Effects of Modified Sanzi Yangqin Decoction on Tyrosine Phosphorylation of IRS-1 in Skeletal Muscle of Type 2 Diabetic Rats

This study aimed to investigate the effect of Modified Sanzi Yangqin Decoction on tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) in skeletal muscle of type 2 diabetic rats. The rat model of type 2 diabetes was induced by high-fat diet and multiple low-dose streptozotocin injections. Diabetic model rats were randomly divided into 5 groups: the model control group, the metformin group, and Modified Sanzi Yangqin Decoction groups of low, medium, and high doses. OGTT was conducted every two weeks during treatment period. At the end of the treatment, the fasting blood glucose (FBG) level and the fasting C-peptide level were measured to calculate insulin resistance index. The levels of IRS-1, p-IRS-1Tyr895, and protein tyrosine phosphates 1B (PTP1B) in skeletal muscle were also measured. Modified Sanzi Yangqin Decoction significantly reduced the FBG level, increased the fasting C-peptide level, and lowered the insulin resistance index in type 2 diabetic rats. It also significantly increased the protein level of p-IRS-1Tyr895 and reduced the PTP1B protein level in skeletal muscle of type 2 diabetic rats. Modified Sanzi Yangqin Decoction increases tyrosine phosphorylation of IRS-1 in skeletal muscle of type 2 diabetic rats, which results from the increase of p-IRS-1Tyr895 protein and is related to the suppression of PTP1B protein.

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SUN-656 Hypoglycemic Effect of Oral Administered Superoxide Dismutase

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.875 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Shutao Liu ◽

Hangqi Liu

Keyword(s):

Insulin Resistance ◽

Superoxide Dismutase ◽

Resistance Index ◽

Diabetic Rats ◽

Hypoglycemic Effect ◽

Model Group ◽

Curative Effect ◽

Insulin Resistance Index ◽

Type 2 Diabetic

Abstract Hypoglycemic Effect of Oral Administered Superoxide Dismutase on Type 2 Diabetes via reduction of glucogan and insulin resistance Background & Objective: Superoxide dismutase (SOD) is carefully used in food industry for the concern of its easy degradation and difficult adsorption in digestive tract, although it plays central role in antioxidant system. It is previous reported that orally administered SOD was effective in alleviating hyperglycemia, cerebral ischemia-reperfusion and chronic hepatitis. This work aimed to investigate in-depth the hypoglycaemic effect and possible mechanism of orally administered SOD in the model of type 2 diabetic rats. Methods:The model of type 2 diabetic rats were divided into 6 groups and orally administered with different Cu/Zn-SOD (abbreviated as SOD) samples and negative or positive controls. The 6 groups included SOD, SOD hydrolysate (pepsin-treated SOD), L-SOD (liposome-embedded SOD), model group and metformin positive groups, as well as normal group. Results of the body weight, serum indexes (including blood glucose, glycated albumin, insulin, glucagon, AMPK, MDA), SOD enzymatic activity in organs (liver, heart, kidney, skeletal muscle, spleen, and pancreas) as well as intestinal density and HE staining were measured to evaluate the hypoglycemic effect and possible mechanism. Results: SOD showed substantial hypoglycemic effect and improved serum indicators. Moreover, L-SOD group exhibited better effect than SOD group, though the effect of SOD hydrolysate was not obvious. Colon density and HE staining showed obvious intestinal injury in the model group, and SOD was beneficial to repair intestinal structural integrity. Furthermore, the reparative effect of SOD was much better than that of the SOD hydrolysate, but not as good as that of the L-SOD. The SOD enzymatic activity of tissues was positively correlated with the curative effect of three kinds of SOD samples. The contents of serum MDA were negatively correlated with the curative effect. Compared with the model group, the insulin resistance index of SOD group, L-SOD group and positive group were significantly reduced; and glucagon significantly decreased by 68.38, 77.50 and 65.01%, respectively. Conclusion: Oral SOD showed obvious hypoglycemic effect on type 2 diabetic rats, and liposome could improve this effect. The mechanism may be that SOD effectively reduces intestinal injury, so as to reduce glucongen and insulin resistance index.

