Influence of rutin treatment on biochemical alterations in experimental diabetes

Dietary antioxidant compounds such as flavonoids may offer some protection against early-stage diabetes mellitus and its complications. Abnormalities in both glucose metabolism and lipid profile constitute one of the most common complications in diabetes mellitus. The present study aimed to evaluate the effect of rutin, through biochemical parameters, on experimental streptozotocin (STZ)-induced diabetes in rats. Male Wistar rats were divided into four groups: untreated controls (GI); normal rats receiving rutin (GII); untreated diabetics (GIII); diabetic rats receiving rutin (GIV). STZ was injected at a single dose of 60 mg kg^-1 to induce diabetes mellitus. The diabetes resulted in increased serum glucose, cholesterol, triacylglycerols and lipoproteins (LDL and VLDL-cholesterol) but decresed serum HDL-cholesterol and insulin. Rutin (50 mg kg^–1) reduced (p < 0.05) blood glucose and improved the lipid profile in STZ-induced diabetic rats. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) activities were significantly augmented in serum of STZ-diabetic rats, while these activities were diminished in hepatic and cardiac tissues compared with the control group. Rutin prevents changes in the activities of ALT, AST and LDH in the serum, liver and heart, indicating the protective effect of rutin against the hepatic and cardiac toxicity caused by STZ. Rutin was associated with markedly decreased hepatic and cardiac levels of tryacylglycerols and elevated glycogen. These results suggest that rutin can improve hyperglycemia and dyslipidemia while inhibiting the progression of liver and heart dysfunction in STZ-induced diabetic rats.     

Effects of bis(alpha-furancarboxylato)oxovanadium(IV) on non-diabetic and streptozotocin-diabetic rats

BACKGROUND: Bis(alpha-furancarboxylato)oxovanadium(IV) (BFOV), a new orally active anti-diabetic vanadium complex with organic agent, has been synthesized and characterized. The current study examined the stability in aqueous solution and effects of the complex on carbohydrate and lipid metabolism in non-diabetic and streptozotocin-induced diabetic rats. METHODS: Diabetic rats were induced by a single dose injection of streptozotocin (STZ, 50 mg/kg body weight, i.p.). The rats were randomly divided into non-diabetic (control, CON), diabetic (DM) and BFOV (0.2 mmol/kg body weight)-treated, diabetic-BFOV (0.1, 0.2 and 0.4 mmol/kg body weight) groups. All substances were given intragastrically to non-diabetic and STZ-induced diabetic rats for 4 weeks. Blood glucose concentration was monitored during administration and, at the end of experiment glycosylated hemoglobin, serum insulin, lipid concentrations and glycogen content were observed. RESULTS: Administration of BFOV to STZ-diabetic rats dose-dependently reduced blood glucose concentration when compared to diabetic rats (P<0.01), but it did not influence blood glucose in non-diabetic rats. Serum insulin concentrations were not increased in the BFOV-treated diabetic groups and, in contrast, significantly lowered in the 0.2 mmol/kg body weight BFOV-treated non-diabetic group at the end of experiment. Moreover, BFOV markedly reduced glycosylated hemoglobin concentration and improved dyslipidemia in STZ-diabetic rats, in a dose-dependent manner (P<0.05, P<0.01), but had no significant effect on non-diabetic rats. CONCLUSION: The organic vanadium complex was found to effectively attenuate diabetic alterations in STZ-diabetic rats.     

运动训练对糖尿病大鼠尾神经传导速度的影响

目的：探讨运动训练对糖尿病大鼠尾神经传导速度（CNCV）的影响。方法：链脲霉素（STZ,55mg/kg）诱导的21只糖尿病大鼠随机平均分配到糖尿病运动8周组（A）、糖尿病运动4周组（B）和糖尿病对照组（C）,实验结束时17只糖尿病大鼠存活,其中A组6只、B组6只和C组5只;12只正常血糖大鼠随机分为正常运动8周组（D,n=6）和正常对照组（E,n=6）。运动组大鼠游泳60min/d,5d/周。实验过程中分别于基线、第4周、第8周时测定大鼠血糖、体重和CNCV。结果：糖尿病大鼠基线时血糖显著高于正常血糖大鼠     

Parameters of antioxidative defense in type 2 diabetic patients with cardiovascular complications

OBJECTIVE. Diabetes‐associated oxidative stress is a consequence of both increased production of free radicals and reduced capacity of antioxidative defense. Prolonged hyperglycemia is the major factor in the pathogenesis of atherosclerosis in diabetes which can lead to cardiovascular complications. The aim of this study was to test the parameters of antioxidative defense in type 2 diabetic patients.

