The biomimetic [Cr(3)O(O(2)CCH(2)CH(3))(6)(H(2)O)(3)](+ )decreases plasma insulin, cholesterol, and triglycerides in healthy and type II diabetic rats but not type I diabetic rats.
The in vivo effects of administration of the synthetic, functional biomimetic cation [Cr(3)O(O(2)CCH(2)CH(3))(6)(H(2)O)(3)](+) to healthy and type I and type II diabetic model rats are described. In contrast to current chromium-containing nutrition supplements, which only serve as sources of absorbable chromium, the trinuclear cation has been shown in in vitro assays to interact with the insulin receptor, activating its kinase activity, presumably by trapping the receptor in its active conformation. Thus, treatment of rats with the trinuclear cation would be expected to result in changes in lipid and carbohydrate metabolism related to insulin action. After 24 weeks of intravenous administration (0-20 micro g Cr/kg body mass), the cation results in a concentration-dependent lowering of levels of fasting blood plasma LDL cholesterol, total cholesterol, triglycerides, and insulin and of 2-h plasma insulin and glucose levels after a glucose challenge; these results confirm a previous 12-week study examining the effect of the synthetic cation on healthy rats and are in stark contrast to those of administration of other forms of Cr(III) to rats, which have no effect on these parameters. The cation has little, if any, effect on rats with STZ-induced diabetes (a type I diabetes model). However, Zucker obese rats (a model of the early stages of type II diabetes) after 24 weeks of supplementation (20 micro g/kg) have lower fasting plasma total, HDL, and LDL cholesterol, triglycerides, and insulin levels and lower 2-h plasma insulin levels. The lowering of plasma insulin concentrations with little effect on glucose concentrations suggests that the supplement increases insulin sensitivity.
Department of Chemistry and Coalition for Biomolecular Products, The University of Alabama, Tuscaloosa, AL 35487-0336, USA.
Yanjie
Y
Sun
Buffie J
BJ
Clodfelder
Amanda A
AA
Shute
Turkessa
T
Irvin
John B
JB
Vincent
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001774:Blood Chemical Analysis; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000473:pathology; D004435:Eating / Q000187:drug effects; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008670:Metals / Q000097:blood; D018716:Molecular Mimicry; D009929:Organ Size / Q000187:drug effects; D009942:Organometallic Compounds / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker
D000924:Anticholesteremic Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D008670:Metals; D009942:Organometallic Compounds; C403535:triaquaoxohexakis(propionato)trichromium(III); D002784:Cholesterol