PMID:30146176

Citation	'Chakera, AJ, Hurst, PS, Spyer, G, Ogunnowo-Bada, EO, Marsh, WJ, Riches, CH, Yueh, CY, Markkula, SP, Dalley, JW, Cox, RD, Macdonald, IA, Amiel, SA, MacLeod, KM, Heisler, LK, Hattersley, AT and Evans, ML (2018) Molecular reductions in glucokinase activity increase counter-regulatory responses to hypoglycemia in mice and humans with diabetes. Mol Metab '
Abstract	Appropriate glucose levels are essential for survival; thus, the detection and correction of low blood glucose is of paramount importance. Hypoglycemia prompts an integrated response involving reduction in insulin release and secretion of key counter-regulatory hormones glucagon and epinephrine that together promote endogenous glucose production to restore normoglycemia. However, specifically how this response is orchestrated remains to be fully clarified. The low affinity hexokinase glucokinase is found in glucose-sensing cells involved in glucose homeostasis including pancreatic β-cells and in certain brain areas. Here, we aimed to examine the role of glucokinase in triggering counter-regulatory hormonal responses to hypoglycemia, hypothesizing that reduced glucokinase activity would lead to increased and/or earlier triggering of responses.
Links	PubMed Online version:10.1016/j.molmet.2018.08.001
Keywords
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:HXK4		GO:0032811: negative regulation of epinephrine secretion	ECO:0000315:		P		Figure 4g shows that when GCK is knocked out in mice, plasma epinephrine levels rise significantly.	complete CACAO 13356
MOUSE:HXK4		GO:0004340: glucokinase activity	ECO:0000315:		F		Supplementary figures 1a and 1b show that GCK mutant mice show reduced glucose phosphorylating activity in the liver and pancreas.	complete CACAO 13359

References

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