Antihyperglycemic effect of extra virgin sacha inchi oil in type 2 diabetic rats: Mechanisms involved in pancreatic ß-cell function and apoptosis.

Background and aim: The purpose of the study was to investigate the anti-hyperglycemic effect of extra virgin sacha inchi oil (EVSIO) and its possible mechanisms and actions against pancreatic ß-cell death and dysfunction in type 2 diabetic (T2D) rats. Experimental procedure: T2D rats were induced with a high-fat diet and low-dose of streptozotocin. The rats were then treated for 5 weeks with EVSIO (0.5, 1, and 2 ml/kg), or pioglitazone. Biochemical and histopathological studies, oxidative and inflammatory markers, and expression of apoptotic-related proteins were then evaluated. Results: EVSIO treatment exhibited a dose-dependent reduction of fasting blood glucose, area under the curve of glucose, total cholesterol, and triglyceride levels in the diabetic rats, while improved pancreatic ß-function was demonstrated by increasing pancreatic and serum insulin levels. EVSIO treatment effectively lowered atrophic pancreatic islets and reduced the level of serum and pancreatic MDA in the diabetic rats. In addition to serum and pancreatic GPx activities in the diabetic rats, EVSIO also augmented serum SOD. Increased levels of NF-κB, TNF-α and IL-6 present in the diabetic rats were greatly reduced by EVSIO treatment. Furthermore, EVSIO revealed an anti-apoptotic effect on the diabetic rat pancreas by upregulating Bcl-2, and downregulating Bax and cleaved caspase-3 protein expression. Conclusion: The overall study results demonstrated the potential anti-hyperglycemic effect of EVSIO in the diabetic rats. The beneficial effects of EVSIO may be attributed to its ability to improve pancreatic ß-cell function and ameliorate ß-cell apoptosis by inhibiting oxidative stress and inflammatory cytokines.

Mango (Mangifera indica L.) seed kernel extract suppresses hyperglycemia by modulating pancreatic ß cell apoptosis and dysfunction and hepatic glucose metabolism in diabetic rats.

This study investigated the anti-hyperglycemic action of mango seed kernel extract (MKE) and various mechanisms involved in its actions to improve pancreatic ß cells and hepatic carbohydrate metabolism in diabetic rats. An intraperitoneal injection of 60 mg/kg of streptozotocin (STZ) followed by 30 consecutive days of treatment with MKE (250, 500, and 1000 mg/kg body weight) was used to establish a study group of diabetic rats. Using liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS) for identification, 26 chemical compounds were found in MKE and the high-performance liquid chromatography (HPLC) analysis of the MKE also revealed the existence of mangiferin, gallic acid, and quercetin. The results confirmed that in each diabetes-affected rat, MKE mitigated the heightened levels of fasting blood glucose, diabetic symptoms, glucose intolerance, total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C). As demonstrated by a remarkable increment in serum and pancreatic insulin, the diabetic pancreatic ß cell function was potentiated by treating with MKE. The effect of MKE on diabetic pancreatic apoptosis clearly reduced the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells, which was related to diminished levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and Bax and an increase in Bcl-xL protein expression. Furthermore, diabetes-induced liver damage was clearly ameliorated along with a notable reduction in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and abnormal liver histology. By enhancing anti-oxidant superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, MKE alleviated diabetes-induced pancreatic and liver oxidative damage, as demonstrated by diminished levels of malondialdehyde. In minimizing the expression levels of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase-1 proteins in the diabetic liver, MKE also enhanced glycogen content and hexokinase activity. Collectively, these findings indicate that by suppressing oxidative and inflammatory processes, MKE exerts a potent anti-hyperglycemic activity in diabetic rats which serve to protect pancreatic ß cell apoptosis, enhance their function, and improve hepatic glucose metabolism.

Effects of Cultured Cordycep militaris on Sexual Performance and Erectile Function in Streptozotocin-Induced Diabetic Male Rats.

