The Effects of stingless bee (Tetragonula biroi) honey on streptozotocin-induced diabetes mellitus in rats

Diabetes mellitus (DM) is a metabolic disease characterised by chronic hyperglycaemia with impaired carbohydrate, fat and protein metabolism caused by defects in insulin secretion or action. Based on our previous research, stingless bee honey (SLBH) from Tetragonula biroi and T. laeviceps can inhibit alpha-glucosidase activities. Therefore, the aim of the present study was to determine the effects of daily oral administration of SLBH on body weight (BW) and fasting blood glucose (FBG) levels of male rats with streptozotocin (STZ)-induced DM. Thirty-six male Sprague Dawley rats were divided into six groups of six rats each. One group of normal non-diabetic rats served as a positive control. The diabetic groups were intraperitoneally (i.p.) injected with STZ (50 mg/kg BW) for induction of DM and divided into five equal subgroups of six animals each: an untreated group as a negative control; a group treated with 0.6 mg/kg BW of glibenclamide as a positive control and three SLBN treatment groups that had daily oral administration of 0.5, 1.0 or 2.0 g/kg BW, respectively, for 35 days. The results showed that SLBH significantly reduced loss of BW in diabetic rats. FBG levels in diabetic rat blood, collected from the tail, were measured using Accu-Chek test strips. The FBG levels in diabetic rats that have oral administered intake with glibenclamide and SLBH were stable. There were no changes in serum FBG levels in SLBH-treated diabetic rats for 35 days. Pancreatic histopathology results from all groups showed no abnormalities or tissue damage in either diabetic or non-diabetic rats. The results of this study show that administration of SLBH reduced BW loss or improved BW of rats with STZ-induced DM. Meanwhile, the reduction in loss of BW that occurred in diabetic rats after 35 days of SLBH administration was the result of reduced formation of fats and proteins, which are broken down into energy. Further research is needed to determine the antidiabetic effects of honey from other stingless honeybee species.     

Cathinone: An alkaloid of Catha edulis (Khat) exacerbated hyperglycemia in diabetes-induced rats

Cathinone, the main bioactive alkaloid of Catha edulis (khat), slightly increased the blood sugar levels of healthy animals, while its effect on blood sugar levels of diabetic animals has not yet been reported. This study investigated the in vitro inhibition of cathinone on α-amylase and α-glucosidase as well as its in vivo glycemic effects in diabetes-induced rats. Rats were fed on a high fat diet for five weeks, which then intraperitoneally injected with streptozotocin (30 mg/kg). Diabetic rats were distributed randomly into diabetic control (DC, n = 5), 10 mg/kg glibenclamide-treated group (DG, n = 5), and 1.6 mg/kg cathinone-treated group (CAD, n = 5). Additional healthy untreated rats (n = 5) served as a nondiabetic negative control group. Throughout the experiment, fasting blood sugar (FBS), caloric intake and body weight were recorded weekly. By the 28th day of treatment, rats were euthanized to obtain blood samples and pancreases. The results demonstrated that cathinone exerted a significantly less potent in vitro inhibition than α-acarbose against α-amylase and α-glucosidase. As compared to diabetic control group, cathinone significantly increased FBS of diabetic rats, while insulin levels of diabetic rats significantly decreased. In conclusion, cathinone was unable to induce a substantial in vitro inhibition on α-amylase and α-glucosidase, while it exacerbated the hyperglycemia of diabetes-induced rats.     

Ellagic acid improved diabetes mellitus-induced testicular damage and sperm abnormalities by activation of Nrf2