METHODS. A total of 117 type 2 diabetics with and without cardiovascular complications were examined in order to find out the influence of hyperglycemia, type and duration of complications and duration of diabetes on the extent of disorder of antioxidative parameter values: superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), glutathione reductase (GR) and total antioxidant status (TAS).

RESULTS. Compared to healthy control subjects, type 2 diabetic patients with cardiovascular complications (CVC) had significantly lower SOD (P<0.0001), GSH‐Px (P<0.0001), GR ( P = 0.0002) and TAS values (P<0.0001). In type 2 diabetic subjects with CVC, males had significantly lower SOD (778.7±103.2?U/gHb, P<0.01) and GR activities (52.2±8.9?U/L, P<0.001) compared to females (839.3±94.9?U/gHb; 58.5±9.1?U/L). Significant and positive correlation was found between glucose levels and SOD (r = 0.375 for P<0.05) and GSH‐Px (r = 0.384, P<0.05 ) activity in the group of complications‐free diabetics, while significant negative correlation between glucose and GSH‐Px values (r = ?0.382, P<0.05) was found in the group of type 2 diabetics with coronary artery disease (CAD) and hypertension (HTA) and with CAD and acute myocardial infarction (AMI) (r = ?0.860 P<0.05), and highly negative correlation between glucose and SOD levels (r = ?0.590, P<0.05) in the group of diabetic subjects with CAD, AMI and HTA. Likewise, there was highly significant negative correlation of SOD (r = ?0.949, P<0.05) and TAS (r = ?0.393 for P = 0.038) with duration of diabetes in the group of diabetics with CAD and HTA.

CONCLUSION. Our results confirm the hypothesis that there is reduced antioxidative defense in type 2 diabetics with prominent cardiovascular complications, which negatively correlates with glucose concentrations and duration of diabetes and cardiovascular complications.     

Carbohydrate utilization by exercising muscle following pre-exercise glucose ingestion

Summary. The effect on exercising muscle metabolism of prior ingestion of 200 g glucose was examined in six healthy subjects during 40 min leg exercise at 30% of maximal oxygen uptake. Leg glucose uptake during exercise was on average two- to three-fold higher after glucose (E+G) compared to exercise without glucose (E) and could account for 44–48% of the oxidative leg metabolism (control value: 19%, P<0·05-0·01). In contrast to E, which was associated with a significant release of leg lactate, pyruvate and alanine, E+G gave no leg production of lactate or alanine and an uptake of pyruvate. The respiratory exchange ratios (R) were higher during G + E and corresponded to a carbohydrate oxidation of 54–69% as against 46–49% (P0<·05-0·01) during E. Estimated from R-values and leg oxygen and glucose uptakes, carbohydrate oxidation during G<E was almost completely accounted for by blood glucose. During E, on the other hand, carbohydrate oxidation exceeded leg glucose uptake, indicating a small but significant muscle glycogen breakdown (P<0·01). The rate of glycogen utilization during E or G + E was too small to be detected by direct measurements of muscle glycogen content. The results demonstrate that glucose ingestion prior to light exercise is followed by increased uptake and more efficient oxidation of glucose, as well as by insignificant muscle glycogen degradation by exercising muscle. Although the present findings suggest a glycogen-conserving effect of glucose ingestion under these conditions, the main fuel shift is from fat to glucose oxidation.     

