الفهرس | Only 14 pages are availabe for public view |
Abstract Diabetes mellitus (DM) is one of the most critical health problems in the 21st century in both developed and developing countries. The international diabetes federation reported that the incidence of diabetes has increased from 4.7% at 1980 to 8.5% at 2016 in the adult population. Egypt is ranked the eighth in the world in terms of diabetes. There are three main types of DM; type 1 (T1DM) which accounts for 5-10 % of diabetic patients and in which patients must be supplied with external insulin. The second type is called T2DM which accounts for about 90% of all diabetics and is characterized by insulin resistance. Gestational diabetes usually occurs during pregnancy due to the antagonistic effect of placental hormones to insulin and usually disappears after labor. Insulin plays a critical rule in glucose homeostasis, for normal insulin signal, insulin should bind to its receptor and activates two important proteins called insulin receptor substrate 1 and 2 (IRS1 and IRS2). T2DM is characterized by insulin resistance as insulin failed to bind its receptor to induce activation of tyrosine kinase activity of the intracellular subunit of its receptor and therefore the sensitivity of target tissues to insulin decreases. Several hepatokines are involved in glucose and lipid metabolism. Impairment of such essential hepatic cytokines may lead to impaired insulin sensitivity and increased hepatic glucose production and lipogenesis Morbidity and mortality due to diabetes cause a heavy economic stress on health care system so that there is a strong need to create new strategies and drugs for controlling DM. Medicinal plants considered a natural and safe source for active compounds used for treatment of many diseases since many decades. Pterocarpus santalinus is one of the medicinal plants with an anti-diabetic effect. In the current study, T2DM was established using a single dose of 65mg/kg of streptozotocin (STZ). Fourty two male rats were divided into seven groups of six rats each as follows: -The first group was the control and sacrificed after 4 weeks. -The second group received the aqueous plant extract (250mg/kg) orally and daily for three weeks. -The third group (STZ1) was intraperitoneally (i.p) injected with a single dose of 65mg/kg of streptozotocin (STZ) and sacrificed after four weeks. -The fourth group was injected with a single dose of STZ then after one week it was treated orally with the aqueous plant extract daily for three weeks, then sacrificed. -The fifth group was injected with a single dose of STZ then after one week it was treated orally with 3 mg/kg of reference drug (glustin) daily for three weeks, then sacrificed. -The sixth group (STZ2) received standard food pellets for three weeks then injected with a single dose of STZ then sacrificed after one week.-The seventh group was administered with the plant extract daily for three weeks then injected with a single dose of STZ then sacrificed after one week. The effects of both the plant extract and STZ were studied by measuring the body weight change, FBS, insulin, HbA1c, HOMA-IR, liver function, kidney function and lipid profile. The mRNA expression of fetuin-A, SIRT-1, c-JNK and IRS-1 was measured by qRT-PCR. Histopathological examination was performed for sections of pancreas. In addition, the HPLC analysis of plant extract was performed. Streptozotocin was able to induce T2DM. The levels of glucose, HOMA-IR and HbA1c were elevated while insulin level was significantly decreased. Liver enzymes were not affected by STZ. Urea level was elevated by STZ while creatinine was unchanged. Lipid profile was not affected by STZ. STZ caused a down-regulation of mRNA expression of fetuin-A while both JNK and SIRT-1 were up-regulated. STZ did not cause any significant change in IRS-1 mRNA expression. The plant extract was able to ameliorate the deteriorations caused by STZ. When diabetic rats were treated with the extract, the levels of glucose, HOMA-IR and HbA1c were decreased and insulin was elevated. The plant extract caused a significant amelioration of both creatinine and urea levels. The plant extract caused a down-regulation of mRNA expression of JNK and SIRT-1 while mRNA expression of IRS-1 was upregulated. Glustin did not ameliorate the deteriorations caused by STZ and failed to improve insulin resistance. Glustin caused a significant decrease in AST activity and LDL-chol level. Treating diabetic rats with glustin caused up-regulation of fetuin-A mRNA expression while both SIRT-1 and JNK were down-regulated. The plant extract did not protect against induction and progression of DM. |