Diabetes mellitus induces testicular damage, increases sperm abnormalities, and impairs reproductive dysfunction due to induction of endocrine disturbance and testicular oxidative stress. This study evaluated the reproductive protective effect of ellagic acid (EA) against testicular damage and abnormalities in sperm parameters in Streptozotocin (STZ)-induced diabetic rats (T1DM) and examined some possible mechanisms of protection. Adult male rats were segregated into 5 groups (n = 12 rat/each) as control, control + EA (50 mg/kg/day), T1DM, T1DM + EA, and T1DM + EA + brusatol (an Nrf-2 inhibitor) (2 mg/twice/week). All treatments were conducted for 12 weeks, daily. EA preserved the structure of the seminiferous tubules, prevented the reduction in sperm count, motility, and viability, reduced sperm abnormalities, and downregulated testicular levels of cleaved caspase-3 and Bax in diabetic rats. In the control and diabetic rats, EA significantly increased the circulatory levels of testosterone, reduced serum levels of FSH and LH, and upregulated Bcl-2 and all steroidogenic genes (StAr, 3β-HSD1, and 11β-HSD1). Besides, it reduced levels of ROS and MDA but increased levels of GSH and MnSOD and the transactivation of Nrf2. All these biochemical alterations induced by EA were associated with increased activity and nuclear accumulation of Nrf2. However, all these effects afforded by EA were weakened in the presence of brusatol. In conclusion, EA could be an effective therapy to alleviated DM-induced reproductive toxicity and dysfunction in rats by a potent antioxidant potential mediated by the upregulation of Nrf2.     

Melatonin relieves diabetic complications and regenerates pancreatic beta cells by the reduction in NF-kB expression in streptozotocin induced diabetic rats

Melatonin, a pleiotropic hormone, has many regulatory effects on the circadian and seasonal rhythms, sleep and body immune system. It is used in the treatment of blind circadian rhythm sleep disorders, delayed sleep phase and insomnia. It is a potent antioxidant, anti-inflammatory, free radical scavenger, helpful in fighting infectious disease and cancer treatment. Decreased level of circulating melatonin was associated with an increased blood glucose level, losing the anti-oxidant protection and anti-inflammatory responses. We aimed to evaluate the effect of melatonin administration, in streptozotocin (STZ) induced diabetic rats, on blood glucose level and pancreatic beta (β) cells. Diabetes mellitus was induced in Sprague dawley male rats by the intravenous (i.v) injection of 65 mg/kg of STZ. Diabetic rats received melatonin at a dose of 10 mg/kg daily for 8 weeks by oral routes. The results showed, after 8 weeks of melatonin administration, a reduction in: 1- fasting blood glucose (FBG) and fructosamine (FTA) levels, 2- kidney and liver function parameters, 3- levels of serum triglycerides, cholesterol and LDL-C, 4- malondialdehyde (MDA), 5- NF-κB expression in treated group, 6- pro-inflammatory cytokines (IL-1β and IL-12) and immunoglobulins (IgA, IgE and IgG). Furthermore, an elevation in insulin secretion was noticed in melatonin treated group that indicated β cells regeneration. Therefore, melatonin administration, in STZ induced diabetic rats; reduced hyperglycemia, hyperlipidemia and oxidative stress. Melatonin acted as an anti-inflammatory agent that reduced pro-inflammatory cytokines (IL-1β and IL-12) and oxidative stress biomarkers (MDA). Melatonin succeeded in protecting β cells under severe inflammatory situations, which was apparent by the regeneration of islets of Langerhans in treated diabetic rats. Moreover, these results can open a gate for diabetes management and treatment.     

Marantodes pumilum Var Alata (Kacip Fatimah) ameliorates derangement in RANK/RANKL/OPG pathway and reduces inflammation and oxidative stress in the bone of estrogen-deficient female rats with type-2 diabetes

BackgroundM. pumilum has been claimed to protect the bone against the adverse effect of estrogen deficiency. Additionally, it also exhibits anti-diabetic activity. In view of these, this study aims to identify the mechanisms underlying the bone protective effect of M. pumilum in the presence of both estrogen deficiency and diabetes mellitus (DM).MethodsOvariectomized, diabetic female rats were given M. pumilum leave aqueous extract (MPLA) (50 and 100 mg/kg/day), estrogen, glibenclamide and estrogen plus glibenclamide for 28 consecutive days. At the end of the treatment, fasting blood glucose (FBG), serum insulin, Ca²⁺, PO₄³⁻ and bone alkaline phosphatase (BALP) levels were measured. Rats were sacrificed and femur bones were harvested for determination of expression level and distribution of RANK, RANKL, OPG and oxidative stress and inflammatory proteins by molecular biological techniques.Results100 mg/kg/day MPLA treatment decreased the FBG and BALP levels but increased the serum insulin, Ca²⁺ and PO₄³⁻ levels in estrogen deficient, diabetic rats. Expression and distribution of RANKL, NF-κB p65, IKKβ, IL-6, IL-1β and Keap-1 decreased however expression and distribution of RANK, OPG, BMP-2, Type-1 collagen, Runx2, TRAF6, Nrf2, NQO-1, HO-1, SOD and CAT increased in the bone of estrogen deficient, diabetic rats which received 100 mg/kg/day MPLA with greater effects than estrogen-only, glibenclamide-only and estrogen plus glibenclamide treatments.ConclusionMPLA helps to overcome the adverse effect of estrogen deficiency and DM on the bone and thus this herb could potentially be used for the treatment and prevention of osteoporosis in postmenopausal women with diabetes.     