Nordkem–An organization to promote the collaboration between clinical laboratories in the Nordic countries

The effects of emeriamine, a new anti-diabetic drug, on exocrine and endocrine pancreatic function in normal and diabetic rats have been studied both in vivo and in vitro. It was found that emeriamine dose-dependently normalized the symptoms of hyperingestion and hyperposia in streptozotocin (STZ)-induced diabetic rats, with fasting glucose levels significantly decreased and insulin levels not changed. In STZ-induced diabetic rats, there was a significant increase in pancreatic lipase and trypsin contents and a sharp decrease in amylase content. These changes in lipase and trypsin, but not in amylase were normalized by administration of emeriamine. In the normal rat, emeriamine had no effect on either serum glucose or insulin levels, but significantly decreased the pancreatic amylase, lipase as well as trypsin contents by 68%, 58% and 51%, respectively. In vitro, emeriamine (10^?8-10^?4 mol l^?1) had no effect on enzyme release from pancreatic acini either under basal or carbachol-stimulated conditions. Emeriamine inhibited glucose-induced insulin release from isolated pancreatic islets. In conclusion, emeriamine has an inhibitory effect on synthesis of pancreatic enzymes and on glucose-stimulated insulin release.     

Experimental diabetes treated with trigonelline: effect on β cell and pancreatic oxidative parameters

Oxidative stress in diabetes coexists with a reduction in the antioxidant status, which can further increase the deleterious effects of free radicals. Trigonelline is the major component of Mirabilis jalapa L., which has been used to treat diabetes in China. The present study was designed to evaluate the beneficial effects of trigonelline against hyperglycemia, hyperlipidemia, β cell damage and antioxidant of pancreas in diabetic rats. Diabetic rats were induced by intraperitoneal injection 35 mg/kg streptozotocin and a high‐carbohydrate/high‐fat diet. Rats were divided into four groups: normal control, diabetic control, trigonelline‐treated diabetic, and glibenclamide‐treated diabetic. After 4‐week treatment, blood glucose, serum insulin, total cholesterol (TC), and triglyceride (TG) levels, insulin content in pancreas, and oxidative stress parameters in pancreatic homogenate were assayed. Pancreas was examined by hematoxylin/eosin staining. Trigonelline significantly decreased blood glucose, TC, and TG levels of diabetic rats. Pancreas‐to‐body weight ratio, insulin level, insulin sensitivity index, insulin content in pancreas, malonaldehyde and nitric oxide contents, and superoxide dismutase, catalase, glutathione and inducible nitric oxide synthase activities were altered in diabetic rats, and were near control levels treated with trigonelline. These findings suggest that trigonelline has beneficial effect for diabetes through decreasing blood glucose and lipid levels, increasing insulin sensitivity index and insulin content, up‐regulating antioxidant enzyme activity and decreasing lipid peroxidation.     

The antilipolytic action of bis(alpha-furancarboxylato)oxovanadium(IV) in adipocytes

BACKGROUND: Previously, bis(alpha-furancarboxylato)oxovanadium(IV)(BFOV) exhibited potent hypoglycemic activity in diabetic animals. We evaluated the effects of BFOV on lipolysis in isolated rat adipocytes and lipid metabolism in fat-fed/streptozotocin (STZ)-induced diabetic rats, an animal model of type 2 diabetes. METHODS: Antilipolytic action of BFOV was investigated by observing free fatty acids (FFA) release in isolated rat adipocytes treated with epinephrine and forskolin. Diabetic rats were induced by high-fat feeding plus STZ injection (25 mg/kg, i.p.). The rats were randomly divided into non-diabetic, diabetic, diabetic-BFOV (0.02, 0.06 and 0.2 mmol/kg) and diabetic-vanadyl sulfate group. All substances were given intragastrically to rats for 4 weeks. The concentrations of blood glucose, serum lipid and leptin, as well as body weight and food intake were determined. RESULTS: FFA release from adipocytes treated with epinephrine was markedly inhibited by BFOV and vanadyl sulfate, with the IC(50) values of 0.30+/-0.20 and 0.46+/-0.26 mmol/l, respectively, but not by insulin. Whereas, the inhibition of vanadyl compounds on FFA release triggered by forskolin in adipocytes were not observed. BFOV dose-dependently reduced serum triglycerides and FFA concentrations when compared with untreated diabetic rats (P<0.05), while it did not influence cholesterol concentrations, similar to vanadyl sulfate. Serum leptin concentration was also decreased both in the BFOV- and vanadyl sulfate-treated diabetic group (P<0.05). Moreover, BFOV markedly reduced blood glucose concentration and food intake (P<0.05), but it did not change the body weight of diabetic rats. CONCLUSION: BFOV has an antilipolytic action in adipocytes mediated by catecholamines. This action was distinct from that of insulin and also not related to inhibiting the activity of adenylate cyclase. In vivo, BFOV could improve dyslipidemia and leptin sensitivity in fat-fed/STZ-diabetic rats.     

