الفهرس 
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Abstract
Diabetes mellitus (DM) is one of the most prevalent and extreme metabolic disorders and
possibly one of the oldest human-known diseases. DM has become the world’s fifth leading cause
of death, and the International Diabetes Mellitus Federation estimated that 592 million people will
suffer from diabetes mellitus worldwide by 2035. Weight and type 2 diabetes mellitus (T2DM)
are closely related.
Not only does weight exacerbate hyperglycemia through the process of insulin resistance,
but it also raises the risk of hyperlipidemia. Improvement in glucose control has been linked to
body weight control. Cognitive deficiency development is associated with an unhealthy diet and
lack of exercise, which can lead to obesity, metabolic syndrome, and the development of T2DM.
Diabetics who have long-term T2 DM have a substantially elevated chance of developing cognitive
disability.
The current study was created to investigate the potential contribution of metformin,
liraglutide and pramlintide in the prevention of inflammatory processes associated with insulin
resistance and the control of diabetes-related obesity and cognitive impairment in high-fat dietstreptozotocin diabetic rat model.
Materials and methods:
Fifty male Wistar rats were randomly subdivided into four groups (n = 10 in each group):
1- G I (NG): normal control group was fed normal chow.
2- G II (HFD/STZ): after induction of T2 DM, rats received (0.6 mg/kg/day) of normal saline
subcutaneous (SC) injection for 6 weeks.
3- G III (HFD/STZ+P.): after being diabetic, rats received pramlintide (200 μg/kg/day SC.) for 6
weeks.
4- G IV (HFD/STZ+L.): after being diabetic, rats received liraglutide (0.6 mg/kg/day SC.) for 6
weeks.
5- G V (HFD/STZ+M.): after being diabetic, rats received metformin (200 mg /kg/day orally) for
6 weeks.Summary & Conclusion
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Results:
HFD/STZ+ P group and HFD/STZ+ L group revealed no significant difference in insulin
resistance when compared to each other, with significant improvement in insulin resistance as
compared to HFD/STZ group and HFD/STZ+ M group.
Moreover, a slightly significant difference between HFD/STZ+ P group and HFD/STZ+ L
group in lipid profile results and weight of visceral fat, with more improvement noticed in
HFD/STZ+ L group and a significant decrease when compared to NG, HFD/STZ group and
HFD/STZ+ M group.
Our result reveals a prominent increase in the RAMP1 expression in the pramlintide-treated
group with a deceased expression in the other groups. A noticed decrease in AMPK expression in
pramlintide and liraglutide-treated groups, with increase expression in a metformin-treated group.
A notice over expression of PI3/AKT protein with a down expression of GSK3 β in both
pramlintide and liraglutide treated groups. There was a dramatic decrease in TLR4 expression in
the pramlintide and liraglutide-treated groups, with a slight decrease in the metformin-treated
group. A noticed decrease in TNF-α expression in all treated groups, with a noticeable decrease in
TTBK1 expression in the pramlintide and liraglutide-treated groups, with a slight decrease in the
metformin-treated group.
In addition, no significant difference between HFD/STZ+ P group and HFD/STZ+ L group
as regards cognition tests when compared to each other and, when compared to NG, with a
statistically significant decrease when compared to HFD/STZ group and HFD/STZ+ M group.
Also, a statistically significant decrease in tau histological examination in all treated groups
when compared to the diabetic group. With a slight significant decrease in tau histological
examination between HFD/STZ+ P group and HFD/STZ+ L group.
Conclusion:
Noteworthy, the present study demonstrated the benefits of pramlintide, liraglutide, and
metformin in ameliorating neuronal insulin resistance and CD signs and reversing the impairment
of AKT and GSK-3β phosphorylation and ameliorated tau hyperphosphorylation with anSummary & Conclusion
improvement of obesity in type 2 DM rats. The outcomes of the completed research supported the
neuroprotective effects of pramlintide and liraglutide, while metformin was slightly less effective.
Our research approved that GLP-1 and amylin analogues both can decrease blood glucose
levels by improving insulin resistance and glucose transport through the PI3K/AKT passway, a
central factor in diabetes treatment. Furthermore, our earlier work indicated that there was a local
downregulation of brain AMPK in the hypothalamus by both amylin and GLP-1, which help in
decreasing body weight. Also, our research was one of the few research projects to discuss the
relationship between amylin and brain GSK-3β in improving cognitive disorders associated with
T2DM.
Home message:
Our drugs were developed to fill a gap in the marketplace in the DM and obesity field. All
of previous factors suggest that pramlintide and liraglutide are promising anti-diabetic medications
that may work through several mechanisms to prevent cognitive disorders associated with DM and
control associated obesity more effectively than the widely prescribed medication metformin.
Future studies:
Before these medications are used extensively in humans, more research should be done to
assess their side effects and their effects when taken for a longer period of time.
Funds:
This research was funded by faculty of medicine, Sohag university.