الفهرس 
Introduction
Insulin and metabolismOnly 14 pages are availabe for public view
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Abstract
Type 1 diabetes mellitus (T1DM) is a multifactorial autoimmune disease which is characterized by T-cell mediated destruction of the insulin secreting β cells in the pancreatic islets. The destructive process leads to severe insulin depletion that results in hyperglycemia because of hepatic overproduction of glucose by glycogenolysis and gluconeogenesis and decreased cellular uptake of glucose from circulation.
T1DM remains a major global health problem especially in the developing countries in spite of the availability of many antidiabetic drugs because they have limited efficacy and certain adverse effects. This leads to an increased demand of research on antidiabetic natural products such as medicinal plants that produce minimal or no side effects. Unfortunately, phytotherapy is not yet included in the evidence-based medicine, especially with respect to diabetes mellitus therapy. Studies to reveal the mode of action of potential antidiabetic plants will definitely give scientific and systematic approach for the use of these plants as hypoglycemic agents.
Streptozotocin (STZ) is frequently used to induce experimental T1DM and its diabetic action results from its highly specific cytotoxic action on β cells by increased production of oxygen free radicals that results in oxidative stress.
Balanites aegyptiaca is a widely distributed African plant of medicinal interest. In Egyptian folk medicine, its fruit mesocarp is commonly used as an oral antidiabetic drug. Petroselinum sativum is a cultivated variety of parsley and traditionally was used as carminative, abortifacient and anti-hypertensive agents. Until now, no data in the literature could be found about the antioxidant influences of Balanites aegyptiaca extracts in normal and diabetes-induced experimental models or its possible hypoglycemic effects on normal animals. Although there are few published articles about the antidiabetic effects of Petroselinum crispum extracts on the diabetic and normal animals and also their antioxidant effects on diabetic animals, but no work has been done to study the antidiabetic and antioxidant properties of Petroselinum sativum extracts in the diabetic or normal animals. For these reasons, the current study has been undertaken to examine the possible antidiabetic and antioxidant effects of Balanites aegyptiaca fruits and Petroselinum sativum leaves aqueous extracts in STZ-induced diabetic (hyperglycemic) and normal (normoglycemic) rats in a hop to transmit the results for the human use.
To achieve these objectives, the influences of both extracts on body weight (BW), and on plasma glucose, insulin, total antioxidant capacity (TAC) and malondialdehyde (MDA) levels, and on liver-pyruvate kinase (L-PK) level were assessed. Furthermore, the weight and the histopathological changes of pancreas were studied, and the pancreatic islet size was measured in the different experimental groups.
After preparation of the extracts and induction of diabetes using STZ, 60 adult male rats in this study were divided into 6 groups, 10 rats each, in two experiments having 45 days duration. Experiment 1 was planed to assess the possible hypoglycemic and antioxidant effects of Balanites aegyptiaca fruits and Petroselinum sativum leaves aqueous extracts on normal rats and it included normal control (NC), Balanites aegyptiaca extract-treated normal (BAETN) and Petroselinum sativum extract-treated normal (PSETN) groups. While experiment 2 was constructed to estimate the possible antidiabetic and antioxidant effects of Balanites aegyptiaca fruits and Petroselinum sativum leaves aqueous extracts on STZ-induced diabetic rats, and it included diabetic control (DC), Balanites aegyptiaca extract-treated diabetic (BAETD) and Petroselinum sativum extract-treated diabetic (PSETD) groups. At the end of the experiments, the live BW of the overnight-fasted rats was recorded and the blood samples were collected followed by separation of the plasma. After that, the rats were sacrificed and the liver tissue was excised, rinsed in ice-cold physiological saline and then homogenized. The plasma glucose, TAC and MDA levels and L-PK level were measured colorimetrically using spectrophotometer, while the plasma insulin level was measured by enzyme-linked immunosorbant assay (ELISA) reader using specific ELISA kit.
After scarification and evisceration of the rats, the pancreas was taken from each animal, rinsed in normal saline and dried, followed by measurement of pancreas weight for each animal. Pancreas weight per 100 gm BW was calculated in the various experimental groups to make a functional comparison of weight loss and gain. A pancreas biopsy specimen from each rat was obtained and prepared for staining with hematoxylin and eosin and then examined under light microscope. After that, the sizes of 100 islets were measured in each group and the mean size was calculated.
This study showed the following results:
(1) The mean final BW of the BAETN and PSETN groups was slightly higher than that of the NC group, but the increase was non significant. A high significant decrement in the mean final BW of the DC group was observed in comparison with the NC group. The mean final BW of the BAETD and PSETD groups were significantly greater than that of the DC group. In the BAETD group, the mean final BW exhibited more obvious enhancement than that detected in the PSETD group.