Cardioprotective effect of propranolol on diabetes-induced altered intracellular Ca2+ signaling in rat

We have previously shown that chronic treatment with propranolol had beneficial effects on heart function in rats during increasing-age in a gender-dependent manner. Herein, we hypothesize that propranolol would improve cardiac function in diabetic cardiomyopathy and investigated the benefits of chronic oral administration of propranolol on the parameters of Ca²⁺ signaling in the heart of streptozotocin-diabetic rats. Male diabetic rats received propranolol (25 mg/kg, daily) for 12 weeks, 1 week after diabetes induction. Treatment of the diabetic rats with propranolol did not produce a hypoglycaemic effect whereas it attenuated the increased cell size. Basal and β-agonist response levels of left ventricular developed pressure were significantly higher in propranolol-treated diabetic rats relative to untreated diabetics while left ventricular end diastolic pressure of the treated diabetics was comparable to the controls. Propranolol treatment normalized also the prolongation of the action potential in papillary muscles from the diabetic rat hearts. This treatment attenuated the parameters of Ca²⁺ transients, depressed Ca²⁺ loading of the sarcoplasmic reticulum, and of the basal intracellular Ca²⁺ level of diabetic cardiomyocytes. Furthermore, Western blot data indicated that the diabetes-induced alterations in the cardiac ryanodine receptor Ca²⁺ release channel’s hyperphosphorylation decreased the FKBP12.6 protein level. Also, the high phosphorylated levels of PKA and CaMKII were prevented with propranolol treatment. Chronic treatment with propranolol seems to prevent diabetes-related changes in heart function by controlling intracellular Ca²⁺ signaling and preventing the development of left ventricular remodeling in diabetic cardiomyopathy.     

AD-MSCs and BM-MSCs Ameliorating Effects on The Metabolic and Hepato-renal Abnormalities in Type 1 Diabetic Rats

Diabetes mellitus (DM) is one of the most serious threats in the 21th century throughout the human population that needs to be addressed cautiously. Nowadays, stem cell injection is considered among the most promising protocols for DM therapy; owing to its marked tissues and organs repair capability. Therefore, our 4 weeks study was undertaken to elucidate the probable beneficial effects of two types of adult mesenchymal stem cells (MSCs) on metabolism disturbance and some tissue function defects in diabetic rats. Animals were classified into 4 groups; the control group, the diabetic group, the diabetic group received a single dose of adipose tissue-derived MSCs and the diabetic group received a single dose of bone marrow-derived MSCs. Herein, both MSCs treated groups markedly reduced hyperglycemia resulting from diabetes induction via lowering serum glucose and rising insulin and C-peptide levels, compared to the diabetic group. Moreover, the increased lipid fractions levels were reverted back to near normal values as a consequence to MSCs injection compared to the diabetic untreated rats. Furthermore, both MSCs types were found to have hepato-renal protective effects indicated through the decreased serum levels of both liver and kidney functions markers in the treated diabetic rats. Taken together, our results highlighted the therapeutic benefits of both MSCs types in alleviating metabolic anomalies and hepato-renal diabetic complications.     

