degrees C, or at freeze-drying, Urokinase, another plasminogen activator, or plasmin were unable to activate SKDF to induce the leucocyte procoagulant activity. SKDF may play a role in thrombolytic therapy.

Antibodies↗
PubMed1987

Glucose and insulin responses are improved in patients with psoriasis during therapy with etretinate.

Since lipemia is commonly induced by retinoid therapy, we investigated the effects of etretinate administration on glucose metabolism by obtaining five-hour oral glucose tolerance tests in 23 patients before and after 20 weeks of etretinate therapy for psoriasis. Compared with pretreatment values, peak and aggregate levels for serum glucose and aggregate levels for serum insulin were significantly lower during therapy. The changes were not associated with obesity, weight loss during treatment, or pretherapy glucose tolerance or insulin secretion level. Of 11 patients with impaired or diabetic glucose tolerance prior to therapy, eight patients had improved glucose tolerance after 20 weeks of etretinate treatment. Despite inducing hypertriglyceridemia in most patients, etretinate therapy is associated with a reduction in glucose levels in response to a glucose load.

Adult↗
PubMed1986

Topical application of nonsteroidal anti-inflammatory drugs prevents vehicle-induced improvement of psoriasis.

In a double-blind fashion, we compared the effect of topical application of 1% indomethacin cream or 1% meclofenamate cream with the effect of vehicle therapy alone in thirty patients with psoriasis. After 4 weeks' treatment of bilaterally symmetric psoriatic plaques, the indomethacin-treated sides were worse than the vehicle-treated sides in fourteen of twenty patients (p less than 0.01); the meclofenamate-treated sides were worse than the vehicle-treated sides in seven of ten patients (p less than 0.05). We suspect that the nonsteroidal anti-inflammatory drugs contributed to the maintenance of our patients' psoriasis by altering the arachidonic acid transformation cascade.

Administration, Topical↗