(2) A non significance difference was found between the mean plasma levels of glucose and insulin and L-PK level of the NC group versus those of the BAETN and PSETN groups. The DC group was characterized by a high significant increment in its mean plasma glucose level and a high significant decrement in its mean plasma insulin and L-PK levels as compared with the NC group. Balanites aegyptiaca fruits and Petroselinum sativum leaves aqueous extracts succeeded significantly in reducing the elevated mean plasma glucose level of the treated diabetic group in comparison with the DC group. In addition, the mean plasma insulin and L-PK levels of the BAETD and PSETD groups significantly increased with respect to the DC group. The diabetic rats that received Balanites aegyptiaca fruits aqueous extract demonstrated a more marked improvement in their mean plasma levels of glucose and insulin and L-PK level than Petroselinum sativum leaves aqueous extract.
(3) The comparison between the mean plasma TAC and MDA levels of the NC group and those of the BAETN and PSETN groups showed a non significant difference. The mean plasma TAC level of the DC group showed a high significant decrease while its mean plasma MDA level showed a high significant increase in comparison with the NC group. Oral administration of either Balanites aegyptiaca fruits aqueous extract or Petroselinum sativum leaves aqueous extract to the diabetic rats produced a significant increase in their mean plasma TAC levels and a significant decrease in their mean plasma MDA levels when compared with the diabetic control rats. Supplementation of Petroselinum sativum leaves aqueous extract to the diabetic rats resulted in a better improvement in their mean plasma TAC and MDA levels than Balanites aegyptiaca fruits aqueous extract.
(4) In the BAETN and PSETN groups, the mean weight of the pancreatic tissue and size of the islets of Langerhans were non significantly different from those of the NC group. The histopathological pictures of pancreas in the BAETN group and PSETN groups were similar to that of the NC group. On the other hand, a high significant decrement was found in the mean weight of the pancreatic tissue and size of pancreatic islets of the DC group when compared with the NC group. Severe degenerative and necrotic changes were observed in the islets cells of the DC group. In addition, the nuclei of the pancreatic cells showed pyknosis and karyolysis. Disappearance of some cells nuclei and presence of residues of the nuclei and destroyed cells were also seen. Following administration of Balanites aegyptiaca fruits and Petroselinum sativum leaves aqueous extract to the diabetic rats, both of the BAETD and PSETD groups exhibited a significant increment in the mean pancreatic tissue weight and the mean size of the islets of Langerhans as compared with the DC group. Most of the cells appeared normal and some of them were in the regenerative state in the BAETD group. While in the PSETD group, few degenerative and necrotic changes were still found in the pancreatic islets cells. The pancreatic tissue in the BAETD group showed a more marked improvement than that observed with the PSETD group.
Summary
Type 1 diabetes mellitus (T1DM) is a multifactorial autoimmune disease which is characterized by T-cell mediated destruction of the insulin secreting β cells in the pancreatic islets. The destructive process leads to severe insulin depletion that results in hyperglycemia because of hepatic overproduction of glucose by glycogenolysis and gluconeogenesis and decreased cellular uptake of glucose from circulation.
T1DM remains a major global health problem especially in the developing countries in spite of the availability of many antidiabetic drugs because they have limited efficacy and certain adverse effects. This leads to an increased demand of research on antidiabetic natural products such as medicinal plants that produce minimal or no side effects. Unfortunately, phytotherapy is not yet included in the evidence-based medicine, especially with respect to diabetes mellitus therapy. Studies to reveal the mode of action of potential antidiabetic plants will definitely give scientific and systematic approach for the use of these plants as hypoglycemic agents.
Streptozotocin (STZ) is frequently used to induce experimental T1DM and its diabetic action results from its highly specific cytotoxic action on β cells by increased production of oxygen free radicals that results in oxidative stress.
Balanites aegyptiaca is a widely distributed African plant of medicinal interest. In Egyptian folk medicine, its fruit mesocarp is commonly used as an oral antidiabetic drug. Petroselinum sativum is a cultivated variety of parsley and traditionally was used as carminative, abortifacient and anti-hypertensive agents. Until now, no data in the literature could be found about the antioxidant influences of Balanites aegyptiaca extracts in normal and diabetes-induced experimental models or its possible hypoglycemic effects on normal animals. Although there are few published articles about the antidiabetic effects of Petroselinum crispum extracts on the diabetic and normal animals and also their antioxidant effects on diabetic animals, but no work has been done to study the antidiabetic and antioxidant properties of Petroselinum sativum extracts in the diabetic or normal animals. For these reasons, the current study has been undertaken to examine the possible antidiabetic and antioxidant effects of Balanites aegyptiaca fruits and Petroselinum sativum leaves aqueous extracts in STZ-induced diabetic (hyperglycemic) and normal (normoglycemic) rats in a hop to transmit the results for the human use.
To achieve these objectives, the influences of both extracts on body weight (BW), and on plasma glucose, insulin, total antioxidant capacity (TAC) and malondialdehyde (MDA) levels, and on liver-pyruvate kinase (L-PK) level were assessed. Furthermore, the weight and the histopathological changes of pancreas were studied, and the pancreatic islet size was measured in the different experimental groups.
