Oral administration of levan polysaccharide reduces the alloxan-induced oxidative stress in rats

This study aimed to evaluate the effect of a polysaccharide named levan, which was produced by new isolated bacteria, on oxidative stress and hyperglycemia in alloxan-induced diabetic rats. Levan polysaccharide was given in drinking water for 60 days at a daily dose equivalent to 2%. The oral administration of levan in diabetic rats caused a decrease in glucose level in plasma and an increase of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities in both pancreas and liver. Furthermore, a protective action against hepatic and pancreatic toxicity in diabetic rats was clearly observed. Furthermore, a significant decrease in hepatic and pancreatic indices toxicity was observed, i.e., alkalines phosphatases (ALP), aspartate and lactate transaminases (AST and ALT), lactate deshydrogenases (LDH) activities and the thiobarbituric acid-reactive substances (TBARs). These beneficial effects of levan were confirmed by histological findings in hepatic and pancreatic tissues of diabetic rats. This study demonstrates for the first time that levan is efficient in inhibiting hyperglycemia and oxidative stress induced by diabetes and suggests that administration of levan may be helpful in the prevention of diabetic complications associated with oxidative stress.     

Hypolipidemic effect of diet supplementation with bacterial levan in cholesterol-fed rats

Levan polysaccharide, a type of fructan, has been shown to have industrial applications as a new industrial gum in the fields of cosmetics, foods like dietary fiber and pharmaceutical goods. The objective of this current study was to investigate the possible hypolipidemic and antioxidative effects of levan in rats fed with a high-cholesterol diet. Animals were allocated into four groups of six rats each: a normal diet group (Control), normal rats received levan (L), a high-cholesterol diet group (Chol) and a high-cholesterol diet with a daily dose of levan equivalent to 5%. Treated hypercholesterolemic rats were administrated with levan in drinking water through oral gavage for 60 days. After the treatment period, the plasma antioxidant enzymes and lipid profiles were determined. Our results show that treatment with levan polysaccharide positively changed plasma antioxidant enzyme activities and lipid profiles (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides) in cholesterol-rats, and thus may have potential hypolipidemic and antioxidant effects. Levan could protect against oxidative stress linked atherosclerosis and decrease the atherogenic index.     

Curcuminoids modulates oxidative damage and mitochondrial dysfunction in diabetic rat brain

Diabetes exacerbates neuronal injury induced by hyperglycemia mediated oxidative damage and mitochondrial dysfunction. The aim of the present study is to investigate the effects of curcuminoids, polyphenols of Curcuma longa (L.) on oxidative stress and mitochondrial impairment in the brain of streptozotocin (STZ)-induced diabetic rats. A marked increase in lipid peroxidation and nitrite levels with simultaneous decrease in endogenous antioxidant marker enzymes was observed in the diabetic rat brain, which was restored to normal levels on curcuminoids treatment. Down-regulation of mitochondrial complex I and IV activity caused by STZ induction was also up-regulated on oral administration of curcuminoids. Moreover, curcuminoids administration profoundly elevated the ATP level, which was earlier reduced in the diabetic brain. These results suggest that curcuminoids exhibit a protective effect by accelerating antioxidant defense mechanisms and attenuating mitochondrial dysfunction in the brain of diabetic rats. Curcuminoids thus may be used as a promising therapeutic agent in preventing and/or delaying the progression of diabetic complications in the brain.     

Hypoglycemic and antioxidant effects of phenolic extracts and purified hydroxytyrosol from olive mill waste in vitro and in rats

