Share
هرمون اللبتين والاستقلاب : دراسة كيميانسيجية وكيمياحيوية شاملة في الحيوانات الطبيعية والمصابة بالسكري == Leptin And The Metabolism : A Comprehensive Histochemical And Biochemical Study In Healthy And Diabetic Animals
Author name:
سامح سمیر موسى عكیلة
Supervisor name:
سلمان شفیق سلمان | سامیة عباس علیوي
General topic:
Medicine
Specific topic:
Anatomy and Histology and Embryos
Degree:
Doctorate
University:
Mustansiriyah University
Language:
English
University location:
Baghdad
First pages:
19T1157 - p.pdf
Abstract:
The adipocytokine leptin is a major player in the pathogenesis of diabetes mellitus and obesity. Since its discovery around 20 years ago, leptin has been; and still is; the subject of extensive research.The current study was designed to examine the effects of physiological doses of leptin on major organs involved in metabolism. The anatomical, histochemical, physiological, and biochemical effects of leptin were studied in healthy animals and in animal models of type 1 and type 2 diabetes.Eighty male albino mice were divided into three groups. The first group (A) consisted of healthy non - obese non - diabetic animals, a subgroup (A1) of which received leptin therapy to study its effects under normal conditions without metabolic disturbances. In the second group (B), a model of diet induced obesity and insulin resistance was developed using a combination of high fat diet and low dose streptozocin injection. In one subgroup (B1), the effects of leptin were studied under dietary manipulation after the discontinuation of high fat diet. In other subgroups, leptin effects were examined with continuous HFD with (B3) and without (B2) concomitant metformin therapy. The third group animals (C) represented a type 1 DM model developed by high dose streptozocin injection. A subgroup (C3) served as model control, not receiving any hormonal therapy. The others two subgroups received leptin treatment with (C2) and without (C1) concomitant insulin therapy.Statistical parameters for the study included the body weight, food and caloric consumption, adiposity index and specific organ weights and weight ratios. The epididymal fat pad, liver and pancreas were examined for gross anatomical and histological changes. Adipose tissue and some pancreatic sections were stained with H&E, liver sections were stained with periodic acid schiff stain, other pancreatic sections were stained with modified Gomori's aldehyde fuchsin. Random blood sugar and serum lipid levels and insulin tolerance test were also studied as biochemical parameters.Leptin therapy in healthy non - obese animals resulted in a reduction in food consumption, body weight, adiposity index and white fat pads weight. It also caused a reduction in the diameter and surface area of epididymal adipocytes. Serum TGL and LDL levels were significantly reduced. iiiThe same effects were seen in group B animals that underwent dieting or received metformin, but not in ones receiving leptin alone. Animal models of type 1 DM showed a moderate response to leptin therapy alone but the response was dramatically enhanced when treatment was combined with insulin. Sever weight loss and polyphagia of type 1 DM were greatly ameliorated by leptin therapy and there was an improvement in fat pad weights and adipocyte measurements. The hepatic glycogen content and insulin sensitivity were greater in animals treated with leptin (A1), on diet and leptin (B1) or metformin (B3) and in animals on leptin with insulin (C1). This was associated with significantly lower levels of random blood sugar. The pancreatic islet surface area was markedly reduced while the ? - cell/ ? - cell ratio was increased in treated animals.Leptin therapy can alter body weight and adiposity index by affecting appetite and food consumption via central and peripheral mechanisms involving the control of feeding behavior and manipulating the processes involved in carbohydrate and lipid metabolism. It can also correct the metabolic disturbances of type 2 DM but requires the concomitant use of metformin and/or the manipulation of dietary content of fat and carbohydrates. Much of its influence arises from its ability to enhance insulin sensitivity.Leptin also has a sparing effect on hepatic glycogen, favoring in turn the use of fatty acids for energy expenditure. Leptin effects on blood glucose are insulin dependent in most cases but can be insulin - independent in type 1 DM by utilizing alternative metabolic pathways for energy expenditure and interacting with hyperglycemia - inducing hormones.