Differential effects of treadmill exercise in early and chronic diabetic stages on parvalbumin immunoreactivity in the hippocampus of a rat model of type 2 diabetes

In the present study, we investigated the effects of treadmill exercise in early and chronic diabetic stages on parvalbumin (PV) immunoreactivity in the subgranular zone of the dentate gyrus of Zucker diabetic fatty (ZDF) and its lean control rats (ZLC). To investigate the effects, ZLC and ZDF rats at 6 or 23 weeks of age were put on a treadmill with or without running for 1 h/day/5 consecutive days at 16–22 m/min for 5 weeks or 12–16 m/min for 7 weeks, respectively. Physical exercise in pre-diabetic rats prevented onset of diabetes, while exercise in rats at chronic diabetic stage significantly reduced blood glucose levels. In addition, physical exercise in the pre-diabetic rats significantly increased PV immunoreactive fibers in the strata oriens and radiatum of the CA1-3 region and in the polymorphic and molecular layers of the dentate gyrus compared to that in sedentary controls. However, in rats at chronic stages, PV immunoreactivity was slightly increased in the CA1-3 region as well as in the dentate gyrus compared to that in the sedentary controls. These results suggest that physical exercise has differential effects on blood glucose levels and PV immunoreactivity according to diabetic stages. Early exercise improves diabetic phenotype and PV immunoreactive fibers in the rat hippocampus.     

Astragaloside IV ameliorates renal injury in streptozotocin-induced diabetic rats through inhibiting NF-κB-mediated inflammatory genes expression

Accumulating evidence suggests that inflammatory processes are involved in the development of diabetic nephropathy (DN). However, there are no effective interventions for inflammation in the diabetic kidneys. Here, we tested the hypothesis that Astragaloside IV(AS-IV), a novel saponin purified from Astragalus membranaceus (Fisch) Bge, ameliorates DN in streptozotocin (STZ)-induced diabetic rats through anti-inflammatory mechanisms. Diabetes was induced with STZ (65 mg/kg) by intraperitoneal injection in rats. Two weeks after STZ injection, rats were divided into three groups (n = 8/each group), namely, diabetic rats, diabetic rats treated with AS-IV at 5 and 10 mg kg^?1 d^?1, p.o., for 8 weeks. The normal rats were chosen as nondiabetic control group (n = 8). The rats were sacrificed 10 weeks after induction of diabetes. AS-IV ameliorated albuminuria, renal histopathology and podocyte foot process effacement in diabetic rats. Renal NF-κB activity, as wells as protein and mRNA expression were increased in diabetic kidneys, accompanied by an increase in mRNA expression and protein content of TNF-α, MCP-1 and ICAM-1 in kidney tissues. The α₁-chain type IV collagen mRNA was elevated in the kidneys of diabetic rats. All of these abnormalities were partially restored by AS-IV. AS-IV also decreased the serum levels of TNF-α, MCP-1 and ICAM-1 in diabetic rats. These findings suggest that AS-IV, a novel anti-inflammatory agent, attenuated DN in rats through inhibiting NF-κB mediated inflammatory genes expression.     

The effect of melatonin on glycoprotein levels and oxidative liver injury in experimental diabetes

In this present study, the duration of melatonin (Mel) administered to diabetic rats was prolonged so as to examine its effects on the biochemical liver parameters of diabetic rats. In the experiment, Male Sprague Dawley rats were divided randomly into five groups; the control, diabetic + Mel, diabetic, diabetic + insulin, and diabetic + Mel + insulin. Diabetes mellitus was induced by administration of a single dose of streptozotocin (60 mg/kg) intraperitoneally and rats were given vehicle as a solvent for Mel every day for 12 weeks. In the diabetic + Mel group, diabetic rats were administered Mel (10 mg/kg/day) for 12 weeks to treat diabetes. The diabetic + insulin group were diabetic rats given insulin (6 U/kg) subcutaneously for 12 weeks. The diabetic + Mel + insulin rats received insulin and Mel at the same dose and time. At the end of the experiment, the animals were decapitated and liver tissues were taken. The protective effect of Mel on liver tissue of diabetic rats was investigated, total antioxidant status, total oxidant status, reactive oxygen species, oxidative stress index, adenosine deaminase, xanthine oxidase, paraoxonase 1, sodium/potassium ATPase, myeloperoxidase, γ-glutamyl transferase, sorbitol dehydrogenase, tumor necrosis factor-alpha, homocysteine, nitric oxide, glucose-6-phosphate dehydrogenase, and glycoprotein levels were determined in liver tissues. Treatment with Mel and/or insulin has been found to have a protective effect on biochemical parameters. The results showed that administration of Mel to diabetic rats prevented the distortion of the studied biochemical parameters of liver tissues.     