This study aimed to evaluate the effect of phenolic extract and purified hydroxytyrosol (HT) from olive mill waste (OMW) on oxidative stress and hyperglycemia in alloxan-induced diabetic rats. The OMW biophenols were extracted using ethyl acetate. The obtained extract was fractionated by solid phase extraction (SPE) experimentation to generate two fractions: (F1) and (F2). HPLC-UV and HPLC-MS analysis showed that (F1) was made of known OMW monomeric phenolics mainly hydroxytyrosol (HT) while (F2) contained oligomeric and polymeric phenols such as verbascosid and ligstrosid. (HT) was purified from (F1) using silica gel-column chromatography and silica gel-TLC techniques. In incubated pancreas, supplementation of OMW fractions enhanced insulin secretion. The administration of OMW extract fractions (F1) and (F2) as well as purified (HT) in diabetic rats caused a decrease in glucose level in plasma and an increase in renal superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities in liver and kidney. Furthermore, a protective action against hepatic and renal toxicity in diabetic rats was clearly observed. Furthermore, a significant decrease in hepatic and renal indices toxicity was observed, i.e. alkalines phosphatases (ALP), aspartate and lactate transaminases (AST and ALT) activities and the thiobarbituric acid-reactive substances (TBARs), total and direct bilirubin, creatinine and urea levels. In addition, (F1), (F2) and especially (HT) decreased triglycerides (TG), total-cholesterol (T-Ch) and higher HDL-cholesterol (HDL-Ch) in serum. These beneficial effects of OMW biophenols were confirmed by histological findings in hepatic, renal and pancreatic tissues of diabetic rats. This study demonstrates for the first time that OMW polyphenols and especially (HT) are efficient in inhibiting hyperglycemia and oxidative stress induced by diabetes and suggests that administration of HT may be helpful in the prevention of diabetic complications associated with oxidative stress.     

Atorvastatin reduces the plasma lipids and oxidative stress but did not reverse the inhibition of prostacyclin generation by aortas in streptozotocin diabetic rats

The effect of atorvastatin (Lipitor) on diabetes-induced changes in plasma lipids, oxidative stress and the ability of aortic tissues to generate prostacyclin was studied in streptozotocin diabetic rats. In diabetic rats, plasma total cholesterol, triglycerides and serum glucose significantly increased compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not affect hyperglycemia but significantly reduced plasma total cholesterol and triglycerides compared to diabetic rats. The oxidative stress markers urinary isoprostane, liver thiobarbituric acid reactive substances (TBARS) and plasma protein carbonyl content significantly increased in diabetic rats compared to nondiabetic rats. Atorvastatin admnistration to diabetic rats significantly reduced oxidative stress levels compared to diabetic rats, but urinary isoprostane and liver TBARS remained significantly higher than nondiabetic rats. Prostacyclin (PGI(2)) generation by aortic tissues significantly decreased in diabetic rats compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not reverse that inhibition. These results were discussed in the light of the possible effects of hyperglycemia and statins on NAD(P)H-oxidase and cyclooxygenase-2 activities and the genetic difference between rats and other mammals regarding the level of vascular superoxide dismutase (SOD) activity.     

Therapeutic effects of stem cell on hyperglycemia,hyperlipidemia, and oxidative stress in alloxan-treated rats

Diabetes mellitus is the most common endocrine disorder that affects more than 285 million people worldwide. The purpose of this study was to investigate the effect of mesenchymal stem cells (MSCs) from the bone marrow of albino rats, on hyperglycemia, hyperlipidemia, and oxidative stress induced by intraperitoneal injection (i.p.) of alloxan at a dose of 150 mg/kg in rats. Injection of alloxan into rats resulted in a significant increase in serum glucose, total cholesterol, triglyceride, low density lipoprotein cholesterol, and sialic acid level and a significant decrease in serum insulin, high density lipoprotein-cholesterol, vitamin E, and liver glycogen as compared to their corresponding controls. Also, oxidative stress was noticed in pancreatic tissue as evidenced by a significant decrease in glutathione level, superoxide dismutase, glutathione-S-transferase activities, also a significant increase in malondialdehyde and nitric oxide levels when compared to control group. Treatment of diabetic rats with MSCs stem cells significantly prevented these alterations and attenuated alloxan-induced oxidative stress. In conclusion, rat bone marrow harbors cells that have the capacity to differentiate into functional insulin-producing cells capable of controlling hyperglycemia, hyperlipidemia, and oxidative stress in diabetic rats. This may be helpful in the prevention of diabetic complications associated with oxidative stress.     

