2011 ADA Posters 1261-2041.indd - Diabetes

(t=5, t=10, t=15, t=30, t=60) and following cessation of stimulation (t=90
and t=120 minutes) to determine blood glucose and plasma insulin levels. To
exclude that the effects on glucose metabolism were stress-induced we also
measured plasma corticosterone levels.
In the 200 μA stimulated animals, plasma insulin levels signifi cantly
increased to 122% of base-line at onset of stimulation (t=5) compared to
sham stimulated animals whereas blood glucose values showed a slight (4%)
increase during the fi rst 15 min of stimulation. In contrast, stimulation at
lower intensity (100 μA) did not affect either measure. Plasma corticosterone
levels were not signifi cantly changed as compared to the sham and 100 μA
conditions and thus can not explain changes in insulin secretion or the slight
glucose rise.
These data suggest a role for the NAc in the regulation of glucose
metabolism and we hypothesize that the NAc controls the pancreas and
thereby insulin secretion via the central nervous system.
Supported by: ZonMW
& 1633-P
Synergism of Dopamine Agonist Plus GLP-1 Analog Therapy on
Improvement of Glucose Intolerance in Syrian Hamsters
MICHAEL EZROKHI, SHUQIN LUO, YELENA TRUBITSYNA, ANTHONY H. CIN-
COTTA, Tiverton, RI
Previous studies have demonstrated that timed daily treatment of
bromocriptine, a dopamine D2 receptor agonist, to insulin resistant animals
and humans improves postprandial insulin sensitivity. Such treatment
reduces post-meal or post-glucose challenge levels of glucose while
simultaneously markedly reducing hyperinsulinemia. GLP-1 analogs such
as exendin-4, are known to enhance glucose – mediated insulin secretion
and reduce glucagon secretion. Therefore, the possibility exists of a positive
interaction between such a postprandial insulin sensitizing mechanism
with such an enhanced postprandial insulin secretory response to improve
glucose intolerance.
To test such a postulate, glucose intolerant insulin resistant Syrian
hamsters weighing 200 grams were treated with either vehicle (N=20) or
bromocriptine (4 mg/kg; N=20) for 2 weeks and then each group was further
subdivided into 2 groups and treated with either vehicle or exendin-4 (4 µg/
kg) just prior to being subjected to a glucose tolerance test (GTT) (3g/kg).
Relative to the vehicle/vehicle (control), bromocriptine markedly reduced the
insulin area under the curve (AUC) by 39% (from 1311 ± 177 to 796 ± 119
ng*min/ml) (P=0.03) while reducing the glucose AUC by 21% (from 42576 ± 3889
to 33752 ± 2763 mg*min/dl) (P