Insulin-like Action of Chromate on Glucose Transport in Isolated Rat Adipocytes

Abstract

ABSTRACT-The effects of chromium compounds on 3-O-methylglucose (3-0-MG) transport were studied in isolated rat adipocytes. Sodium chromate significantly stimulated 3-0-MG uptake into adipocytes in a dose-dependent manner without altering the equilibrium space of 3-0-MG in adipocytes. The stimulatory effect reached the maximum at 300 pM, and the effect was 60 -70070 of the maximal insulin effect that was obtained with 20 nM insulin. The chromate concentration achieving a half-maximal effect was estimated at 50 pM. The effect of the combination of 1 mM chromate and 20 nM insulin was equipotent to that of 20 nM insulin alone, which showed that these two effects were not additive. The stimulatory effects of 1 mM chromate and 20 nM insulin were entirely abolished in adipocytes deprived of ATP, which indicated that these effects were completely ATP-dependent.Judging from experiments using various chromium compounds, Cr042-was responsible for the insulinomimetic action. These results indicate that the action of Cr042-is exerted through a mechanism analogous to that of insulin action, and that Cr042-is a novel and useful tool for studying issues involved in insulin actions.

Chromium picolinate positively influences the glucose transporter system via affecting cholesterol homeostasis in adipocytes cultured under hyperglycemic diabetic conditions

“…The relative enhancing effect of metformin was higher in cells incubated in 25 mM glucose rather than in 5 mM glucose, consistent with its selective action in hyperglycemic conditions in vivo [30,32]. As reported for metformin [33][34][35][36], the effects of CrPic are not attributed to increased expression of GLUT4 protein but rather its translocation and/or activation state [18,[37][38][39]. Combined, these results predict that during the hyperglycemic state Cr 3+ may functionally enhance insulin action by targeting the plasma membrane.…”

“…In particular, hexavalent chromium (Cr 6+ ), which is well recognized to pose an environmental health risk, has been shown to increase membrane fluidity [50]. Consistent with this membrane change having an insulin-like action on glucose transport, hexavalent chromium significantly stimulates glucose uptake into rat adipocytes [39]. Taken together with the data presented in this report, the extraordinary complexity of understanding chromium biology and toxicology certainly may involve an underappreciated cast of membrane lipids, including cholesterol.…”

Antidiabetogenic Effects of Chromium Mitigate Hyperinsulinemia-Induced Cellular Insulin Resistance via Correction of Plasma Membrane Cholesterol Imbalance

“…An increase in PM cholesterol was noted in the cells cultured in 25 mM glucose and the beneficial action of CrPic was attributed to lowering PM cholesterol content to that measured in control, 5-mM glucose, insulin-sensitive cells (12). As reported for metformin (41)(42)(43)(44), the effects of CrPic are not attributed to increased expression of GLUT4 protein but rather its translocation and/or activation state (45)(46)(47). In line with these observations, our studies herein support a shared mechanism for the beneficial effects of metformin and CrPic on cellular insulin sensitivity, with the regulation of PM cholesterol being a central component of this mechanism.…”

Chromium enhances insulin responsiveness via AMPK

“…An increase in plasma membrane cholesterol was noted in adipocytes cultured in 25 mM glucose, and the beneficial action of CrPic was attributed to lowering plasma membrane cholesterol content to levels measured in control, insulin-sensitive adipocytes cultured in 5 mM glucose [3]. As reported for metformin [38–41], the effects of CrPic are not attributed to increased expression of GLUT4 protein, but rather its translocation and/or activation state [2, 42–44]. In line with these observations, our studies herein suggest a shared mechanism for the beneficial effects of metformin and CrPic on cellular insulin sensitivity.…”