Enhancement of glucose toxicity by hyperbaric oxygen exposure in diabetic rats

The side effects of hyperbaric oxygen (HBO) treatment, such as oxidative stress and oxygen toxicity, have long been of interest. However, there are no comprehensive studies evaluating such toxic effects in diabetes mellitus (DM). The purpose of this study was to determine the effects of HBO on glucose homeostasis and histological changes in pancreatic beta-cells of experimentally induced diabetic rats. A total of 24 male Wistar rats were randomly divided into 4 groups: 1) Control group, no diabetic induction without HBO treatment; 2) HBO group, exposed to 100% oxygen at 2.8 ATA (atmosphere absolute) for 2 h once daily, for 7 days; 3) DM group, diabetes induced by streptozotocin (STZ) injection; and 4) DM + HBO group, received both STZ injection and HBO exposure. HBO treatment, with clinically recommended pressures and duration of therapy, was started on day 5 after STZ injection, when the blood glucose levels were significantly increased. After the last HBO treatment, the pancreatic tissues were immunostained to measure the areas of insulin immunoreactive beta-cells in the islets of Langerhans. The blood glucose increased significantly following exposure to HBO, with the highest levels achieved in rats, which had been treated with both HBO and diabetic induction. The area populated with insulin immunoreactive beta-cells decreased significantly following diabetic induction and/or HBO exposure, with the smallest area in DM + HBO group. Thus, HBO exposure enhanced the cytotoxic effect of STZ in the beta-cells of the pancreas. HBO should be cautiously employed in diabetic patients.     

Gosha-jinki-gan (a Herbal Complex) Corrects Abnormal Insulin Signaling

Previous studies have shown that the traditional herbal complexGosha-jinki-gan (GJG) improves diabetic neuropathy and insulinresistance. The present study was undertaken to elucidate themolecular mechanisms related with the long-term effects of GJGadministration on insulin action in vivo and the early stepsof insulin signaling in skeletal muscle in streptozotocin (STZ)diabetes. Rats were randomized into five subgroups: (1) salinetreated control, (2) GJG treated control, (3) 2-unit insulin+ saline treated diabetic, (4) saline + GJG treated diabeticand (5) 2-unit insulin + GJG treated diabetic groups. Afterseven days of treatment, euglycemic clamp experiment at an insulininfusion rate of 6 mU/kg/min was performed in overnight fastedrats. Despite the 2-unit insulin treatment, the metabolic clearancerates of glucose (MCR, ml/kg/min) in diabetic rats were significantlylower compared with the controls (11.4 ± 1.0 vs 44.1± 1.5; P < 0.001), and were significantly improvedby insulin combined with GJG or GJG alone (26 ± 3.2 and24.6 ± 2.2, P < 0.01, respectively). The increasedinsulin receptor (IR)-ß protein content in skeletalmuscle of diabetic rats was not affected by insulin combinedwith GJG administration. However, the decreased insulin receptorsubstrate-1 (IRS-1) protein content was significantly improvedby treatment with GJG. Additionally, the increased tyrosinephosphorylation levels of IR-ß and IRS-1 were significantlyinhibited in insulin combined with GJG treated diabetes. Thepresent results suggest that the improvement of the impairedinsulin sensitivity in STZ-diabetic rats by administration ofGJG may be due, at least in part, to correction in the abnormalearly steps of insulin signaling in skeletal muscle.     