After preparation of the extracts and induction of diabetes using STZ, 60 adult male rats in this study were divided into 6 groups, 10 rats each, in two experiments having 45 days duration. Experiment 1 was planed to assess the possible hypoglycemic and antioxidant effects of Balanites aegyptiaca fruits and Petroselinum sativum leaves aqueous extracts on normal rats and it included normal control (NC), Balanites aegyptiaca extract-treated normal (BAETN) and Petroselinum sativum extract-treated normal (PSETN) groups. While experiment 2 was constructed to estimate the possible antidiabetic and antioxidant effects of Balanites aegyptiaca fruits and Petroselinum sativum leaves aqueous extracts on STZ-induced diabetic rats, and it included diabetic control (DC), Balanites aegyptiaca extract-treated diabetic (BAETD) and Petroselinum sativum extract-treated diabetic (PSETD) groups. At the end of the experiments, the live BW of the overnight-fasted rats was recorded and the blood samples were collected followed by separation of the plasma. After that, the rats were sacrificed and the liver tissue was excised, rinsed in ice-cold physiological saline and then homogenized. The plasma glucose, TAC and MDA levels and L-PK level were measured colorimetrically using spectrophotometer, while the plasma insulin level was measured by enzyme-linked immunosorbant assay (ELISA) reader using specific ELISA kit.
After scarification and evisceration of the rats, the pancreas was taken from each animal, rinsed in normal saline and dried, followed by measurement of pancreas weight for each animal. Pancreas weight per 100 gm BW was calculated in the various experimental groups to make a functional comparison of weight loss and gain. A pancreas biopsy specimen from each rat was obtained and prepared for staining with hematoxylin and eosin and then examined under light microscope. After that, the sizes of 100 islets were measured in each group and the mean size was calculated.
This study showed the following results:
(1) The mean final BW of the BAETN and PSETN groups was slightly higher than that of the NC group, but the increase was non significant. A high significant decrement in the mean final BW of the DC group was observed in comparison with the NC group. The mean final BW of the BAETD and PSETD groups were significantly greater than that of the DC group. In the BAETD group, the mean final BW exhibited more obvious enhancement than that detected in the PSETD group.
(2) A non significance difference was found between the mean plasma levels of glucose and insulin and L-PK level of the NC group versus those of the BAETN and PSETN groups. The DC group was characterized by a high significant increment in its mean plasma glucose level and a high significant decrement in its mean plasma insulin and L-PK levels as compared with the NC group. Balanites aegyptiaca fruits and Petroselinum sativum leaves aqueous extracts succeeded significantly in reducing the elevated mean plasma glucose level of the treated diabetic group in comparison with the DC group. In addition, the mean plasma insulin and L-PK levels of the BAETD and PSETD groups significantly increased with respect to the DC group. The diabetic rats that received Balanites aegyptiaca fruits aqueous extract demonstrated a more marked improvement in their mean plasma levels of glucose and insulin and L-PK level than Petroselinum sativum leaves aqueous extract.
(3) The comparison between the mean plasma TAC and MDA levels of the NC group and those of the BAETN and PSETN groups showed a non significant difference. The mean plasma TAC level of the DC group showed a high significant decrease while its mean plasma MDA level showed a high significant increase in comparison with the NC group. Oral administration of either Balanites aegyptiaca fruits aqueous extract or Petroselinum sativum leaves aqueous extract to the diabetic rats produced a significant increase in their mean plasma TAC levels and a significant decrease in their mean plasma MDA levels when compared with the diabetic control rats. Supplementation of Petroselinum sativum leaves aqueous extract to the diabetic rats resulted in a better improvement in their mean plasma TAC and MDA levels than Balanites aegyptiaca fruits aqueous extract.
(4) In the BAETN and PSETN groups, the mean weight of the pancreatic tissue and size of the islets of Langerhans were non significantly different from those of the NC group. The histopathological pictures of pancreas in the BAETN group and PSETN groups were similar to that of the NC group. On the other hand, a high significant decrement was found in the mean weight of the pancreatic tissue and size of pancreatic islets of the DC group when compared with the NC group. Severe degenerative and necrotic changes were observed in the islets cells of the DC group. In addition, the nuclei of the pancreatic cells showed pyknosis and karyolysis. Disappearance of some cells nuclei and presence of residues of the nuclei and destroyed cells were also seen. Following administration of Balanites aegyptiaca fruits and Petroselinum sativum leaves aqueous extract to the diabetic rats, both of the BAETD and PSETD groups exhibited a significant increment in the mean pancreatic tissue weight and the mean size of the islets of Langerhans as compared with the DC group. Most of the cells appeared normal and some of them were in the regenerative state in the BAETD group. While in the PSETD group, few degenerative and necrotic changes were still found in the pancreatic islets cells. The pancreatic tissue in the BAETD group showed a more marked improvement than that observed with the PSETD group.