Low-carbohydrate diet and oxidative stress in diabetic and nondiabetic rats

Hyperglycemia of diabetes has been implicated in increased tissue oxidative stress, with consequent development of secondary complications. Thus, stabilizing glucose levels near normal levels is of utmost importance. Because diet influences glycemic control, this study investigated whether a low-carbohydrate (5.5%) diet confers beneficial effects on the oxidative status of the heart, kidney, and liver in diabetes. Male and female normal and diabetic rats were fed standard chow (63% carbohydrates) or low-carbohydrate diet for 30 days. Elevated glucose, HbA(1c), and alanine and aspartate aminotransferases in diabetic animals were reduced or normalized by the low-carbohydrate diet. While diabetes increased cardiac activities of glutathione peroxidase and catalase, low-carbohydrate diet normalized cardiac glutathione peroxidase activity in diabetic animals, and reduced catalase activity in females. Diabetic rats fed low-carbohydrate diet had altered activities of renal glutathione reductase and superoxide dismutase, but increased renal glutathione peroxidase activity in diabetic animals was not corrected by the test diet. In the liver, diabetes was associated with a decrease in catalase activity and glutathione levels and an increase in glutathione peroxidase and gamma-glutamyltranspeptidase activities. Decreased hepatic glutathione peroxidase activity and lipid peroxidation were noted in diet-treated diabetic rats. Overall, the low-carbohydrate diet helped stabilize hyperglycemia and did not produce overtly negative effects in tissues of normal or diabetic rats.     

Sodium Tungstate Attenuate Oxidative Stress in Brain Tissue of Streptozotocin-Induced Diabetic Rats

High blood glucose concentration in diabetes induces free radical production and, thus, causes oxidative stress. Damage of cellular structures by free radicals play an important role in development of diabetic complications. In this study, we evaluated effects of sodium tungstate on enzymatic and nonenzymatic markers of oxidative stress in brain of streptozotocin (STZ)-induced diabetic rats. Rats were divided into four groups (ten rats in each group): untreated control, sodium tungstate-treated control, untreated diabetic, and sodium tungstate-treated diabetic. Diabetes was induced with an intraperitoneal STZ injection (65 mg/kg body weight), and sodium tungstate with concentration of 2 g/L was added to drinking water of treated animals for 4 weeks. Diabetes caused a significant increase in the brain thiobarbituric acid reactive substances (P < 0.01) and protein carbonyl levels (P < 0.01) and a decrease in ferric reducing antioxidant power (P < 0.01). Moreover, diabetic rats presented a reduction in brain glucose-6-phosphate dehydrogenase (21%), superoxide dismutase (41%), glutathione peroxidase (19%), and glutathione reductase (36%) activities. Sodium tungstate reduced the hyperglycemia and restored the diabetes-induced changes in all mentioned markers of oxidative stress. However, catalase activity was not significantly affected by diabetes (P = 0.4), while sodium tungstate caused a significant increase in enzyme activity of treated animals (P < 0.05). Data of present study indicated that sodium tungstate can ameliorate brain oxidative stress in STZ-induced diabetic rats, probably by reducing of the high glucose-induced oxidative stress and/or increasing of the antioxidant defense mechanisms.     

Augmentation of hepatic and renal oxidative stress and disrupted glucose homeostasis by monocrotophos in streptozotocin-induced diabetic rats

Several recent studies have demonstrated that organophosphorus insecticides (OPI) possess the potential to disrupt glucose homeostasis leading to hyperglycemia in experimental animals. The propensity of OPI to induce hyperglycemia along with oxidative stress may have far-reaching consequences on diabetic outcomes and associated complications. The primary objective of this study was to assess the potential of monocrotophos (MCP), an extensively used OPI, on hepatic and renal oxidative stress markers and dysregulation of hepatic glucose homeostasis in experimentally induced diabetic rats. Rats rendered diabetic by a single dose of streptozotocin (60 mg/kg b.w) were orally administered MCP (0.9 mg/kg b.w/d for 5 d). Monocrotophos per se caused only a marginal increase in blood glucose levels but significantly elevated the blood glucose levels and also disrupted glucose homeostasis by depleting liver glycogen content and increasing the gluconeogenetic enzyme activities in diabetic rats. Experimentally induced diabetes was also associated with alterations in antioxidant enzymes in liver and kidney. MCP markedly enhanced lipid peroxidation in kidney and altered the enzymatic antioxidant defense mechanisms in both liver and kidney of diabetic rats. Collectively our data provides evidence that MCP has the propensity to augment the oxidative stress and further disrupt glucose homeostasis in diabetic rats.     

