Glucose Homeostasis Pathway Suite Network

Pathway Suite for the Glucose Homeostasis-related Regulatory and Signaling Pathways

Pathway Suite for the Metabolism of Glucose and Related Molecules Pathways

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Glucose is an essential fuel and the primary energy supply for the brain. Glucose homeostasis – the balanced maintenance of glucose levels, transport and processing as demanded by the needs of cells, tissues and organs, relies on a finely-tuned, coordinated network of metabolic, regulatory and signaling pathways. The metabolic pathways are responsible for the oxidation and conversion of glucose, and its storage and/or biosynthesis as necessary. Regulatory pathways provide for glucose delivery and the secretion of hormones whose signaling activates downstream cascades. The resulting changes in gene expression assure the adequate implementation of responses necessary to maintain proper levels of circulating glucose and meet the energy-consuming or energy-saving demands of the system. Disturbance of glucose homeostasis has devastating consequences and has been associated with many conditions. The collection of currently available interactive pathway diagrams pertinent to glucose homeostasis are diagrammatically captured and highlighted for the metabolic pathways and for the regulatory and signaling ones.

Click here to explore the Pathway Suite for the Glucose Homeostasis-related Regulatory and Signaling Pathways.

Click here to explore the Glucose and Related Molecules Metabolism Pathways Suite for pathways involved in oxidation, conversion, storage or biosynthesis of glucose.

Glucose is a vital cellular fuel and constitutes the main energy source for the brain. The levels of glucose on both a cellular and a systemic scale are controlled by a complex network of metabolic, regulatory and signaling pathways. This suite of interactive pathway diagrams covers signaling and regulatory pathways pertinent to glucose homeostasis.

Click here to explore the metabolic pathways involved in glucose oxidation and conversion which also contribute to the delicate balance of glucose homeostasis in the body.

Disregulation of a number of glucose homeostasis-related metabolic, regulatory and signaling pathways has been linked to Type 2 Diabetes. Click here to explore the Type 2 Diabetes Pathway Suite for more information on pathways of relevance to this condition.
To link to the Diabetes Disease Portal, click here

Regulatory pathways
Insulin Secretion Pathway		Insulin Responsive Facilitated Sugar Transporter Mediated Glucose Transport Pathway
	In response to elevated glucose, pancreatic beta cells release insulin. Insulin secretion is biphasic: an initial “triggering” phase dependent on ATP-sensitive potassium channels is followed by an “amplifying” phase largely independent of KATP channels. Click here to explore this vital and complex regulatory pathway.		Uptake of glucose in the heart, skeletal muscle and adipose tissues is mediated by the Slc2a4/Glut4 transporter. Insulin prompts trafficking of transporter-containing vesicles to the plasma membrane where exocytosis increases the Glut4 at the membrane. The PI3K-Akt pathway downstream of the insulin receptor may play a role via Akt2. Click here to explore this essential component of glucose homeostasis.

Signaling Pathways
Insulin Signaling Pathway		Glucagon Signaling Pathway
	Secreted insulin binds to its receptor to initiate a signaling pathway which plays essential roles in both glucose and energy homeostasis. The pathway activates two intracellular cascades – the PI3K-Akt and Raf/Mek/Erk MAPK pathways – to ultimately carry out insulin’s downstream effects. Click here to explore this important signaling pathway and the cascades it triggers.		In response to low glucose, pancreatic alpha cells release glucagon by incompletely understood mechanisms. Glucagon signaling activates the protein kinase A (PKA) pathway to stimulate glucose-producing, while inhibiting glucose-consuming, metabolic pathways. Click here to explore this important signaling network.

Click here to explore the glucose homeostasis-related regulatory and signaling pathways which also contribute to the delicate balance of glucose homeostasis in the body.


Glucose storage
	Glycogen biosynthetic pathway
		Metabolism of glycogen, the storage form of glucose, takes place primarily in the liver and muscle. Muscle glycogen is used to provide local energy while glycogen in the liver supplies fuel to extrahepatic tissues. Click here to explore this important metabolic pathway.

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Glucose Oxidation and Conversion

Glycolysis Pathway

Pyruvate Metabolic Pathway

Glycolysis represents the first round of glucose breakdown whose end product, pyruvate can have multiple fates. Click here to explore how glucose is converted to pyruvate in one of the best characterized biochemical pathways.

Pyruvate metabolism plays a central role in glucose and energy homeostasis. Pyruvate can be converted to acetyl-CoA, the precursor of the energy producing citrate cycle, but also of energy storing fatty acid biosynthesis or to oxaloacetate, a citrate cycle intermediate and precursor of gluconeogenesis. Click here to explore this important intersection node of several metabolic pathways.

Pentose Phosphate Pathway

Hexosamine Biosynthetic Pathway

This pathway represents an alternate route of glucose oxidation accounting for ~10-20%. It produces reducing equivalents and a precursor for nucleotide and nucleic acid synthesis. Click here to explore this important metabolic pathway.

Approximately 2-5% of the fructose-6-phosphate, the isomer of glucose-6-phosphate, is diverted to the production of UDP-N-acetylglucosamine rather than being converted to pyruvate via glycolysis. UDP-GlcNAc is the unique donor for the O-linkage of a single N-acetylglucosamine (O-GlcNAc) to many cytoplasmic and nuclear proteins. Click here to explore the biosynthetic pathway of this important modulator that, by virtue of the broad functionality of its targets, many consider a signaling molecule.