Anti-hyperglycemic and anti-oxidative effect of aqueous extract of Momordica charantia pulp and Trigonella foenum graecum seed in alloxan-induced diabetic rats

Diabetes is an oxidative stress disorder and oxidative damage to tissues such as heart, kidney, liver and other organs may be a contributory factor to several diabetic complications. Momordica charantia (family: Cucurbitaceae) and Trigonella foenum graecum (family: Fabaceae) are used traditionally in Indian folk medicine to manage diabetes mellitus. In the present study, the anti-hyperglycemic and anti-oxidative potential of aqueous extracts of M. charantia pulp and seed powder of T. foenum graecum were assessed in alloxan (150 mg/kg body weight) induced diabetic rats. Alloxan treatment to the rats could induce diabetes as the fasting blood glucose (FBG) levels were > 280 mg/dl. Treatment of diabetic rats for 30 days with M. charantia and T. foenum graecum could significantly (p < 0.001) improve the FBG levels to near normal glucose levels. Antioxidant activities (superoxide dismutase, catalase, reduced glutathione content and glutathione-s-transferase) and lipid peroxidation levels were measured in heart, kidney and liver tissues of normal, diabetic and experimental animals (diabetics + treatment). TBARS levels were significantly (p < 0.001) higher and anti-oxidative activities were found low in diabetic group, as compared to the control group. Significant (p < 0.001) improvement in both the TBARS levels and antioxidant activities were observed when M. charantia and T. foenum graecum were given to diabetic rats. Our results clearly demonstrate that M. charantia and T. foenum graecum are not only useful in controlling the blood glucose levels, but also have antioxidant potential to protect vital organs such as heart and kidney against damage caused due to diabetes induced oxidative stress.     

Protective effect of atorvastatin on oxidative stress in streptozotocin‐induced diabetic rats independently their lipid‐lowering effects

In the present study, we investigate the effects of atorvastatin on the lipid profile, oxidative stress, and liver enzyme markers, and its protective activity against diabetic complications, in streptozotocin (STZ)‐induced diabetic rats. Fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and high‐density lipoprotein (HDL) levels, as well as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzyme activities, were measured 7 weeks after the administration of STZ and atorvastatin. Thiobarbituric acid reactive substances (TBARS), non‐protein associated sulfhydryl (NP‐SH), total sulfhydryl (T‐SH), and nitric oxide (NO) levels were measured to evaluate oxidative stress. Atorvastatin was found to inhibit ALT and AST activities and to reduce FBG levels in rats with STZ‐induced diabetes. Moreover, atorvastatin treatment significantly reduced lipid peroxidation in kidney, heart, and eye tissues (P < 0.001, for all), and resulted in a significant increase in NP‐SH levels in brain tissues (P < 0.001). Total NO and nitrate levels increased significantly after atorvastatin treatment (P < 0.01). Our results revealed that atorvastatin has a protective effect against STZ‐induced oxidative damage by reducing TBARS levels and increasing NP‐SH levels, has a hepatoprotective effect by decreasing ALT and AST activities. It also shows the antihyperglycemic activity by lowering FBG levels.     

Effect of Treadmill Exercise on Blood Glucose,Serum Corticosterone Levels and Glucocorticoid Receptor Immunoreactivity in the Hippocampus in Chronic Diabetic Rats