Comparative and combined effect of chlorogenic acid and tetrahydrocurcumin on antioxidant disparities in chemical induced experimental diabetes

The present study evaluates the combined effect of tetrahydrocurcumin and chlorogenic acid on oxidative stress in streptozotocin–nicotinamide-induced diabetic rats. Rats were rendered diabetic by a single intraperitoneal injection (i.p) of streptozotocin (45 mg/kg BW), 15 min after an i.p injection of nicotinamide (110 mg/kg BW). The levels of fasting plasma glucose and insulin were estimated. As an index of oxidative stress, the levels of enzymic antioxidants and lipid peroxidation products were analyzed in liver and kidney. Diabetic rats showed an increase in the levels of fasting plasma glucose, lipid peroxidative products such as thiobarbituric acid reactive substances and lipid hydroperoxides and a decrease in plasma insulin, and enzymic antioxidants viz., superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase. Combined administration of tetrahydrocurcumin (80 mg/kg BW) and chlorogenic acid (5 mg/kg BW) to diabetic rats for 45 days, reversed the biochemical changes to near normal. The above findings were supported by histological observations of the liver and kidney. Together the present study clearly reflects that combined dosage of tetrahydrocurcumin and chlorogenic acid augments enzymic antioxidants with a concomitant decrease in lipid peroxidation and protects against streptozotocin–nicotinamide-induced type 2 diabetes in experimental rats.     

Protective effects of vitamins (C and E) and melatonin co-administration on hematological and hepatic functions and oxidative stress in alloxan-induced diabetic rats

The present study aimed to investigate the potential effects of vitamins (C and E)/melatonin co-administration on the hematologic and hepatic functions and oxidative stress in alloxan-induced diabetic rats. The intraperitoneal injection of alloxan (120 mg/kg b.w. for 2 days) induced a significant increase of blood glucose levels (hyperglycemia) associated with serious hematologic disorders (P?<?0.01) evidenced by the decrease in the levels of red blood cell count (RBC) (?18 %), hematocrit (Ht) (?18 %), hemoglobin content (Hb) (?36 %), mean corpuscular hemoglobin (MCH) (?17 %), and mean corpuscular hemoglobin concentration (MCHC) (?16 %). The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and the plasmatic levels of total cholesterol and triglyceride contents of diabetic rats were, however, noted to undergo significant increases by 42 % (P?<?0.01), 134 % (P?<?0.001), 27.5 % (P?<?0.01), 147 % (P?<?0.001), and 67 % (P?<?0.01), respectively, as compared to the control animals. Furthermore, a significant increase in malondialdehyde (MDA) content and a significant decrease in superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were observed in the plasma and hepatic tissues of diabetic rats when compared to the controls. Interestingly, the treatment with vitamins (C, E) in combination with melatonin was noted to reduce the plasma levels of glucose, lower the MDA levels, and restore the hematologic parameters and biochemical and antioxidant levels of diabetic rats back to normal values, alleviating diabetes metabolic disorders in rats.     

Antihyperglycemic, hypolipidemic and antioxidant activities of ethanolic extract of Commiphora mukul gum resin in fructose-fed male Wistar rats

High fructose feeding (66?% of fructose) induces type-2 diabetes in rats, which is associated with the insulin resistance, hyperinsulinemia, hypertriglyceridemia and oxidative stress. The present study was undertaken to evaluate the effect of ethanol extract of Commiphora mukul gum resin (CMEE) on blood glucose, plasma insulin, lipid profiles, reduced glutathione, lipid peroxidation, protein oxidation and enzymatic antioxidants like superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, glutathione-S-transferase in fructose-induced type-2 diabetic rats. A significant gain in body weight, hyperglycemia, hyperinsulinemia, increased lipid profiles, lipid peroxidation, protein oxidation and decreased reduced glutathione, activities of enzymatic antioxidants and insulin sensitivity (increased homeostasis assessment assay) were observed in high-fructose-induced diabetic rats. The administration of CMEE (200?mg/kg/day) daily for 60?days in high-fructose-induced diabetic rats reversed the above parameters significantly. CMEE has the ability to improve insulin sensitivity and delay the development of insulin resistance, aggravate antioxidant status in diabetic rats and may be used as an adjuvant therapy for patients with insulin resistance.     

