scholarly journals Supplementation with Nicotinamide Riboside Reduces Brain Inflammation and Improves Cognitive Function in Diabetic Mice

2019 ◽  
Vol 20 (17) ◽  
pp. 4196 ◽  
Author(s):  
Hee Jae Lee ◽  
Soo Jin Yang

The purpose of this study is to investigate whether nicotinamide riboside (NR) can improve inflammation and cognitive function in diabetic mice. ICR male mice were fed for 14 weeks with either high-fat chow diet (HF, 60% kcal fat) or standard chow diet (CON, 10% kcal fat). HF, streptozotocin, and nicotinamide were used to induce hyperglycemia. NR or vehicle was delivered via stomach gavage for six weeks. Oral glucose tolerance test, Y-maze test, and nest construction test were conducted before and after the NR treatment period. NR treatment induced down-regulation of NLRP3, ASC, and caspase-1. NR reduced IL-1 expression significantly by 50% in whole brains of hyperglycemic mice. Other inflammatory markers including TNF-α and IL-6 were also attenuated by NR. Brain expression of amyloid-β precursor protein and presenilin 1 were reduced by NR. In addition, NR induced significant reduction of amyloid-β in whole brains of diabetic mice. NR treatment restored hyperglycemia-induced increases in brain karyopyknosis to the levels of controls. Nest construction test showed that NR improved hippocampus functions. Spatial recognition memory and locomotor activity were also improved by NR supplementation. These findings suggest that NR may be useful for treating cognitive impairment by inhibiting amyloidogenesis and neuroinflammation.

1997 ◽  
Vol 273 (2) ◽  
pp. R725-R730 ◽  
Author(s):  
B. E. Levin ◽  
A. A. Dunn-Meynell ◽  
B. Balkan ◽  
R. E. Keesey

In outbred Sprague-Dawley rats, about one-half develop diet-induced obesity (DIO) on a diet relatively high in fat and energy (HE diet). The rest are diet resistant (DR), gaining weight and fat at the same rate as chow-fed controls. Here we selectively bred for high (DIO) and low (DR) weight gainers after 2 wk on HE diet. By the F5 generation, both male and female inbred DIO rats gained > 90% more weight than inbred DR rats on HE diets. Even on low-fat chow diet, DIO males were 31% and females were 22% heavier than their respective DR rats. Full metabolic characterization in male rats showed that weight-matched, chow-fed DIO-prone rats had similar energy intakes and feed efficiency [body weight (kg0.75)/energy intake (kcal)] but 44% more carcass fat than comparable DR-prone rats. Their basal plasma insulin and glucose levels in the fed state were 70 and 14% higher, respectively. But, when fasted, DIO-prone oral glucose tolerance results were comparable to DR-prone rats. Chow-fed DIO-prone males also had 42% greater 24-h urine norepinephrine levels than DR-prone males. During 2 wk on HE diet, DIO rats ate 25% more, gained 115% more weight, had 36% more carcass fat, and were 42% more feed efficient than comparable DR rats. Fasted HE diet-fed DIO rats developed frank glucose intolerance during a glucose tolerance test with 55 and 158% greater insulin and glucose areas under the curve, respectively. Thus the DIO and DR traits in the outbred Sprague-Dawley population appear to be due to a polygenic pattern of inheritance.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Yosef Eshetie Amare

Background. Diabetes mellitus is one of the leading public health problems globally, and its prevalence is increasing in Ethiopia. The current drugs for people with diabetes are costly, less effective, and less safe with a challenging administration method. Thus, globally, the need for alternative herbal antidiabetic medicines is increasing. In the previous studies, antioxidant activities have been seen in crude extracts of M. africana leaves, which is an auspicious sign of antidiabetic property. Accordingly, this study has evaluated the antidiabetic and antidyslipidemic activities of methanolic extract of M. africana leaves. Methods. Hypoglycemic and antihyperglycemic activities of the three doses (250 mg/kg, 500 mg/kg, and 1000 mg/kg) of crude methanolic extract of M. africana leaf were studied on normoglycemic, oral glucose-loaded, and alloxan-induced diabetic mice models. The effect of the extract on diabetic dyslipidemia, insulin and glycated hemoglobin levels, carbohydrate-metabolizing enzymes, and body weight was also studied in alloxan-induced diabetic mice. Glibenclamide (5 mg/kg) was used as a standard drug in all cases. Data analysis was carried out using mixed-design ANOVA. A P value of ≤0.05 was considered a statistically significant difference. Results. The methanolic extract of M. africana leaf did not show acute toxicity up to the dose of 5000 mg/kg and showed better glucose utilization in the oral glucose tolerance test. After 14 days of treatment, M. africana leaf extract decreased the blood glucose level, glycated hemoglobin, glucose-6-phosphatase, and fructose-1-6-bisphosphatase in diabetic mice. In contrast, it increased hexokinase and insulin levels in diabetic mice. Moreover, weight loss and dyslipidemia profiles have been corrected significantly in diabetic mice. Conclusion. M. africana leaves showed antihyperglycemic and antidyslipidemic effects in alloxan-induced diabetic mice. That suggests M. africana may be a potential treatment option for diabetes in the future. However, further molecular studies are required to analyze the mechanisms.