Abnormal excess of glucocorticoid is one of feature characteristics in type 2 diabetes. In the present study, we investigated the effect of treadmill exercise at chronic diabetic stages on glucocorticoid receptor (GR) immunoreactivity in the hippocampal CA1 region and dentate gyrus, which are very vulnerable to diabetes. For this study, we used Zucker diabetic fatty (ZDF) rats and Zucker lean control (ZLC) rats. Twenty-three-week-old ZLC and ZDF rats were put on the treadmill with or without running for 7 weeks and sacrificed at 30 weeks of age. Treadmill exercise significantly decreased diabetes-induced blood glucose and serum corticosteroid levels although they did not drop to control levels. In sedentary ZLC rats, GR immunoreactivity was detected in pyramidal cells of the CA1 region as well as in granule cells of the dentate gyrus. In the sedentary ZDF rats, GR immunoreactivity was significantly increased in these regions. However, treadmill exercise significantly decreased GR immunoreactivity in these regions. These results indicate that treadmill exercise in chronic diabetic rats significantly decreased GR immunoreactivity in the hippocampal CA1 region and dentate gyrus, although blood glucose and serum corticosteroid levels did not fully recover to normal state.     

Central visfatin potentiates glucose-stimulated insulin secretion and β-cell mass without increasing serum visfatin levels in diabetic rats

IntroductionOur previous study revealed that plasma visfatin levels were lower in pregnant women with gestational diabetes (GDM) than non-GDM independent of prepreganacy BMI. We examined whether central visfatin modulates energy and glucose homeostasis via altering insulin resistance, insulin secretion or islet morphometry in diabetic rats.MethodsPartial pancreatectomized, type 2 diabetic, rats were interacerbroventricularly infused with visfatin (100 ng/rat/day, Px-VIS), visfatin + visfatin antagonist, CHS-828 (100 μg/rat/day, Px-VIS-ANT), or saline (control, Px-Saline) via osmotic pump, respectively, for 4 weeks.ResultsCentral visfatin improved insulin signaling (pAkt → pFOXO-1) but not pSTAT3 in the hypothalamus. Central visfatin did not alter serum visfatin levels in diabetic rats whereas the levels were higher in non-diabetic rats than diabetic rats. Body weight at the 2nd week was lowered in the Px-VIS group due to decreased food intake in the first two weeks compared to the Px-Saline group and energy expenditure was not significantly different among the treatment groups of diabetic rats. Visfatin antagonist treatment nullified the central visfatin effect. Px-VIS increased whole body glucose disposal rates in euglycemic hyperinsulinemic clamp compared to Px-Saline and lowered hepatic glucose output, whereas Px-VIS-ANT blocked the visfatin effect on insulin resistance (P < 0.05). In hyperglycemic clamp study, the area under the curve of insulin in first and second phase were significantly higher in the Px-VIS group than the Px-Saline group without modifying insulin sensitivity at the hyperglycemic state, whereas the increase in serum insulin levels was blocked in the Px-VIS-ANT group. Central visfatin also increased β-cell mass by increasing β-cell proliferation.ConclusionsCentral visfatin improved glucose homeostasis by increasing insulin secretion and insulin sensitivity at euglycemia through the hypothalamus in diabetic rats. Therefore, visfatin is a positive modulator of glucose homeostasis by delivering the hypothalamic signals into the peripheries.     

Specific functioning of Cav3.2 T-type calcium and TRPV1 channels under different types of STZ-diabetic neuropathy

Streptozotocin (STZ)-induced type 1 diabetes in rats leads to the development of peripheral diabetic neuropathy (PDN) manifested as thermal hyperalgesia at early stages (4th week) followed by hypoalgesia after 8 weeks of diabetes development. Here we found that 6–7 week STZ-diabetic rats developed either thermal hyper- (18%), hypo- (25%) or normalgesic (57%) types of PDN. These developmentally similar diabetic rats were studied in order to analyze mechanisms potentially underlying different thermal nociception. The proportion of IB4-positive capsaicin-sensitive small DRG neurons, strongly involved in thermal nociception, was not altered under different types of PDN implying differential changes at cellular and molecular level. We further focused on properties of T-type calcium and TRPV1 channels, which are known to be involved in Ca^2 + signaling and pathological nociception. Indeed, TRPV1-mediated signaling in these neurons was downregulated under hypo- and normalgesia and upregulated under hyperalgesia. A complex interplay between diabetes-induced changes in functional expression of Cav3.2 T-type calcium channels and depolarizing shift of their steady-state inactivation resulted in upregulation of these channels under hyper- and normalgesia and their downregulation under hypoalgesia. As a result, T-type window current was increased by several times under hyperalgesia partially underlying the increased resting [Ca^2 +]_i observed in the hyperalgesic rats. At the same time Cav3.2-dependent Ca^2 + signaling was upregulated in all types of PDN. These findings indicate that alterations in functioning of Cav3.2 T-type and TRPV1 channels, specific for each type of PDN, may underlie the variety of pain syndromes induced by type 1 diabetes.     

