Research Publications - College of Medicine and Health Science

Diabetic neuropathy and retinopathy
Changes in gene expression in the diabetic eye,
in sympathetic and dorsal root ganglia, corpus
cavernosum and vascular tissues were investigated
by low density expression array in studies
funded by the Emirates Foundation and the
FMHS by Professors Adrian and Morrison. Several
interesting early changes in gene expression
were seen, particularly in the retinas of diabetic
animals. Ongoing studies include confirmation
of the expression changes using fast real-time
RT-PCR and immunocytochemistry for the
protein products of these genes in collaboration
with Dr. Eric Mensah-Brown in the Department
of Anatomy. Marked changes in gene expression
have been documented. For example, in the
pelvic ganglia from diabetic animals the expression
of vasoactive intestinal polypeptide (VIP)
and neuronal nitric oxide synthase (nNOS) are
dramatically reduced in diabetic animals, while
expression of another transmitter, Cholecystokinin
(CCK) is dramatically increased. Since VIP
and nNOS play a role in penile erection and in
control of bladder function, these changes are
likely to explain the erectile dysfunction and for
urinary retention that are seen in diabetics.
Early changes in expression of several genes, including
calpain 3, and several crystallins, in the
retina have been seen in three different models
of diabetes in the rat. Changes in expression
of these genes are likely to be involved in the
pathophysiology of cataracts, diabetic retinopathy
and glaucoma.
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hormones in diabetes and obesity
Enteroendocrine L-cells produce glucagon gene
products (GLP-1 and oxyntomodulin) as well
as PYY. All are satiety factors. GLP 1 is also an
incretin. The number of L-cells and hormonal
contents increases distally through the gut
with highest concentrations in the rectum. We
have previously shown that intracolonic infusion
of bile salts in humans causes secretion of
L-cell hormones, triggered via TGR5 membrane
receptors. Together with colleagues in the
Department of Internal Medicine, Prof. Adrian
has been investigating release of these lower GI
hormones in obese patients with type 2 diabetes
mellitus. Using a simple and well-tolerated
agent, this group has shown substantial increases
in circulating concentrations of GLP-1,
PYY and insulin. The release of the lower GI
hormones resulted in a fall in circulating glucose
levels and a marked reduction in spontaneous
caloric intake of a subsequent meal. This mechanism
is likely to be valuable in the treatment
of type 2 diabetes and obesity. Investigations
focused on the improvement of diabetic status
and reduction in body weight with chronic
administration of bile salts are planned.
Relative expression of mRNA for VIP, neuronal NOS (NOS1), NOS2, somatostatin, and CCK in pelvic ganglia from control rats and
diabetic rats 12 weeks after treatment with streptozotocin. Real-time RT-PCR confirmation of low density gene expression array
data, n=8 in each group.
Department of Physiology
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