What happens if GSK3 is inhibited?

GS inhibition by GSK-3β leads to a decrease in glycogen synthesis in the liver and muscles, along with increased blood glucose or hyperglycemia. This is why GSK-3β is associated with the pathogenesis and progression of many diseases, such as diabetes, obesity, cancer, and Alzheimer’s disease.

How does GSK3 affect glycogen synthase?

The GSK3 task exceeds being a simple kinase that deactivates the Glycogen Synthase enzyme and obstructs glycogen synthesis. GSK3 is a multitasker protein, for until now it has been found to regulate more than 25 transcription factors and over 25 non-transcription factor proteins [29].

How is GSK3 regulated?

GSK3 has traditionally been considered to be largely a cytosolic protein. However, GSK3 is also present within the mitochondria and nucleus, as well as other subcellular compartments, where its levels and/or activation state can be regulated by localized signaling activities.

Can GSK3 phosphorylate Akt?

GSK3 has been shown to phosphorylate several upstream and downstream components of the PI3K/AKT/mTOR signalling network, including AKT itself, RICTOR, TSC1 and 2, PTEN and IRS1 and 2, with the potential to apply feedback control within the network.

Does insulin activate GSK3?

Insulin was found to induce a marked phosphorylation of both GSK3 isoforms in WT control mice (Figure 2B).

Does Glycogenolysis occur in muscle?

Glycogenolysis takes place in the cells of the muscle and liver tissues in response to hormonal and neural signals. In myocytes (muscle cells), glycogen degradation serves to provide an immediate source of glucose-6-phosphate for glycolysis, to provide energy for muscle contraction.

Where is GSK3B located?

Glycogen synthase kinase 3 beta, also known as GSK3B, is an enzyme that in humans is encoded by the GSK3B gene. In mice, the enzyme is encoded by the GSK-3β gene….

How is Akt activated?

Akt activation is governed by a dual regulatory mechanism in which it is first recruited to the cellular plasma membrane by PIP3 through a direct interaction with the PH domain of Akt. For example, Akt can inactivate cell cycle inhibitors p27kip1 and p21cip1 to allow G1/S progression5.

What type of enzyme is glycogen synthase?

UDP-glucose-glycogen glucosyltransferase
Glycogen synthase (UDP-glucose-glycogen glucosyltransferase) is a key enzyme in glycogenesis, the conversion of glucose into glycogen. It is a glycosyltransferase (EC 2.4. 1.11) that catalyses the reaction of UDP-glucose and (1,4-α-D-glucosyl)n to yield UDP and (1,4-α-D-glucosyl)n+1.

How does insulin affect GSK3?

Insulin has been demonstrated to cause inactivation of GSK-3, both in vivo (3,4) and in several cell types (5–7). The mechanism of inactivation is associated with phosphorylation of the specific serine residues Ser21 and Ser9 in GSK-3 isoforms α and β, respectively.

What does insulin deficiency cause?

Insulin deficiency results in hyperglycaemia. The effects of hyperglycaemia are salt and water depletion due to an osmotic diuresis, weight loss, tiredness, vomiting, hypotension, infections, hyperventilation (due to ketoacidosis) and impaired conscious level and coma.