Correction of chronic hyperglycemia with vanadate, but not with phlorizin, normalizes in vivo glycogen repletion and in vitro glycogen synthase activity in diabetic skeletal muscle.

Vanadate has insulin-like activity in vitro and in vivo. To characterize the in vivo mechanism of action of vanadate, we examined meal tolerance, insulin-mediated glucose disposal, in vivo liver and muscle glycogen synthesis, and in vitro glycogen synthase activity in 90% partially pancreatectomized rats. Four groups were studied: group I, sham-operated controls; group II, diabetic rats; group III, diabetic rats treated with vanadate; and group IV, diabetic rats treated with phlorizin. Insulin sensitivity, assessed with the euglycemic hyperinsulinemic clamp technique in awake, unstressed rats, was reduced by approximately 28% in diabetic rats. Both vanadate and phlorizin treatment completely normalized meal tolerance and insulin-mediated glucose disposal. Muscle glycogen synthesis was reduced by approximately 80% in diabetic rats (P less than 0.01) and was completely restored to normal by vanadate, but not by phlorizin treatment. Glycogen synthase activity was reduced in skeletal muscle of diabetic rats (P less than 0.05) compared with controls and was increased to supranormal levels by vanadate treatment (P less than 0.01). Phlorizin therapy did not reverse the defect in muscle glycogen synthase. These results suggest that (a) the defect in muscle glycogen synthesis is the major determinant of insulin resistance in diabetic rats; (b) both vanadate and phlorizin treatment normalize meal tolerance and insulin sensitivity in diabetic rats; (c) vanadate treatment specifically reverses the defect in muscle glycogen synthesis in diabetic rats. This effect cannot be attributed to the correction of hyperglycemia because phlorizin therapy had no direct influence on the glycogenic pathway.     

药物干预对链脲佐菌素诱导的1型糖尿病大鼠心肌病变的影响

目的 探讨1型糖尿病大鼠心肌病理改变及阿司匹林、培哚普利、泼尼松对其心肌病变的影响.方法 30只SD大鼠随机分为糖尿病模型组(n=20)和正常对照组(n=10),糖尿病模型组一次性腹腔注射链脲佐菌素(STZ)60 mg/kg加枸橼酸钠溶液,正常对照组腹腔注射枸橼酸钠溶液.8周后观察2组大鼠的体重和平均血糖浓度.将建模的20只糖尿病大鼠随机分为4组(n=5),第4天起,分别给予生理盐水溶解的阿司匹林、培哚普利、泼尼松灌胃各5只,余5只和正常对照组每日以等体积生理盐水灌胃,共持续8周.8周后取各组大鼠心肌组织,HE染色,光镜和电镜下进行观察和比较.结果 大鼠以STZ注射后3 d血糖浓度≥16.7 mmol/L为造模成功,模型组20只大鼠全部成活,成模后大鼠出现明显多饮、多食、多尿和体重下降,HE染色显示糖尿病大鼠心肌细胞肿胀肥大、变性,核明显增大,心肌纤维断裂、溶解,收缩呈波浪状,排列紊乱,并有炎性细胞的浸润.电镜下可见糖尿病大鼠心肌肌纤维排列不规则,断裂溶解,肌纤维间糖原聚集,线粒体肿胀,线粒体大部分嵴不清晰,细胞间盘增宽.与糖尿病组相比,各药物干预组上述病理改变均有所减轻,而以培哚普利组最为明显.结论 STZ诱导的1型糖尿病大鼠模型制作方法成功率高,血糖值稳定,8周后出现明显的心肌病变,阿司匹林、培哚普利、泼尼松均能使糖尿病大鼠心肌病变有所减轻,以培哚普利最为有效.