Hypoglycemic activity of a polyphenolic oligomer-rich extract of Cinnamomum parthenoxylon bark in normal and streptozotocin-induced diabetic rats

Cinnamon bark has been reported to be effective in the alleviation of diabetes through its antioxidant and insulin-potentiating activities. The water-soluble polyphenolic oligomers found in cinnamon are thought to be responsible for this biological activity. In this study, the hypoglycemic activity of a polyphenolic oligomer-rich extract from the barks of Cinnamomum parthenoxylon (Jack) Nees was studied in normal, transiently hyperglycemic, and streptozotocin (STZ)-induced diabetic rats. Oral administration of the extract at doses of 100, 200, and 300 mg/kg body wt. caused significant changes in body weight loss and fasting blood glucose levels of normal rats. In STZ-induced diabetic rats, after administration of the extract at doses of 100, 200, and 300 mg/kg body wt. over 14 days, the blood glucose levels were decreased by 11.1%, 22.5%, and 38.7%, respectively, and the plasma insulin levels were significantly increased over pre-treatment levels. In an oral glucose tolerance test, the extract produced a significant decrease in glycemia 90 min after the glucose pulse. These results suggest that Cinnamomum parthenoxylon polyphenolic oligomer-rich extract could be potentially useful for post-prandial hyperglycemia treatment.     

Hypoglycemic and antioxidant effect of oleuropein in alloxan-diabetic rabbits

Patients with diabetes mellitus are likely to develop certain complication such as retinopathy, nephropathy and neuropathy as a result of oxidative stress and overwhelming free radicals. Treatment of diabetic patients with antioxidant may be of advantage in attenuating these complications. Oleuropein, the active constituent of olive leaf (Olea europaea), has been endowed with many beneficial and health promoting properties mostly linked to its antioxidant activity. This study aimed to evaluate the significance of supplementation of oleuropein in reducing oxidative stress and hyperglycemia in alloxan-induced diabetic rabbits. After induction of diabetes, a significant rise in plasma and erythrocyte malondialdehyde (MDA) and blood glucose as well as alteration in enzymatic and non-enzymatic antioxidants was observed in all diabetic animals. During 16 weeks of treatment of diabetic rabbits with 20 mg/kg body weight of oleuropein the levels of MDA along with blood glucose and most of the enzymatic and non-enzymatic antioxidants were significantly restored to establish values that were not different from normal control rabbits. Untreated diabetic rabbits on the other hand demonstrated persistent alterations in the oxidative stress marker MDA, blood glucose and the antioxidant parameters. These results demonstrate that oleuropein may be of advantage in inhibiting hyperglycemia and oxidative stress induced by diabetes and suggest that administration of oleuropein may be helpful in the prevention of diabetic complications associated with oxidative stress.     

Tissue specific expression and immunohistochemical localization of glutathione S-transferase in streptozotocin induced diabetic rats: modulation by Momordica charantia (karela) extract

In streptozotocin (STZ)-induced diabetes, destruction of pancreatic beta-cell causes an acute shortage of insulin. Increased oxidative stress is believed to be one of the main factors in the etiology and complications of diabetes. In this study we have reported hyperglycemia and glutathione-associated oxidative stress in rats one week after treatment with STZ. In our previous studies, we have reported oxidative stress-related changes in xenobiotic metabolism in tissues from STZ-induced chronic diabetic rats. Here, we demonstrate by immunohistochemistry, that glutathione S-transferase (GST) isoenzymes are differentially expressed in the liver, kidney and testis of diabetic rats. The distribution of GST isoenzymes was found to be tissue- and regio-specific. In addition, we have also shown that treatment with an extract of Momordica charantia (karela), an antidiabetic herb, modulates GST expression in diabetic rats and reverts them to the normal distribution as seen in the tissues of control rats. These results suggest that glutathione metabolism and GST distribution in the tissues of diabetic rats may play an important role in the etiology, pathology and prevention of diabetes.     