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Alteration of the intestinal barrier and GLP2 secretion in Berberine-treated type 2 diabetic rats

Journal of Endocrinology ◽

10.1530/joe-13-0184 ◽

2013 ◽

Vol 218 (3) ◽

pp. 255-262 ◽

Cited By ~ 27

Author(s):

C Y Shan ◽

J H Yang ◽

Y Kong ◽

X Y Wang ◽

M Y Zheng ◽

...

Keyword(s):

Insulin Resistance ◽

Intestinal Barrier ◽

Resistance Index ◽

Diabetic Rats ◽

Diabetic Patients ◽

Sprague Dawley ◽

Type 2 Diabetic Patients ◽

Junction Protein ◽

Type 2 Diabetic

For centuries, Berberine has been used in the treatment of enteritis in China, and it is also known to have anti-hyperglycemic effects in type 2 diabetic patients. However, as Berberine is insoluble and rarely absorbed in gastrointestinal tract, the mechanism by which it works is unclear. We hypothesized that it may act locally by ameliorating intestinal barrier abnormalities and endotoxemia. A high-fat diet combined with low-dose streptozotocin was used to induce type 2 diabetes in male Sprague Dawley rats. Berberine (100 mg/kg) was administered by lavage to diabetic rats for 2 weeks and saline was given to controls. Hyperinsulinemia and insulin resistance improved in the Berberine group, although there was no significant decrease in blood glucose. Berberine treatment also led to a notable restoration of intestinal villi/mucosa structure and less infiltration of inflammatory cells, along with a decrease in plasma lipopolysaccharide (LPS) level. Tight junction protein zonula occludens 1 (ZO1) was also decreased in diabetic rats but was restored by Berberine treatment. Glutamine-induced glucagon-like peptide 2 (GLP2) secretion from ileal tissue decreased dramatically in the diabetic group but was restored by Berberine treatment. Fasting insulin, insulin resistance index, plasma LPS level, and ZO1 expression were significantly correlated with GLP2 level. In type 2 diabetic rats, Berberine treatment not only augments GLP2 secretion and improves diabetes but is also effective in repairing the damaged intestinal mucosa, restoring intestinal permeability, and improving endotoxemia. Whether these effects are mechanistically related will require further studies, but they certainly support the hypothesis that Berberine acts via modulation of intestinal function.

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Gymnemic acid, a potent antidiabetic agent protects skeletal muscle from hyperglycemia mediated oxidative stress and apoptotic events in High fat and High fructose diet fed adult rats

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i2.2029 ◽

2020 ◽

Vol 11 (2) ◽

pp. 1526-1538

Author(s):

Porkodi Karthikeyan ◽

Lakshmi Narasimhan Chakrapani ◽

Thangarajeswari Mohan ◽

Bhavani Tamilarasan ◽

Pughazhendi Kannan ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Skeletal Muscle ◽

Diabetic Rats ◽

High Fat ◽

Gymnemic Acid ◽

High Fructose ◽

Type 2 Diabetic

Type 2 diabetes is delineated by impaired metabolic flexibility, and intramyocellular lipid accumulation, causing insulin resistance, particularly in skeletal muscle by reducing insulin-stimulated glucose uptake. High-fat diet and high fructose (HFD and HF) administration in rodents bestows a model for hyperlipidemia, insulin resistance, and Type 2 diabetes. The current study is focused on elucidating the role of Gymnemic acid in combating hyperglycemia mediated oxidative stress and apoptotic events in the skeletal muscle of HFD and HF induced Type 2 diabetes in Wistar albino rats by boosting antioxidant defense system. Gymnemic acid, a saponin of triterpene glycoside contained in leaves of Gymnema Sylvestre, has potent anti-diabetic properties. Treatment with Gymnemic acid restored the antioxidant status (Gpx, SOD, CAT, GR, Vit C & Vit E) with significant (p<0.05) decrease in free radical levels and reinvigorated the expression of apoptotic and antiapoptotic proteins in Type 2 diabetic rats. Histopathological data demonstrate that oral administration of Gymnemic acid protects skeletal muscle fibers from an oxidative niche in HFD and HF in Type 2 diabetic rats. In accordance with this, Gymnemic acid might be regarded as a promising therapeutic agent against Type 2 diabetes, thereby restoring skeletal muscle integrity and function.

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