الفهرس 
Insulin ResistanceOnly 14 pages are availabe for public view
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Abstract
Nowadays, the incidence of IR is increasing worldwide, a trend that is largely attributable to lifestyle choices. Unhealthy nutritional patterns such as high consumption of fructose, the sweety poison, are related to these metabolic disorders. Several studies in humans support the relationship between high intake of fructose and hyperglycaemia, IR and type 2 diabetes. Due to its particular metabolic fate, fructose exerts specific effects on lipid and carbohydrate metabolism; moreover, HFD induces IR via a variety of pathogenic mechanisms such as ATP depletion, overproduction of inflammatory cytokines and mediators that cause oxidative stress and chronic inflammation (Goran et al., 2013)( O’Connor et al., 2015).
CR can significantly improve IR and T2DM, while the molecular mechanisms mediating this beneficial effect remain unclear (Gao et al., 2015).
So, we aimed from this study to clarify the effect of moderate CR in the protection against IR induced by HFD feeding in adult male Wistar albino rats and to assess the role of autophagy.
The rats included in this study were classified into 2 main groups, group I (control group): they are normal rats fed balanced animal diet and were left undisturbed but exposed to handling only for 70 days. group II (IR group): IR was induced by feeding HFD for 60 days.
Then, at the end of 60 days, blood samples from the retroorbital venous plexus were collected from all rats in group II to be sure that all rats had IR with exclusion of the non-insulin resistant rats from the study.
After that, group II was divided into 4 subgroups, each subgroup consisted of 6rats:
• group II (a): In this subgroup, the IR rats continued HFD for another 10 days.
• group II (b): In this sub group, the IR rats recieved moderate caloric diet (40% CR) for 10 days.
• group II (c): In this sub group, the IR rats recieved moderate caloric diet and treated with an autophagy inducer ”spermidine” 50mg /kg/day by I.P. injection for 10 days.
• group II (d): In this sub group, the IR rats recieved moderate caloric diet and treated with an autophagy inhibitor ”chloroquine” 10mg/kg/day by I.P. injection for 10 days.
Parameters chosen to assess IR and the protective effect of moderate CR included:
I. Calculation of body mass index
II. Estimation of fasting plasma glucose & serum insulin
III. Calculation of HOMA-IR
IV. Assessment of mRNA expression of Beclin-1(BCL-1) by Real-Time polymerase chain reaction (RT-PCR) in both hepatic and pancreatic tissues.
V. Histopathological examination of the pancreas
The obtained results of this study could be summarized as follow:
• HFD feeding in group IIa showed a significant increase in fasting plasma glucose, serum insulin, HOMA- IR, BMI, pancreatic BCL-1 mRNA expression and a significant decrease in hepatic BCL-1 mRNA expression. Additionally, the histopathological examination of the pancreas by H&E showed increase in β cell mass & count.
• 40% moderate caloric restriction in group IIb showed a significant decrease in fasting plasma glucose, serum insulin, HOMA- IR, BMI, pancreatic BCL-1 mRNA expression and a significant increase in hepatic BCL-1 mRNA expression. Also, the histopathological examination of the pancreas by H&E showed retuning of the β cells to its normal mass & count.
• Administration of spermidine in a dose of 50mg/kg/day for 10 day in combination with moderate CR showed a significant decrease in fasting plasma glucose, serum insulin, HOMA- IR, BMI, pancreatic BCL-1 mRNA expression and a significant increase in hepatic BCL-1 mRNA expression. Moreover, the histopathological examination of the pancreas by H&E showed normal β cell mass & count.
• Administration of chloroquine in a dose of 10mg/kg/day for 10 day in combination with moderate CR showed a significant increase in fasting plasma glucose, serum insulin, HOMA- IR, BMI, pancreatic BCL-1 mRNA expression and a significant decrease in hepatic BCL-1 mRNA expression. The histopathological examination of the pancreas by H&E showed increase β cell mass & count.
from the above results we can conclude that HFD induces IR and increases BW & BMI. Moreover, HFD induced IR supress hepatic autophagy and induces pancreatic autophagy. While, 40% moderate caloric restriction improves IR through activation of hepatic autophagy. Interestingly, restoration of hepatic autophagy by administration of spermidine improves IR & inhibition of hepatic autophagy by administration of chloroquine resulted in IR indicating a decrease in the protective effect of CR on IR. On the other hand, the situation is different with the pancreas as the level of fasting plasma glucose, serum insulin and HOMA-IR affects the β cell mass & counts through modulating β cell autophagy. So, we assume that the pharmacological induction or inhibition of autophagy have no direct effect on pancreatic autophagy for further studies.