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Chronic diabetes extensively complicates the glucose metabolism to onset and progress the complication. Concurrently, several contemporary medicines, especially organo-metallic formulations, are emerging to treat hyperglycemia. The current study aims to emphasize the gold nanoparticles (GNPs) potential for glucose metabolism regulation in Streptozotocin (STZ) induced diabetes. Quantitative real-time polymerase chain reaction (RT-PCR) was carried out to detect the mRNA expression of Glucose transporters 2 (GLUT2), Glucokinase (GK) and Glucose 6 Phosphatase (G-6-Pase). The study shows remarkable results such as the prognostic effect of GNPs in reinforcing the repression of enzyme complex G-6-Pase about 13.3-fold when compared to diabetes control. Also, molecular docking studies showed significant inhibition of G-6-Pase by the terpenoid ligands with alpha and beta amyrin from leaf extract of Couroupita guianensis. Thus the study explored the novel mechanism of G-6-Pase downregulated by GNPs intervention that majorly contributes to the regulation of circulatory glucose homeostasis during diabetes.

Chronic diabetes extensively complicates the glucose metabolism to onset and progress the complication. Concurrently, several contemporary medicines, especially organo-metallic formulations, are emerging to treat hyperglycemia. The current study aims to emphasize the gold nanoparticles (GNPs) potential for glucose metabolism regulation in Streptozotocin (STZ) induced diabetes. Quantitative real-time polymerase chain reaction (RT-PCR) was carried out to detect the mRNA expression of Glucose transporters 2 (GLUT2), Glucokinase (GK) and Glucose 6 Phosphatase (G-6-Pase). The study shows remarkable results such as the prognostic effect of GNPs in reinforcing the repression of enzyme complex G-6-Pase about 13.3-fold when compared to diabetes control. Also, molecular docking studies showed significant inhibition of G-6-Pase by the terpenoid ligands with alpha and beta amyrin from leaf extract of Couroupita guianensis. Thus the study explored the novel mechanism of G-6-Pase downregulated by GNPs intervention that majorly contributes to the regulation of circulatory glucose homeostasis during diabetes. [ABSTRACT FROM AUTHOR]

De novo hepatic glucose production or hepatic gluconeogenesis is the main contributor to hyperglycemia in the fasting state in patients with type 2 diabetes (T2D) owing to insulin resistance, which leads to at least twice as much glucose synthesis compared to healthy subjects. Therefore, control of this pathway is a promising target to avoid the chronic complications associated with elevated glucose levels. Patients with T2D in the rural communities of Mexico use medicinal plants prepared as infusions that are consumed over the day between meals, thus following this rationale (consumption of the infusions in the fasting state), one approach to understanding the possible mechanism of action of medicinal plants is to assess their capacity to inhibit hepatic glucose production. Furthermore, in several of these plants, the presence of phenolic acids able to block the enzyme glucose-6-phosphatase (G6Pase) is reported. In the present work, extracts of Ageratina petiolaris, Bromelia karatas, Equisetum myriochaetum, Rhizophora mangle, and Smilax moranensis, which are Mexican plants that have been traditionally used to treat T2D, were assayed to evaluate their possible hepatic glucose output (HGO) inhibitory activity with a pyruvate tolerance test in 18-h fasted STZ-NA Wistar rats after oral administration of the extracts. In addition, the in vitro effects of the extracts on the last HGO rate-limiting enzyme G6Pase was analyzed. Our results showed that four of these plants had an effect on hepatic glucose production in the in vivo or in vitro assays. A. petiolaris and R. mangle extracts decreased glucose output, preventing an increase in the blood glucose levels and sustaining this prevented increase after pyruvate administration. Moreover, both extracts inhibited the catalytic activity of the G6Pase complex. On the other hand, even though S. moranensis and B. karatas did not exhibit a significant in vivo effect, S. moranensis had the most potent inhibitory effect on this enzymatic system, while the E. myriochaetum extract only inhibited hepatic glucose production in the pyruvate tolerance test. Because of the traditional method in which diabetic patients use plants, hepatic glucose production inhibition seems to be a mechanism that partially explains the common hypoglycemic effect. However, further studies must be carried out to characterize other mechanisms whereby these plants can decrease HGO.

