INGAP Peptide - An
Initiator of Beta Cell Growth
You
will be hearing more about INGAP in upcoming newsletters
Recent
studies have shown that induction of islet neogenesis from adult
pancreatic stem cells has the potential for restoring beta cell mass
in diabetes.
We
have previously hypothesized that these stem cells can develop along
either a neural or a neuroendocrine path. The factors regulating this
development are unknown. We examined the role of INGAP peptide in
islet neuroendocrine cell development in vivo. Forty dogs (20 males,
20 females) were randomly divided into 4 groups. Group 1 received
daily IM injections of vehicle alone, while the other 3 groups
received 0.5, 1.5 or 10 mg/kg injections of INGAP peptide. After 30
days of treatment the animals were sacrificed and pancreatic tissues
collected. Analysis was performed with ImagePro software on confocal
microscopy images of tissues stained for insulin, the essential islet
transdifferentiation transcription factor PDX-1 and the pan-neuroendocrine
marker PGP9.5.
The
results showed a significant (p<0.001) increase in the percentage
of insulin positive cells in animals treated with INGAP peptide
(p<0.001, ANOVA, Table 1), with 1.5 mg/kg being the most effective
dose, more than doubling controls (Dunnett’s Test, p<0.05). PGP
9.5 was increased, based on stain intensity, in large ducts of treated
animals, suggesting development of neuroendocrine cells from ductal
elements in response to INGAP. PDX-1 was increased in 1.5mg/kg-treated
pancreas especially in isolated cells and duct epithelium.
These
results indicate that adult islet stem cells in pancreas of normal
dogs are induced to develop along a neuroendocrine pathway in response
to INGAP peptide. The expression of PDX-1 and PGP 9.5 in duct cells
suggests that INGAP is an initiator of neuroendocrine cell and PDX-1
expression in the path to islet neogenesis.
ENDO 2002 [P1-27]
%
Insulin Positive Area
Control
0.5mg/kg INGAP 1.5mg/kg
INGAP 10mg/kg INGAP
1.2±0.1
1.8±0.2*
2.9±0.2*†
1.5±0.2
