Biochemistry Answer-4

(B) GLP-1 is derived from the product of the
proglucagon gene. This gene encodes a preproprotein
that is differentially cleaved
depending on the tissue in which it is synthesized.
In the gut, prohormone convertase 1/3
action leads to release of several peptides
including GLP-1. On nutrient ingestion GLP-1
is secreted from intestinal enteroendocrine Lcells.
Bioactive GLP-1 consists of two forms:
GLP-1(7-37) and GLP-1(7-36) amide, where the
latter form constitutes the majority (80%) of
the circulating hormone. The primary physiologic
responses to GLP-1 are glucose-dependent
insulin secretion, inhibition of glucagon
secretion, and inhibition of gastric acid secretion
and gastric emptying. The latter effect will
lead to increased satiety with reduced food
intake along with a reduced desire to ingest
food. The action of GLP-1 at the level of insulin
and glucagon secretion results in significant
reduction in circulating levels of glucose following
nutrient intake. The glucose-lowering
activity of GLP-1 is highly transient as the halflife
of this hormone in the circulation is less
than 2 minutes. Removal of bioactive GLP-1 is
a consequence of N-terminal proteolysis catalyzed
by DPP IV. DPP IV is also known as the
lymphocyte surface antigen CD26 and has
numerous activities unrelated to hormone inactivation.
Although targeting compounds that
can inhibit the enzymatic action of DPP IV
would seem like ideal candidates for treating
the hyperglycemia of uncontrolled diabetes,
there are several unknowns associated with
DPP IV inhibition. One of these issues is the fact
that GLP-1 is only one of the many known substrates
for DPP IV cleavage. Thus, prolonged
inhibition of DPP IV enzymatic activity may
have unexpected consequences unrelated to
control of hyperglycemia. DPP IV is not known
to hydrolyze glucagons (choice A), insulin
(choice C), IGF-I (choice D), nor pancreatic
polypeptide (choice E).

Posted in: Biochemistry Answer