Abstract：

Objective To investigate the pathological changes of myocardium in diabetic rats and the effect of aspirin, perindopril, prednisone on the pathological changes of myocardium in type 1 diabetic rats. Methods Thirty SD rats were randomly divided into the following groups: ( 1 ) diabetes mellitus (DM)group ( n = 20): treated with intraperitoneal injection of streptozocin (STZ) 60 mg/kg at one time, diluted in sodium citrate buffer. (2) normal control group (n = 10): intraperitoneal injection of sodium citrate buffer. The blood glucose and the weight were measured regularly for 8 weeks. The 20 diabetic model rats were randomly divided into four groups (n = 5 individually), from the 4th day, the rats were given normal saline dissolved aspirin, perindopril, prednisone gavage respectively, and the normal control group and diabetic group were given an equal volume of saline daily gavage. After 8 weeks, the pathological changes in the cardiac muscle tissue were observed under light microscope and electron microscope. Results Three days after the injection of STZ, the blood glucose in the DM group was higher than 16. 7 mmol/L,20 rats were all modeling successfully. The model rats suffered from polydipsia, polyphagia, polyuria and weight loss significantly. HE staining showed diabetic myocardial cell swell, hypertrophy, degeneration and significant nuclear enlargement; the myocardial fiber fractured,dissolved, contraction wavy and disorganized fibre infiltrated by inflammatory cells. Under electron microscope, diabetic myocardial muscle fibers arranged irregularly, fractured and dissolved; the glycogen between the muscle fiber accumulated, mitochondria swelled, most of the ridges in mitochondria were not clear, cell plate widened. Compared with the diabetic group, the above-mentioned pathological changes reduced in the drug intervention group,and the changes in perindopril group was most significant. Conclusion Injection of STZ 60 mg/kg could successfully induce diabetic in rats and held stable blood glucose level. After 8 weeks, diabetes could cause servere damages in myocardium in the rats, but aspirin, perindopril, prednisone could reduce the cardiomyopathy in diabetic rats,in which perindopril had more positive effect.     

Autonomic neuropathy precedes cardiovascular dysfunction in rats with diabetes

Background Our team previously demonstrated arterial stiffening and cardiac hypertrophy in type 2 diabetic rats at 8 but not 4 weeks after being administered streptozotocin (STZ) and nicotinamide (NA). The present study focused on investigating the effects of type 2 diabetes on cardiac autonomic nerve function in the STZ‐ and NA‐treated animals, using modern spectral estimation technique. Design An autoregressive process was performed to each detrended signal of heart rate and systolic blood pressure measured in the 4‐ and 8‐week STZ‐NA rats with anaesthesia. The power of low‐frequency and high‐frequency oscillations was automatically quantified with each spectral peak by computing the residuals. The closed‐loop baroreflex gain was estimated using the square root of the ratio between heart rate and systolic blood pressure powers in the low‐frequency band. Results Compared with the age‐matched controls, both the 4‐ and 8‐week STZ‐NA diabetic rats had significantly decreased low‐frequency oscillations of heart rate but not systolic blood pressure variability, showing a decline in baroreflex gain (0·451 ± 0·060 and 0·484 ± 0·056 vs. 1·196 ± 0·064 ms mmHg^?1, P < 0·05). On the other hand, the low frequency–high frequency power ratio of the heart period was also diminished in the two diabetic groups, indicating a shift in sympatho‐vagal balance of the heart control (0·472 ± 0·109 and 0·504 ± 0·090 vs. 1·857 ± 0·336, P < 0·05). Conclusions The cardiac autonomic dysfunction in the absence of any significant changes in vascular dynamics, 4 but not 8 weeks after induction of type 2 diabetes, suggests that the diabetic autonomic neuropathy may precede arterial stiffening and cardiac hypertrophy in the STZ‐ and NA‐treated rats.     

