Researcher have greatly advanced medical and biochemical
understanding of how insulin works and what happens when
it is lacking. In a new study, researcher describe a key
player in the defense mechanism that safeguards us
against excessive insulin in the body. Although insulin
is one of the most essential hormones, whose
insufficiency can result in death, too much insulin can
also be deadly. Patients who are treated with insulin or
drugs that stimulate insulin secretion often experience
hypoglycemia, a condition that if gone unrecognized and
untreated can result in seizures, coma and even death,
which collectively define a condition called insulin
shock. The body's natural defense or safety valve that
reduces the risk of insulin shock. That valve is a
metabolic enzyme called fructose-1,6-bisphosphate
phosphatase or FBP1, which acts to control
gluconeogenesis, a process in which the liver
synthesizes glucose during sleep and secretes it to
maintain steady supply of glucose in the bloodstream.
Some antidiabetic drugs, such as metformin, inhibit
gluconeogenesis but without apparent ill effect.
Children born with a rare, genetic disorder in which
they do not produce sufficient FBP1 can also remain
healthy and live long lives. But in other cases, when
the body is starved for glucose or carbohydrates, an
FBP1 deficiency can result in severe hypoglycemia.
Without a glucose infusion, convulsions, coma and
possibly death can ensue. The roles of FBP1, researchers
created a mouse model with liver specific FBP1
deficiency, accurately mimicking the human condition.
Like FBP1-deficient children, the mice appeared normal
and healthy until fasted, which quickly resulted in the
severe hypoglycemia and the liver abnormalities and
hyperlipidemia described above. This peptide works like
an insulin mimetic, activating AKT. When injected into
mice that have been rendered insulin resistant, a highly
common pre-diabetic condition, due to prolonged
consumption of high-fat diet, the peptide can reverse
insulin resistance and restore normal glycemic control. |