D efinitions
Diabetes mellitus: An endocrine disease characterized by an elevated blood
glucose concentration. There are two major forms of diabetes mellitus:
type I, or insulin-dependent, and type II, or non-insulin-dependent. Type
I is caused by a severe lack or complete absence of insulin. Type II is
caused by resistance to insulin, that is, an inability to respond to physi-
ologic concentrations of insulin.
Fructose 2,6-bisphosphate: A metabolite of fructose 6-phosphate pro-
duced by the bifunctional enzyme 6-phosphofructokinase-2/fructose
bisphosphatase-2 (PFK-2/FBPase-2). It serves as an allosteric effector
that activates 6-phosphofructokinase-1 and inhibits fructose bisphos-
phatase-1, thus stimulating the movement of glucose through the gly-
colytic pathway and inhibiting gluconeogenesis.
Glucagon: A polypeptide hormone synthesized and secreted by the a-cells
of the islets of Langerhans in the pancreas. Glucagon is released in
response to low blood glucose levels and stimulates glycogenolysis and
gluconeogenesis in the liver.
Insulin: A polypeptide hormone synthesized and secreted by the P-cells of
the islets of Langerhans in the pancreas. Insulin is released in response
to elevations in blood glucose and promotes the uptake of glucose into
cells by increasing the number of GLUT 4 glucose transporters on cell
Protein kinase A: An enzyme that will phosphorylate target proteins. It is
activated by increased cAMP concentration in the cell that is a response
to the activation of adenylate cyclase by binding of certain hormones on
cell surfaces.
Every cell in the human body uses glucose as an energy source. Indeed, certain
cells have an obligate requirement for glucose to meet their energetic demands
(e.g., erythrocytes). Neurons, although can use alternative fuel sources under
extreme conditions (e.g., ketone bodies during prolonged starvation), have a
strong preference toward glucose utilization. Circulating levels of glucose must
therefore be maintained sufficiently high to meet the energy demands of the
body. Chronic elevations in blood glucose levels are also detrimental, being
associated with oxidative stress and glycation of cellular proteins. It has been
suggested that the latter mediate many of the complications associated with
chronic hyperglycemia, such as diabetic microvascular disease and retinopathy.
Despite diurnal variations in meal times, blood glucose levels are normally
maintained within a narrow range. This is made possible in large part by the
counter regulatory actions of the peptide hormones insulin and glucagon.
Insulin, secreted by the P-cells of pancreatic islets when blood glucose levels
increase, promotes glucose utilization and represses endogenous glucose
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