Laminin and collagen IV inclusion in immunoisolating microcapsules reduces cytokine‐mediated cell death in human pancreatic islets

Extracellular matrix (ECM) molecules have several functions in pancreatic islets, including provision of mechanical support and prevention of cytotoxicity during inflammation. During islet isolation, ECM connections are damaged, and are not restored after encapsulation and transplantation. Inclusion of specific combinations of collagen type IV and laminins in immunoisolating capsules can enhance survival of pancreatic islets. Here we investigated whether ECM can also enhance survival and lower susceptibility of human islets to cytokine‐mediated cytotoxicity. To this end, human islets were encapsulated in alginate with collagen IV and either RGD, LRE or PDSGR, i.e. laminin sequences. Islets in capsules without ECM served as control. The encapsulated islets were exposed to IL‐1β, IFN‐γ and TNF‐α for 24 and 72 h. All combinations of ECM improved the islet cell survival, and reduced necrosis and apoptosis after cytokine exposure (P < 0.01). Collagen IV‐RGD and collagen IV‐LRE reduced danger‐associated molecular patterns (DAMPs) release from islets (P < 0.05). Moreover, collagen IV‐RGD and collagen IV‐PDSGR, but not collagen IV‐LRE, reduced NO release from encapsulated human islets (P < 0.05). This reduction correlated with a higher oxygen consumption rate (OCR) of islets in capsules containing collagen IV‐RGD and collagen IV‐PDSGR. Islets in capsules with collagen IV‐LRE showed more dysfunction, and OCR was not different from islets in control capsules without ECM. Our study demonstrates that incorporation of specific ECM molecules such as collagen type IV with the laminin sequences RGD and PDSGR in immunoisolated islets can protect against cytokine toxicity.     

大鼠糖尿病性阴茎勃起功能障碍模型的建立

目的探讨链霉佐菌素（STZ）腹腔注射法建立糖尿病（DM）阴茎勃起功能障碍（ED）动物模型的可行性，以便找到一种发病机制与临床接近的疾病模型。方法模型组雄性大鼠，腹腔注射STZ；正常对照组大鼠，腹腔注射枸椽酸钠液。4d后，快速法测定血糖；10周后，分别测定2组大鼠阴茎海绵体内压（ICP）。结果动物模型血糖浓度：实验组（335．8±62．8）mg／dl显著高于对照组（99．4±24．4）mg／dl（p〈0．01）。DM大鼠基础ICP和刺激勃起神经ICP均明显低于正常大鼠（p〈0．01）。结论腹腔注射STZ诱导糖尿病大鼠出现典型的糖尿病临床症状，血糖明显增高，ICP下降，勃起功能明显受损。     

Combined vitamins (C and E) and insulin improve oxidative stress and pancreatic and hepatic injury in alloxan diabetic rats

The aim of the present study is to determine if a combination of vitamins (C and E) has any advantage over insulin therapy on lipid peroxidation, antioxidant activity, liver dysfunction parameters, and histological changes in the alloxan-induced diabetic rats. The enzymatic activities of glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) and the lipid peroxidation product, thiobarbituric acid-reacting substances (TBARS) were measured in liver and pancreas as indicators of antioxidation in these tissues. The liver dysfunction parameters: the activity of lactate dehydrogenase (LDH), gamma glutamyl transferase (GGT), phosphatase alkalines (PAL), aspartate and lactate transaminase (AST and ALT) were measured in serum. In diabetic rats, the TBARS contents of the liver and pancreatic tissues were found to have significantly increased as compared to non-diabetic rats (P < 0.001). The SOD, CAT, and GPX activities in the liver and pancreas in diabetic rats significantly decreased as compared to normal rats (P < 0.001). AST, ALT, LDH, GGT, and PAL activities increased in the diabetic rats (p > 0.05). In diabetic rats treated with insulin or with combined vitamins (C and E), an ameliorative effect was observed. This amelioration was more pronounced in the group of rats treated with combined vitamins (C and E).     

Muscle glycogen concentration during recovery after prolonged severe exercise in fasting subjects

