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Figure 2. Major sites of glucose production in response to overnight fasting

The kidneys also play an important role in the counter-regulatory re-
sponse to hypoglycaemia, with both increased renal gluconeogenesis
and, to a lesser extent, decreased glucose uptake, acting to maintain
glucose circulating levels. The contribution of renal gluconeogenesis
11
to total gluconeogenesis is also substantially greater in hypoglycaemia,
with up to a third of all glucose produced coming from the kidneys.
12
Furthermore, in patients with type 2 diabetes, in whom hepatic glyco-
gen stores are depleted or glycogenolysis pharmacologically inhibited,
a renal counter-regulatory response may be even more pivotal.

Kidney function and insulin kinetics

The production of insulin by the pancreas in response to feeding facili-
tates the uptake of glucose into the liver, fat and skeletal muscle to
maintain euglycaemia post-prandially in healthy individuals. During
fasting, insulin production is suppressed; triggering the release of glu-
cose to ensure the brain receives the constant supply of glucose that it
requires to function normally. A similar balance can be approximated
with pharmacotherapy in patients with type 2 diabetes using exoge-
nous insulin, sensitizers or secretogogues to achieve and sustain glu-
cose control.

31