Abstract
Protein kinase (PK) has always been an attractive target for the discovery of
new drugs. However, this year is significant for PK therapeutics since it marks the 20th
anniversary of the FDA’s approval of the first PK drug, imatinib, which was approved
in 2001 as the first protein kinase drug. GSK-3 is a serin protease protein kinase that
plays a key role in glucose homeostasis in our body. It also regulates insulin resistance
and the expression of glucose transporter. In type 2 diabetes mellitus (T2DM), glucose
homeostasis in our body becomes jeopardized due to poor glucose utilization by the
liver, muscle, and adipose tissue. GSK-3 is generally overexpressed among obese
diabetics; therefore, the GSK-3 inhibitor might be a better therapeutic target for the
discovery of new antidiabetic treatment. The lithium salt was experimented with as a
GSK-3 inhibitor using different animal models to evaluate its antidiabetic activity and
prove its action on glucose regulation inside cells. However, owing to the significant
toxicity of lithium salt in the development of colorectal cancer, the WNT signalling
pathway is inhibited. Currently, the major pharmaceutical companies are trying to
design and synthesize some GSK-3 inhibitors that are safe and effective for diabetics.
Some of these molecules are in the initial stages of the clinical trial to assess their
effectiveness. In this chapter, the role of GSK3 in the regulation of insulin release and
glucose metabolism was explained with a number of schematic representations in order
to facilitate biomedical scientists in the drug discovery process.
Keywords: Diabetes mellitus, Glycogen synthase, GSK-3, GSK-3 inhibitor, Protein kinase.
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