The influence of 12 h of fasting after prolonged severe exercise on the muscle glycogen concentration was studied in 5 normal subjects. The subjects exercised in the post absorptive state at 70% of max. V_o2 till exhaustion, then rested for 12 h. No food was allowed during recovery. Blood samples and muscle biopsies were obtained before exercise, immediately after the cessation of exercise, and after 2, 4, 6, 9 and 12 h of recovery. Muscle glycogen content decreased from 70.4 ± 3.0 to 21.6 ±3.9 mmol glucosyl units/kg w.w. in response to exercise. After 4 h of recovery muscle glycogen had increased to 28.8 + 3.6 mmol glucosyl units/kg (P<0.025). During the next 8 h of recovery no further increase in glycogen concentration was observed. Mean plasma glucose concentration decreased from 5.25±0.16 to 4.37±0.18 mmol/1 during exercise (P<0.001). No change in the plasma glucose level was observed during recovery. Immunoreactive insulin (IRI) concentration decreased from 15.9±1.0 to 10.2±0.5 μU/ml (P<0.001) during exercise, and remained at this level during recovery. It is concluded that some muscle glycogen repletion may occur after prolonged, severe exercise even under fasting conditions. It is suggested that this may proceed through an increased hepatic gluconeogenesis.     

Ferulic acid improves glucose homeostasis by modulation of key diabetogenic activities and restoration of pancreatic architecture in diabetic rats

There are increasing concerns on the rising cases of diabetes mellitus with type 2 diabetes (T2D) being of major interest as well as the cost of its treatment. Plant phenolic compounds are natural and potent antioxidants that have been widely reported for their antidiabetic activities properties, one of which is ferulic acid. The effect of ferulic acid (FA) on major diabetogenic activities and pancreatic architecture linked to T2D was investigated in T2D rats. T2D was induced in male Sprague–Dawley rats using the fructose-streptozotocin model. Diabetic rats were treated with FA at 150 or 300 mg/kg bodyweight (bw). Normal control consisted of rats administered with food and water, while diabetic control consisted of untreated diabetic rats. Metformin was used as the standard drug. The rats were humanely sacrificed after 5 weeks of treatment. Their blood, liver, and pancreas were collected for analysis. Total glycogen content and carbohydrate metabolic enzymes activities were analyzed in the liver, while the pancreas and serum from blood were analyzed for oxidative stress biomarkers, purinergic and cholinergic enzyme activities, and amylase and lipase activities. The pancreatic tissue was further subjected to microscopic and histological examinations. FA caused a significant (p < 0.05) decrease in blood glucose level, with concomitant increase in serum insulin level. Treatment with FA also led to elevated levels of GSH, HDL-c, SOD, and catalase activities, while concomitantly suppressing malondialdehyde, cholesterol, triglyceride, LDL-c, NO, ALT, AST, creatinine, urea, and uric acid levels, acetylcholinesterase, ATPase, ENTPDase, 5′-nucleotidase, lipase, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-biphosphatase activities. Histology analysis revealed an intact pancreatic morphology in FA-treated diabetic rats. While transmission electron microscopy (TEM) analysis revealed an intact pancreatic ultrastructure and increased number of insulin granules in β-cells. Taken together, these results portray that the antidiabetic potentials of ferulic acid involves modulation of major diabetogenic activities and maintenance of the pancreatic ultrastructure architecture.     

仙灵脾改善2型糖尿病大鼠胰岛素抵抗机制的初步探讨

目的探讨仙灵脾改善2型糖尿病(T2DM)大鼠胰岛素抵抗的机制。方法 70只Wistar大鼠,随机选取10只作为正常对照组,予普通饲料喂养;60只为造模组,采用高脂、高糖饲料加小剂量链脲佐菌素建立T2DM大鼠模型,其中成模的44只大鼠随机分为T2DM模型组16只、仙灵脾组16只、二甲双胍组12只。仙灵脾组灌服中药仙灵脾3.0g·kg-1·d-1;模型组和正常对照组予等量生理盐水;二甲双胍组予二甲双胍混悬液10mg·kg-1·d-1灌胃给药。用药8周末,取血检测空腹血糖(FBG)、空腹胰岛素(FINS)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、单核细胞趋化蛋白-1(MCP-1),计算胰岛素敏感指数(ISI)。结果与T2DM模型组相比,仙灵脾组、二甲双胍组FBG、FINS、TNF-α、IL-6及MCP-1水平明显降低(P均<0.05),ISI水平明显升高(P均<0.05);与二甲双胍组比较,仙灵脾组FBG较高,ISI较低(P均<0.05)。结论仙灵脾可以通过改善炎症反应来改善T2DM大鼠的胰岛素抵抗。