Cordyceps militaris (CM), a valuable edible and medicinal fungus, has been used as traditional medicine to treat health conditions, as well as hyposexuality in Asian societies for over a century. Due to the high demand, several artificial cultivation methods have been developed for their biological activities. In this study, CM was cultured on medium that contained white rice and silkworm pupae, and the levels of cordycepin and adenosine, as well as its aphrodisiac effects in diabetes-induced erectile dysfunction (DIED), were evaluated. Diabetic rats were induced by streptozotocin (STZ) injection and administered orally with CM (0.1, 0.5, and 1.0 g/kg BW/day) for 3 weeks. Diabetic rats in negative and positive control groups received vehicle and sildenafil citrate (5 mg/kg), respectively. Results showed the changes in mating behaviour in which mount latency and intromission latency were significantly increased in diabetic rats, compared with the normal control group. Diabetic rats also showed a significant reduction in intracavernosal pressure (ICP) response to cavernous nerve stimulation, sperm count, testosterone level, penile nitric oxide synthase (NOS), and testicular superoxide dismutase (SOD) activities, when compared to the normal control group. Administration of CM (0.1, 0.5, and 1.0 g/kg BW/day) reversed the effects of diabetes on the mating behaviour, and the ICP responses to electrical stimulation. Moreover, the levels of penile NOS, testicular SOD activities, testosterone, and sperm count were significantly increased, and testicular malondialdehyde (MDA) levels were significantly decreased in these treated diabetic rats. Diabetic rats treated with sildenafil showed a significant induction in intromission frequency and NOS and SOD activities, as well as a marked increase in ICP responses. These results suggest that CCM exerts its aphrodisiac effect, possibly through activating testosterone production and suppressing oxidative stress to enhance erectile function in diabetic rats.

Protective effect of wax apple (Syzygium samarangense (Blume) Merr. & L.M. Perry) against streptozotocin-induced pancreatic ß-cell damage in diabetic rats.

The purpose of this study was to investigate the protective properties and mechanisms of wax apple (Syzygium samarangense (Blume)) against streptozotocin (STZ)-induced pancreatic ß-cell apoptosis in diabetic rats. Diabetes was induced by STZ (65 mg/kg; i.p.) injection and wax apple (100 mg/kg) was orally administered to diabetic rats for a period of 30 days. During this time, fasting blood glucose (FBG) and body weight were measured weekly. At the end of the experiment, serum insulin, HOMA-B, and pancreatic insulin expression were assessed. The expression of apoptosis-related proteins along with the nitrotyrosine level, antioxidant activities, and pro-inflammatory cytokine TNF-α in the pancreas were also determined. STZ-induced diabetic rats exhibited an increase in FBG, and a decrease in body weight, serum and pancreatic insulin, as well as HOMA-B. Pancreatic apoptosis was noted in diabetic rats and indicated by enhancing the expression of cleaved caspase-3 and Bax proteins and downregulating the expression of Bcl-2 and Bcl-xl proteins. The activities of antioxidant CAT and SOD in the pancreas of the diabetic rats was also reduced. Importantly, wax apple treatment resulted in a significant reduction of FBG and increased body weight in diabetic rats. Wax apple also improved pancreatic ß-cell function, this was clearly evidenced by increased HOMA-B and pancreatic and serum insulin levels in diabetic rats. Moreover, pancreatic ß-cell apoptosis was alleviated with significantly down-regulated cleaved caspase-3 and Bax protein expression, and upregulated Bcl-2 and Bcl-xl protein expression in wax apple treated diabetic rats. These were related to the induction of CAT and SOD activities, and reduction of nitrotyrosine and TNF-α levels in wax apple administration. Overall, these results provide evidence that wax apple protects against STZ-induced pancreatic ß-apoptosis and dysfunction in diabetic rats, possibly through inhibiting oxidative stress and pro-inflammatory cytokine, and activating anti-apoptotic proteins.

Estrogen reduces endoplasmic reticulum stress to protect against glucotoxicity induced-pancreatic ß-cell death.

Estrogen can improve glucose homeostasis not only in diabetic rodents but also in humans. However, the molecular mechanism by which estrogen prevents pancreatic ß-cell death remains unclear. To investigate this issue, INS-1 cells, a rat insulinoma cell line, were cultured in medium with either 11.1mM or 40mM glucose in the presence or the absence of estrogen. Estrogen significantly reduced apoptotic ß-cell death by decreasing nitrogen-induced oxidative stress and the expression of the ER stress markers GRP 78, ATF6, P-PERK, PERK, uXBP1, sXBP1, and CHOP in INS-1 cells after prolonged culture in medium with 40mM glucose. In contrast, estrogen increased the expression of survival proteins, including sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA-2), Bcl-2, and P-p38, in INS-1 cells after prolonged culture in medium with 40mM glucose. The cytoprotective effect of estrogen was attenuated by addition of the estrogen receptor (ERα and ERß) antagonist ICI 182,780 and the estrogen membrane receptor inhibitor G15. We showed that estrogen decreases not only oxidative stress but also ER stress to protect against 40mM glucose-induced pancreatic ß-cell death.