高热量高蛋白饮食诱导GK大鼠糖尿病肾病模型的建立

目的运用高热量高蛋白饮食诱导GK大鼠2型糖尿病肾病模型的建立,并探讨其可能的作用机制。方法 28周龄GK大鼠24只,随机分成对照组、模型组,每组各12只,模型组给予高热量高蛋白饮食,对照组给予正常饮食,共8周。于第0、4、8周观察24 h尿微量白蛋白、24 h尿蛋白、尿肌酐、尿微量白蛋白/尿肌酐比值水平;于第0、8周观察空腹血糖和血清肌酐、尿素氮、总胆固醇、甘油三脂、一氧化氮水平;实验结束时取双肾称重并计算肾肥大指数,取肾组织观察病理形态学变化,检测肾组织钠钾ATP酶活性。结果与对照组比,模型组大鼠24 h尿微量白蛋白、24 h尿蛋白、尿微量白蛋白/尿肌酐比值、空腹血糖、总胆固醇、甘油三脂、一氧化氮、肾肥大指数水平和肾组织钠钾ATP酶活性显著提高,模型组肾小球体积增大,系膜基质增生,基底膜增厚明显。结论运用高热量高蛋白饮食诱导GK大鼠可成功建立2型糖尿病肾病模型。血糖血脂的上升是糖尿病肾病形成的重要因素,同时钠钾ATP酶活性增强进一步损伤肾小管功能,一氧化氮升高促使肾小球高灌注、高滤过,也是加速GK大鼠肾病形成的原因。     

Changes in hypothalamic noradrenaline and 5-hydroxytryptamine levels during the development of warm- and cold-adaptation in the rat

Hypothalamic 5-hydroxytryptamine (5-HT) and noradrenaline (NA) as well as plasma corticosterone levels were studied in male rats after 1, 2, 4 and 6 weeks of exposure to 4--7 or 30--31 degrees C. An increase of the NA concentration and a decrease of the 5-HT level was observed after the first week in both cold and warm environment together with an increase of plasma corticosterone levels in both groups. NA, 5-HT and plasma corticosterone levels returned to normal in cold-exposed animals by the 6th week whereas in warm-acclimated rats NA and corticosterone levels regained their initial values and 5-HT concentrations remained low. Changes by the end of the first week of exposure may result from the thermal stress. The low 5-HT levels of warm-adapted animals at the end of the 6th week were probably secondary to the process of adaptation.     

Antioxidant icariside II combined with insulin restores erectile function in streptozotocin‐induced type 1 diabetic rats

Erectile dysfunction (ED) worsens in patients with diabetes mellitus (DM) despite good control of blood glucose level with insulin. Recent studies imply that diabetic vascular stresses (e.g. oxidative stress) persist in spite of glucose normalization, which is defined as metabolic memory. Studies suggest that the interaction between advanced glycation end products (AGEs) and their receptor (RAGE) mediates the development of metabolic memory. To investigate the effects of the antioxidant icariside II plus insulin on erectile function in streptozotocin (STZ)‐ induced type 1 diabetic rats. Fifty 8‐week‐old Sprague‐Dawley rats were randomly distributed into five groups: normal control, diabetic, insulin‐treated diabetic, icariside II‐treated diabetic, and insulin plus icariside II‐treated diabetic. Diabetes was induced by a single intraperitoneal injection of STZ. Eight weeks after induction of diabetes, icariside II was administered by gastric lavage once a day (5 mg/kg) for 6 weeks; and 2–6 units of intermediate‐acting insulin were given to maintain normal glycemia for 6 weeks. The main outcome measures were the ratio of intracavernous pressure (ICP) to mean arterial pressure (MAP); histology of penile endothelial cells and smooth muscle cells; neural nitric oxide synthase, AGEs and RAGE expression; malondialdehyde concentration; superoxide dismutase activity; and apoptosis index. Diabetic rats demonstrated a significantly lower ICP/MAP ratio, reduced penile endothelial cells, reduced smooth muscle cells, increased AGEs and RAGE, and increased apoptosis. Insulin and icariside II monotherapy partially restored erectile function and histological changes. However, the combination therapy group showed significantly better erectile parameters, cytological components and biochemistry, similar to those in the normal control group. These results suggest that, although insulin can effectively control glycemic levels, it does not completely alter the pathological changes in erectile tissues. Better efficacy could be expected with tight glycemic control plus the antioxidant icariside II. The proposed combination therapy might have the potential to eliminate metabolic memory by down‐regulating the AGEs‐RAGE‐oxidative stress axis.     