De novo hepatic glucose production or hepatic gluconeogenesis is the main contributor to hyperglycemia in the fasting state in patients with type 2 diabetes (T2D) owing to insulin resistance, which leads to at least twice as much glucose synthesis compared to healthy subjects. Therefore, control of this pathway is a promising target to avoid the chronic complications associated with elevated glucose levels. Patients with T2D in the rural communities of Mexico use medicinal plants prepared as infusions that are consumed over the day between meals, thus following this rationale (consumption of the infusions in the fasting state), one approach to understanding the possible mechanism of action of medicinal plants is to assess their capacity to inhibit hepatic glucose production. Furthermore, in several of these plants, the presence of phenolic acids able to block the enzyme glucose-6-phosphatase (G6Pase) is reported. In the present work, extracts of Ageratina petiolaris , Bromelia karatas , Equisetum myriochaetum , Rhizophora mangle , and Smilax moranensis , which are Mexican plants that have been traditionally used to treat T2D, were assayed to evaluate their possible hepatic glucose output (HGO) inhibitory activity with a pyruvate tolerance test in 18-h fasted STZ-NA Wistar rats after oral administration of the extracts. In addition, the in vitro effects of the extracts on the last HGO rate-limiting enzyme G6Pase was analyzed. Our results showed that four of these plants had an effect on hepatic glucose production in the in vivo or in vitro assays. A. petiolaris and R. mangle extracts decreased glucose output, preventing an increase in the blood glucose levels and sustaining this prevented increase after pyruvate administration. Moreover, both extracts inhibited the catalytic activity of the G6Pase complex. On the other hand, even though S. moranensis and B. karatas did not exhibit a significant in vivo effect, S. moranensis had the most potent inhibitory effect on this enzymatic system, while the E. myriochaetum extract only inhibited hepatic glucose production in the pyruvate tolerance test. Because of the traditional method in which diabetic patients use plants, hepatic glucose production inhibition seems to be a mechanism that partially explains the common hypoglycemic effect. However, further studies must be carried out to characterize other mechanisms whereby these plants can decrease HGO. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the hypoglycemic effects of an ethanol extract of Cassia abbreviata (ECA) bark and the possible mechanisms of its action in diabetic albino rats. Methods: ECA was prepared by soaking the powdered plant material in 70% ethanol. It was filtered and made solvent-free by evaporation on a rotary evaporator. Type 2 diabetes was induced in albino rats by injecting 35 mg/kg body weight (bw) of streptozotocin after having fed the rats a high-fat diet for 2 weeks. Diabetic rats were divided into ECA-150, ECA-300 and Metformin (MET)-180 groups, where the numbers are the doses in mg.kg.bw administered to the groups. Normal (NC) and diabetic (DC) controls were given distilled water. The animals had their fasting blood glucose levels and body weights determined every 7 days for 21 days. Oral glucose tolerance tests (OGTTs) were carried out in all animals at the beginning and the end of the experiment. Liver and kidney samples were harvested for glucose 6 phosphatase (G6Pase) and hexokinase activity analyses. Small intestines and diaphragms from normal rats were used for α-glucosidase and glucose uptake studies against the extract. Results: Two doses, 150 and 300 mg/kg bw, significantly reduced the fasting blood glucose levels in diabetic rats and helped them maintain normal body weights. The glucose level in DC rats significantly increased while their body weights decreased. The 150 mg/kg bw dose significantly increased hexokinase and decreased G6Pase activities in the liver and the kidneys. ECA inhibited α-glucosidase activity and promoted glucose uptake in the rats’ hemi-diaphragms. Conclusion: This study revealed that ECA normalized blood glucose levels and body weights in type 2 diabetic rats. The normalization of the glucose levels may possibly be due to inhibition of α-glucosidase, decreased G6Pase activity, increased hexokinase activity and improved glucose uptake by muscle tissues.