Therapeutic effect of green tea extract on oxidative stress in aorta and heart of streptozotocin diabetic rats

Hyperglycemia induced oxidative stress has been proposed as a cause of many complications of diabetes including cardiac dysfunction. The present study depicts the therapeutic effect of green tea extract on oxidative stress in aorta as well as heart of streptozotocin diabetic rats. Six weeks after diabetes induction, green tea was administered orally for 4 weeks [300 mg (kg body weight)(-1) day (-1)]. In aorta and heart of diabetic rats there was a significant increase in the activity of superoxide dismutase, catalase and glutathione peroxidase with an increase in lipid peroxides. Diabetic rats showed a significant decrease in the levels of serum and cardiac glutathione. Green tea administration to diabetic rats reduced lipid peroxides and activity of antioxidant enzymes whereas increased glutathione content. The results demonstrate that the induction of antioxidant enzymes in diabetic rats is not efficient and sufficient to reduce the oxidative stress. But green tea by providing a competent antioxidative mechanism ameliorates the oxidative stress in the aorta and heart of diabetic rats. The study suggests that green tea may provide a useful therapeutic option in the reversal of oxidative stress induced cardiac dysfunction in diabetes mellitus.     

Resveratrol Attenuates Copper and Zinc Homeostasis and Ameliorates Oxidative Stress in Type 2 Diabetic Rats

Diabetes is a common metabolic disorder characterized by elevated blood glucose level. Trace element homeostasis causes disturbances in diabetes due to hyperglycemia. Superoxide dismutase (SOD), an antioxidant enzyme, contains zinc and copper ions as its cofactors. Defects in SOD level and activity have been observed in diabetes. Resveratrol (RSV) has displayed hypoglycemic effects and is proven to improve oxidative stress. The aim of the present study was to examine the possible effects of RSV on blood glucose level, serum copper and zinc levels, SOD, and a number of other oxidative markers in type 2 diabetic rats. Diabetes was induced in male Wistar rats with administration of streptozotocin and nicotine amide. The studied groups containing six animals per group were as follows: group 1 normal control group; group 2 diabetic control group; groups 3, 4, and 5 diabetic rats that received 1, 5, and 10 mg/kg body weight of RSV, respectively for 30 days. Serum glucose, copper, zinc, SOD activity, total oxidant status (TOS) as well as thiol groups were all measured. Blood glucose in RSV treated groups significantly decreased. Similarly, copper significantly decreased in diabetic groups treated with RSV. Treatment with 10 mg/kg RSV resulted in significantly increased serum zinc. Furthermore, Cu/Zn ratio was observed to decrease in treated groups compared with untreated diabetic control group. RSV treated groups revealed an increased level of SOD activity as well as improved oxidative status. In summary, the results showed that RSV has potential hypoglycemic effect, attenuates trace element homeostasis, and consequently increases SOD activity level.     

Protective effects of either C-peptide or l-arginine on pancreatic β-cell function,proliferation, and oxidative stress in streptozotocin-induced diabetic rats

Diabetes and cardiometabolic risk factors including hypertension and dyslipidemia are the major threats to human health in the 21st century. Apoptosis in pancreatic tissue is one of the major causes of diabetes type 1 progression. The aim of this study was to investigate the effects of C-peptide or l -arginine on some cardiometabolic risk factors, pancreatic morphology, function and apoptosis, and the mechanisms of their actions. Forty adult male albino rats were divided into four equal groups: 1—control nondiabetic, 2—diabetic (no treatment), 3—diabetic + C-peptide, and 4—diabetic + l -arginine. Diabetes was induced by a single intraperitoneal injection of high dose streptozotocin. At the end of the experiment, sera glucose, insulin levels, total antioxidant capacity (TAC), malondialdehyde (MDA), nitric oxide (NO), and pancreatic MDA, TAC, and B-cell lymphoma 2 were measured. The morphology and proliferating activity of the pancreas were examined by hematoxylin and eosin histological stain, proliferative cell nuclear antigen (PCNA), and insulin antibodies. Our results showed that induction of diabetes caused hyperglycemia, dyslipidemia, and oxidative stress. However, administration of C-peptide or l -arginine significantly improved the pancreatic histopathology with a significant increase in the area % of insulin immunoreactivity, the number of PCNA immunopositive cells, the number of islets, and the diameter of islets compared with the diabetic group. C-peptide treatment of the diabetic rats completely corrected these errors, while l -arginine partially antagonized the above diabetic complications. So the administration of C-peptide as an adjuvant therapy in type 1 diabetes can significantly decrease apoptosis of pancreas and subsequent progression of diabetes complication.