The Role of Cholinergic Signaling for Mediating the Effects of GIP and/or Xenin-25 on Insulin Secretion
Status:
Completed
Trial end date:
2015-05-01
Target enrollment:
Participant gender:
Summary
Glucose-dependent insulinotropic polypeptide (GIP) is a hormone produced in the intestine. It
is released immediately after meal ingestion and increases insulin release. This, in turn,
helps reduce blood glucose levels. This circuit does not work properly in humans with type 2
diabetes mellitus (T2DM).
We have previously shown that a peptide called xenin-25 can amplify the effects of GIP on
insulin secretion in humans. However, xenin-25 no longer does this when humans develop T2DM.
Thus, it is important to understand how xenin-25 works in humans without T2DM so we know why
it does not work in humans with T2DM.
Acetylcholine is molecule produced by specific types of nerves. The effects of acetylcholine
can be blocked by a drug called atropine. We have previously shown in mice that atropine
prevents the ability of xenin-25 to increase the effects of GIP on insulin release. The
purpose of this clinical trial is to determine if atropine also blocks the effects of
xenin-25 in humans without T2DM. If it does, then impaired acetylcholine signaling may be one
of the reasons humans develop T2DM and it could be possible to develop drugs that bypass this
defect and increase insulin release in humans with T2DM.