Nicorandil alleviates apoptosis in diabetic cardiomyopathy through PI3K/Akt pathway

Nicorandil exerts myocardial protection through its antihypoxia and antioxidant effects. Here, we investigated whether it plays an anti‐apoptotic role in diabetic cardiomyopathy. Sprague‐Dawley rats were fed with high‐fat diet; then single intraperitoneal injection of streptozotocin was performed. Rats with fasting blood glucose (FBG) higher than 11.1 mmol/L were selected as models. Eight weeks after the models were built, rats were treated with nicorandil (7.5 mg/kg day and 15 mg/kg day respectively) for 4 weeks. H9c2 cardiomyocytes were treated with nicorandil and then stimulated with high glucose (33.3 mmol/L). TUNEL assay and level of bcl‐2, bax and caspase‐3 were measured. 5‐HD was used to inhibit nicorandil. Also, PI3K inhibitor (Miltefosine) and mTOR inhibitor (rapamycin) were used to inhibit PI3K/Akt pathway. The results revealed that nicorandil (both 7.5 mg/kg day and 15mg/kg day) treatment can increase the level of NO in the serum and eNOS in the heart of diabetic rats compared with the untreated diabetic group. Nicorandil can also improve relieve cardiac dysfunction and reduce the level of apoptosis. In vitro experiments, nicorandil (100 µmol) can attenuate the level of apoptosis stimulated by high glucose significantly in H9C2 cardiomyocyte compared with the untreated group. The effect of nicorandil on apoptosis was blocked by 5‐HD, and it was accompanied with inhibition of the phosphorylation of PI3K, Akt, eNOS, and mTOR. After inhibition of PI3K/Akt pathway, the protective effect of nicorandil is restrained. These results verified that as a NO donor, nicorandil can also inhibit apoptosis in diabetic cardiomyopathy which is mediated by PI3K/Akt pathway.     

Effect of nano extracts of olea europaea leaves,ficus carica and liraglutide in lipidemic liver of type 2 diabetic rat model

The study aimed to evaluate the impact of Ficus carica mixture and Olea europaea leaf nano extracts, and liraglutide, on liver tissue and serum lipids in type 2 diabetic male albino rat model. Forty rats were divided equally into 4 groups were used. Group 1 was the non-diabetic control group. The animals in Groups 2–4 was injected intraperitoneally with a single dose of 60 mg/kg b.w. Streptozotocin to induce a diabetic rat model. Group 2 served as a positive control for diabetes. 0.02 mg/kg b.w./day of Liraglutide gave to groups 3 and 4 and 4.8 ng/ml × 10⁵ b.w./day of a mixture of the nano extracts, respectively. Eight weeks after treatment, the animals were sacrificed. Blood was collected for glucose analysis and serum low-density lipoprotein, high-density lipoprotein, total cholesterol, and triglycerides analysis, and the livers processed for histopathological examination. The elevated lipid profiles and blood glucose levels in diabetic group (Group 2) were significantly reduced (p < 0.001) following the administration of liraglutide and nano extracts in Groups 3 and 4. Progressive fatty acid changes were found in the liver sections, indicated by the deposition of various sizes of lipid droplets in most liver lobules, along with patchy hepatocyte necrosis. These pathological changes were ameliorated in the liraglutide- and nano-extract-treated rats. Treatment with the nano extracts resulted in significant power assays associated with recovery of hepatic histology and functional alterations, compared to liraglutide treatment.