Obesity is a notable risk factor for developing type 2 diabetes, augmenting the concern of obese diabetes (ObD). Anti-obesity and antioxidant effects of red pepper seeds extract (RPSE) have increased our expectations that RPSE would also improve the pathological phenotypes of obese diabetes. Therefore, we hypothesized that RPSE would have an anti-diabetic effect in ObD mice. Animals were assigned either as follows: (1) db/+, (2) db/db control, (3) RPSE (200 mg/kg bw), or (4) a comparative control (metformin 150 mg/kg bw). RPSE was orally administered daily for 8 weeks. As a result, RPSE supplementation improved diabetic phenotypes, including fasting glucose, hemoglobin (HbA1c), and insulin levels. Pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6), and triglycerides were reduced in RPSE-treated mice. RPSE supplementation also diminished the rate-limiting enzymes of gluconeogenesis, including glucose 6-phosphatas (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), in the liver. RPSE supplementation increased the phosphorylation of forkhead box protein O1 (FOXO1) and AMP-activated protein kinase (AMPK), which underlined the mechanism of the anti-diabetic effects of RPSE. Taken together, RPSE has the potential to improve glycemic control by repressing hepatic gluconeogenesis via the phosphorylation of FOXO1 and AMPK in ObD mice.

Liver plays a vital role in blood glucose homeostasis. Recent studies have provided considerable evidence that hepatic glucose production (HGP) plays an important role in the development of fasting hyperglycemia in diabetes. From this perspective, diminution of HGP has certainly been considered for the treatment of diabetes. In the present study, we have analyzed the modulatory effects of fisetin, a flavonoid of strawberries, on the expression of key enzymes of carbohydrate metabolism in STZ induced experimental diabetic rats. The physiological criterions such as food and fluid intake were regularly monitored. The levels of blood glucose, plasma insulin, hemoglobin and glycosylated hemoglobin were analyzed. The mRNA and protein expression levels of gluconeogenic genes such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were determined by immunoblot as well as PCR analysis. Diabetic group of rats showed significant increase in food and water intake when compared with control group of rats. Upon oral administration of fisetin as well as gliclazide to diabetic group of rats, the levels were found to be decreased. Oral administration of fisetin (10 mg/kg body weight) to diabetic rats for 30 days established a significant decline in blood glucose and glycosylated hemoglobin levels and a significant increase in plasma insulin level. The mRNA and protein expression levels of gluconeogenic genes, such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), were decreased in liver tissues upon treatment with fisetin. The results of the present study suggest that fisetin improves glucose homeostasis by direct inhibition of gluconeogenesis in liver. [ABSTRACT FROM AUTHOR]

Hepatic gluconeogenesis is a major contributing factor to hyperglycemia in the fasting and postprandial states in type 2 diabetes mellitus (T2DM). Because Sirtuin 1 (SirT1) induces hepatic glucone-ogenesis during fasting through the induction of phosphoenol-pyruvate carboxylase kinase (PEPCK), fructose-1,6-bisphosphatase (FBPase), and glucose-6-phosphatase (G6Pase) gene transcription, we hypothesized that reducing SirT1, by using an antisense oligonucleotide (ASO), would decrease fasting hyperglycemia in a rat model of T2DM. SirT1 ASO lowered both fasting glucose concentration and hepatic glucose production in the T2DM rat model. Whole body insulin sensitivity was also increased in the SirT1 ASO treated rats as reflected by a 25% increase in the glucose infusion rate required to maintain euglycemia during the hyperinsulinemic-euglycemic clamp and could entirely be attributed to increased suppression of hepatic glucose production by insulin. The reduction in basal and clamped rates of glucose production could in turn be attributed to decreased expression of PEPCK, FBPase, and G6Pase due to increased acetylation of signal transducer and activator of transcription 3 (STAT3), forkhead box O1 (FOXO1), and peroxisome proliferator-activated receptor-γ coactivator la (PGC-1α), known substrates of SirT1. In addition to the effects on glucose metabolism, SirT1 ASO decreased plasma total cholesterol, which was attributed to increased cholesterol uptake and export from the liver. These results indicate that inhibition of hepatic SirT1 may be an attractive approach for treatment of T2DM. [ABSTRACT FROM AUTHOR]

