Insulin soluble

A detailed study by Thiering et al. (102) considered a number of proteins, solvents, and solvent mixtures (Table 3). Insulin was precipitated using SCF CO2 from DMSO, ethyl acetate, methanol, and ethanol. The particle size ranged between 0.05 and 1.8 pm. Insulin precipitated from solvents in which the solubility of insulin was low (ethyl acetate, methanol, ethanol) had a smaller particle size than insulin precipitated from solvents with a higher insulin solubility (DMSO). Polydisperse particles of myoglobin were precipitated from DMSO solutions (mean particle sizes of 0.03 pm and 0.4 pm), whereas monodisperse myoglobin particles were precipitated from a methanol solution (0.05-0.3 pm). 

Figure 2. Isocratic reversed-phase separation of insulin mixtures in four different systems. Conditions Panel A Column, 10 X 0.5 cm SAS—Hypersil (Cl, 5 /tm). Mobile phase, 1% w/v cetrimide in 0.1 M Tris—HCI 10 mM EDTA pH 7.5 methanol, 27 73 (28) temperature, ambient sample, upper trace, bovine insulin soluble formulation lower, porcine insulin neutral formulation following accelerated degradation. Panel B 15 X 0.46 cm ODS Hypersil. Mobile phase, 5 mM tartaric acid—0.1 M ammonium sulphate pH 3 acetonitrile, 73 27 (29) temperature, ambient sample, international reference preparation of insulin for bioassay (established 1956). Panel C 15 X 0.46 cm ODS Hypersil. Mobile phase, 5 mM tartaric acid—0.1 M ammonium sulphate pH 3 acetonitrile 75 25 containing 14 /iM cetrimide (30) temperature, ambient sample, artificial mixture of bovine and porcine insulins and monodesamido insulins. Panel D 25 x 0.46 cm Ultrasphere ODS. Mobile phase, 0.1 M dihydrogen phosphate/phosphoiic acid pH 2 acetonitrile 70 30 temperature, 45°C (30) sample, artificial mixture. Peak identities a, bovine native b, porcine native c bovine A monodesamido d. porcine A monodesamido e. human native f human A monodesamido p, preservative.

Metformin. Metformin [657-24-9] (1,1-dimethylbiguanide), mol wt 129.17, forms crystals from propanol, mp 218—220°C, and is soluble in water and 95% ethanol, but practically insoluble in ether and chloroform. Metformin, an investigational dmg in the United States, does not increase basal or meal-stimulated insulin secretion. It lowers blood glucose levels in hyperglycemic patients with Type II diabetes but has no effect on blood glucose levels in normal subjects. It does not cause hypoglycemia. Successful metformin therapy usually is associated with no or some weight loss. 

Brewers and bakers dried yeasts are used as dietary supplements. They contribute some protein and trace minerals, and some B vitamins, but no vitamin C, vitamin B 2 or fat-soluble vitamins. The glucose tolerance factor (GTE) of yeast, chromium nicotinate, mediates the effect of insulin. It seems to be important for older persons who caimot synthesize GTE from inorganic dietary chromium. The ceU wall fraction of bakers yeast reduces cholesterol levels in rats fed a hypercholesteremic diet. 

Antidiabetic Drugs other than Insulin. Figure 8 Structure of human amylin and its soluble analogue pramlintide. 

The hydrophihc hormones—generally class II and of peptide stmcture—are freely soluble in plasma and do not require transport proteins. Hormones such as insulin, growth hormone, ACTH, and TSH circulate in the free, active form and have very short plasma half-... 

ABNP is soluble in dimethylformamide (DMF) but insoluble directly in aqueous solution. Insulin labeling was done in DMF water at a ratio of 9 1. For molecules not soluble in organic solvent, such as proteins, the trifunctional first may be dissolved in DMF and a small aliquot added to an aqueous reaction medium. The nitrophenyl ester reactive group can be coupled to amine groups at alkaline pFI (7-9) and in buffers containing no extraneous amines (avoid Tris). Unfortunately, ABNP is not commercially available at the time of this writing. 

The concentration of insulin present in soluble insulin preparations (i.e. fast-acting insulins), is much higher (approximately 1 x KT2 3 mol I ). At this concentration, the soluble insulin exists as a mixture of monomer, dimer, tetramer and zinc-insulin hexamer. These insulin complexes have to dissociate in order to be absorbed from the injection site into the blood, which slows down the onset of hormone action. 

In order to prolong the duration of insulin action, soluble insulin may be formulated to generate insulin suspensions. This is generally achieved in one of two ways ... 

A number of studies have also focused upon the generation of longer-acting insulin analogues. The currently used Zn-insulin suspensions, or protamine-Zn-insulin suspensions, generally display a plasma half-life of 20-25 h. Selected amino acid substitutions have generated insulins which, even in soluble form, exhibit plasma half-lives of up to 35 h. 

It was discovered nearly 20 years ago that V(V) as vanadate and V(IV) as vanadyl can mimic some of the effects of insulin (stimulate glucose uptake and oxidation and glycogen synthesis) (512, 513). Vanadate is an effective insulin mimetic in the diabetic rat (514), but has proved to be too toxic for human use. Vanadyl, as VOS04, is also unsuitable because high doses are needed on account of its poor oral absorption. Vanadium complexes with organic ligands have proved to be less toxic and can have improved aqueous solubility and lipophil-icity. 

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