This was primarily a result of impaired suppression of endogenous glucose release and to a lesser extent of reduced initial splanchnic sequestration of ingested glucose.
41 However, the rate of meal appearance as assessed by a radiolabeled standard meal was lowered, suggesting that perhaps splanchnic sequestration of meal-derived glucose may play a role in lowering glucose concentrations.
The intracellular sequestration of the insulin-sensitive glucose transporter isoform GLUT4 is required for the generation of a storage compartment from which it can be recruited to the plasma membrane (PM) rapidly upon activation of insulin signalling [ 9].
In vitro and in vivo evidence summarized here suggests that this is effected by interfering in the utilization of glucose and glucose-6-phosphate, and sequestration of iron by ferritin.
Rat WT-GKRP and P446L-GKRP behaved quite differently: both variants responded to high glucose by diminished sequestration of GCK but showed no effect of the P446L variant on nuclear localisation or GCK sequestration.
In hepatocytes, GK is subtly regulated by GKRP, a 68-kDa primarily nuclear protein that inactivates and facilitates the sequestration of GK in the nucleus when glucose levels are low (29– 34).
Indeed, the half-maximal effect of glucose on ATP elevation at 5.2 mmol/l is almost identical to the 5.5 mmol/l reported for Ca2+ sequestration into the endoplasmic reticulum [ 43].
Upon the application of glucose, [Ca2+]i often decreased slightly before being elevated, which was suggested to be due to the ATP-activated SERCA-dependent sequestration of [Ca2+]i in the ER (Marie et al. 2001).
Cortisol, the primary stress hormone, increases sugars (glucose) in the bloodstream, enhances the brain's use of glucose, and increases the availability of substances that repair tissues.
Sequestration of glucokinase in the hepatocyte nucleus at basal glucose concentrations is regulated by binding to its inhibitory protein (GKRP) [8 10].