Obesity is a notable risk factor for developing type 2 diabetes, augmenting the concern of obese diabetes (ObD). Anti-obesity and antioxidant effects of red pepper seeds extract (RPSE) have increased our expectations that RPSE would also improve the pathological phenotypes of obese diabetes. Therefore, we hypothesized that RPSE would have an anti-diabetic effect in ObD mice. Animals were assigned either as follows: (1) db/+, (2) db/db control, (3) RPSE (200 mg/kg bw), or (4) a comparative control (metformin 150 mg/kg bw). RPSE was orally administered daily for 8 weeks. As a result, RPSE supplementation improved diabetic phenotypes, including fasting glucose, hemoglobin (HbA1c), and insulin levels. Pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6), and triglycerides were reduced in RPSE-treated mice. RPSE supplementation also diminished the rate-limiting enzymes of gluconeogenesis, including glucose 6-phosphatas (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), in the liver. RPSE supplementation increased the phosphorylation of forkhead box protein O1 (FOXO1) and AMP-activated protein kinase (AMPK), which underlined the mechanism of the anti-diabetic effects of RPSE. Taken together, RPSE has the potential to improve glycemic control by repressing hepatic gluconeogenesis via the phosphorylation of FOXO1 and AMPK in ObD mice. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the hypoglycemic effects of an ethanol extract of Cassia abbreviata (ECA) bark and the possible mechanisms of its action in diabetic albino rats., Methods: ECA was prepared by soaking the powdered plant material in 70% ethanol. It was filtered and made solvent-free by evaporation on a rotary evaporator. Type 2 diabetes was induced in albino rats by injecting 35 mg/kg body weight (bw) of streptozotocin after having fed the rats a high-fat diet for 2 weeks. Diabetic rats were divided into ECA-150, ECA-300 and Metformin (MET)-180 groups, where the numbers are the doses in mg.kg.bw administered to the groups. Normal (NC) and diabetic (DC) controls were given distilled water. The animals had their fasting blood glucose levels and body weights determined every 7 days for 21 days. Oral glucose tolerance tests (OGTTs) were carried out in all animals at the beginning and the end of the experiment. Liver and kidney samples were harvested for glucose 6 phosphatase (G6Pase) and hexokinase activity analyses. Small intestines and diaphragms from normal rats were used for α-glucosidase and glucose uptake studies against the extract., Results: Two doses, 150 and 300 mg/kg bw, significantly reduced the fasting blood glucose levels in diabetic rats and helped them maintain normal body weights. The glucose level in DC rats significantly increased while their body weights decreased. The 150 mg/kg bw dose significantly increased hexokinase and decreased G6Pase activities in the liver and the kidneys. ECA inhibited α -glucosidase activity and promoted glucose uptake in the rats' hemi-diaphragms., Conclusion: This study revealed that ECA normalized blood glucose levels and body weights in type 2 diabetic rats. The normalization of the glucose levels may possibly be due to inhibition of α -glucosidase, decreased G6Pase activity, increased hexokinase activity and improved glucose uptake by muscle tissues., Competing Interests: Conflict of interest The authors declare that there are no conflicts of interest.

The objective of this study was to investigate the impact of elevated tissue omega-3 (n-3) polyunsaturated fatty acids (PUFA) status on age-related glucose intolerance utilizing the fat-1 transgenic mouse model, which can endogenously synthesize n-3 PUFA from omega-6 (n-6) PUFA. Fat-1 and wild-type mice, maintained on the same dietary regime of a 10% corn oil diet, were tested at two different ages (2 months old and 8 months old) for various glucose homeostasis parameters and related gene expression. The older wild-type mice exhibited significantly increased levels of blood insulin, fasting blood glucose, liver triglycerides, and glucose intolerance, compared to the younger mice, indicating an age-related impairment of glucose homeostasis. In contrast, these age-related changes in glucose metabolism were largely prevented in the older fat-1 mice. Compared to the older wild-type mice, the older fat-1 mice also displayed a lower capacity for gluconeogenesis, as measured by pyruvate tolerance testing (PTT) and hepatic gene expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6 phosphatase (G6Pase). Furthermore, the older fat-1 mice showed a significant decrease in body weight, epididymal fat mass, inflammatory activity (NFκ-B and p-IκB expression), and hepatic lipogenesis (acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) expression), as well as increased peroxisomal activity (70-kDa peroxisomal membrane protein (PMP70) and acyl-CoA oxidase1 (ACOX1) expression). Altogether, the older fat-1 mice exhibit improved glucose homeostasis in comparison to the older wild-type mice. These findings support the beneficial effects of elevated tissue n-3 fatty acid status in the prevention and treatment of age-related chronic metabolic diseases., (Copyright © 2013 Elsevier B.V. All rights reserved.)