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K K Schmiegel

Publications and source records attributed to K K Schmiegel.

4 recordsLinked to original sources
PubMed1997

Competitive particle concentration fluorescence immunoassays for measuring anti-diabetic drug levels in mouse plasma.

Two competitive particle concentration fluorescence immunoassays were developed to measure blood levels of analogs of anti-diabetic drugs being tested in diabetic mice. Ligands that contained the active pharmacophores were conjugated to PPD for immunization and to beta-phycoerythrin for use as a tracer in the immunoassays. Approximately 90% of 262 compounds assayed were detectable at less than 120 nM in plasma which was well below the estimated therapeutic level of 1 microM for lowering blood glucose. These data were used to define the bioavailability of test compounds and assist in decisions of constructing active analogs. Of additional interest, we noted crossreactivity of one monoclonal antibody for 3 different compound classes that are all known to bind with varying affinities to peroxisome proliferator-activated receptors.

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PubMed1997

Monoclonal antibodies as surrogate receptors in a high throughput screen for compounds that enhance insulin sensitivity.

Monoclonal antibodies (MoAbs) were made to a known insulin sensitivity enhancer (ISE) compound, CS-045. The MoAbs were characterized with respect to binding other known thiazolidinedione ISE compounds using a CS-045 labeled with b-phycoerythrin in a competitive particle concentration fluorescence immunoassay (PCFIA). By comparing the rank order of IC50 values for each compound to its respective potency as an ISE, one MoAb (13E3) was selected for further characterization. This MoAb was also used as a surrogate receptor in a high throughput screen to identify novel compounds that compete for binding to CS-045. Some of the hits were found to have efficacy in reducing blood glucose. Subsequently, another group reported that several compounds with the core thiazolidinedione structure of the ISE compounds bound with high affinity to peroxisome proliferator-activating receptors (PPAR). Therefore, we used the MoAb assay to test these and other compounds that are known to bind to PPARgamma and noted crossreactivity with some of the compounds.

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PubMedDate not supplied

Compound M & B 39890A [N-(3-imidazol-1-ylpropyl)- 2-(3-trifluoromethylbenezensulphonamido)-benzamide hydrochloride], a glucagon and insulin secretion inhibitor, improves insulin sensitivity in viable yellow obese-diabetic mice.

Compound M & B 39890A [N-(3-imidazol-1-ylpropyl)-2- (3-trifluoromethylbenzenesulphonamido)benzamide hydrochloride] had no effect on cellular cAMP and cGMP levels but significantly inhibited insulin and glucagon secretion from freshly isolated normal rat islets stimulated with 10 mM glucose and 20 mM arginine. Daily gavage of the compound for three days lowered the elevated blood glucose and plasma insulin levels in fed, male viable yellow obese-diabetic mice; the minimum effective dose was 25 mg/kg. However, M & B 39890A did not affect the blood glucose level of fasted diabetic mice. In addition, it had no effect on blood glucose levels of normal mice and streptozotocin-diabetic rats. M & B 39890A, fed in the diet at the concentration of 1 mg/g for 42 days, reversed the hyperglycemia of the fed diabetic mice without causing tachyphylaxis and improved the sensitivity to exogenous insulin as demonstrated by the lowering of blood glucose. When M & B 39890A was fed to young male mice destined to become diabetic, the development of hyperglycemia was prevented. Thus, M & B 39890A represents a new class of pharmacological agents that may prove to be effective for the chronic treatment of type II diabetics without the risk of hypoglycemia.

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