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The many roles of insulin

Insulin is the key hormone in glucose homeostasis. This peptide has a
number of key functions, including promoting the uptake of glucose by
cells throughout the body. Insulin, secreted by the β-cells of the pan-
creas, is transported to and binds to its receptor, a tyrosine kinase en-
zyme consisting of two extracellular α-subunits and two β-subunits that
span the cell membrane. These receptors are ubiquitous, with almost
every cell in the body expressing them. 9 10

When insulin binds to the receptor, it phosphorylates various intracel-
lular proteins, activating a cascade of events resulting, among other
effects, in stimulated glucose uptake via active transport (Figure 1). 9 10

Figure 1: Schematic diagram showing insulin-induced glucose uptake by a cell. 9 10

As a first step, insulin activates the hexokinase enzyme, which phos-
phorylates glucose, effectively trapping it within the cell. In hepato-
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cytes, insulin inhibits the activity of glucose-6-phosphatase, the enzyme
responsible for liberating free glucose from the glucose-6-phosphate
originating from glycogen (glycogenolysis) and de novo glucose syn-
thesis (gluconeogenesis). As well as preventing the release of glucose
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from the hepatocytes, insulin also activates several of the enzymes
that are directly involved in glycolysis and glycogen synthesis, includ-
ing phosphofructokinase and glycogen synthase, respectively. When
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glucose is abundant, insulin stimulates the liver to convert it to glycogen
for storage and later use. 12

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