2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Long Cheng ◽  
Xiang-bao Meng ◽  
Shan Lu ◽  
Ting-ting Wang ◽  
Yue Liu ◽  
...  

Traditional Chinese medicines largely lack adequate and scientifically rigorous evidence regarding efficacy and functional mechanisms. The present study was aimed to confirm the hypoglycemic effect of Tangningtongluo (TNTL) formula, a traditional Chinese Miao medicine, in two animal models: high-fat diet and streptozotocin- (STZ-) induced diabetic rats and C57BL/KsJ-db/db diabetic mice. After 4 weeks, TNTL intervention in STZ-induced diabetic rats yielded in significant improvement on the glucose tolerance test. Moreover, the islet histopathology showed that oral TNTL reduced the severity of islet necrosis in pancreases tissue. Compared with diabetic controls, a 12-week TNTL treatment regimen (dosages = 0.9, 1.8, and 3.6 g/kg) in db/db mice significantly decreased fasting glucose and HbA1c. Additionally, oral glucose tolerance in TNTL-treated mice improved significantly, compared with diabetic mice receiving metformin. Finally, tissue histopathology and biochemical index evaluations revealed significant improvement in TNTL-treated mice. Taken together, our results show that TNTL exerted a strong hypoglycemic effect in two diabetic rodent animal models, preservingβ-cells in the pancreas islet and reducing the risk of diabetic retinopathy and nephropathy.


Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4020 ◽  
Author(s):  
Miguel Valdes ◽  
Fernando Calzada ◽  
Jessica Mendieta-Wejebe

Twelve terpenoids were evaluated in the treatment of type 2 diabetes mellitus: seven monoterpenes (geranyl acetate (1), geranic acid (2), citral (3), geraniol (4), methyl geranate (5), nerol (6), and citronellic acid (7)), three sesquiterpenes (farnesal (8), farnesol (9), and farnesyl acetate (10)), one diterpene (geranylgeraniol (11)), and one triterpene (squalene (12)) were selected to carry out a study on normoglycemic and streptozotocin-induced diabetic mice. Among these, 2, 3, 7, 8, 9, and 10 showed antihyperglycemic activity in streptozotocin-induced diabetic mice. They were then selected for evaluation in oral sucrose and lactose tolerance tests (OSTT and OLTT) as well as in an oral glucose tolerance test (OGTT). In the OSTT and OLTT, compounds 3, 7, 8, 9, and 10 showed a reduction in postprandial glucose peaks 2 h after a sucrose or lactose load (comparable to acarbose). In the case of the OGTT, 2, 7, 8, 9, and 10 showed a reduction in postprandial glucose peaks 2 h after a glucose load (comparable to canagliflozin). Our results suggest that the control of postprandial hyperglycemia may be mediated by the inhibition of disaccharide digestion, such as sucrose and lactose, and the regulation of the absorption of glucose. The first case could be associated with an ∝ -glucosidase inhibitory effect and the second with an inhibition of the sodium–glucose type 1 (SGLT-1) cotransporter. Finally, five acyclic terpenes may be candidates for the development and search for new α-glucosidase and SGLT-1 cotransporter inhibitors.


2008 ◽  
Vol 5 (2) ◽  
pp. 159-164 ◽  
Author(s):  
Sachin L. Badole ◽  
Naimesh M. Patel ◽  
Prasad A. Thakurdesai ◽  
Subhash L. Bodhankar

Mushrooms are low calorie food with very little fat and are highly suitable for obese persons. With no starch and very low sugars, they are the ‘delight of the diabetics’. Combination of herbal drugs (or isolated phytochemicals) is found to be beneficial in certain diseases when given along with conventional drugs. The aim of the present study was to evaluate the effects of aqueous extract ofPleurotus pulmonarius(Lentinaceae) (called as PP-aqu) and its interaction with glyburide in alloxan induced diabetic mice. The diabetic mice treated were with PP-aqu (500 mg/kg, p.o.) alone or combination with glyburide (10 mg/kg, p.o.) for 28 days. Blood samples were collected by orbital sinus puncture using heparinized capillary glass tubes and were analyzed for serum glucose on 0, 7th, 14th, 21st and 28th days. Body weights and mortality were noted during the study period. In oral glucose tolerance test (OGTT), glucose (2.5 g/kg, p.o.) was administered with either vehicle, PP-aqu alone or in combination with glyburide and serum glucose level analyzed at 0, 30, 60 and 120 min after drug administration. Administration of PP-aqu (500 mg/kg) and its combination with glyburide (10 mg/kg) significantly (P< 0.001) decreased serum glucose level in diabetic mice. In OGTT, glyburide or PP-aqu treatment alone or their combination produced significant (P< 0.001) increase in glucose threshold. Thus we suggest thatP. pulmonariusshowed potent and synergistic antihyperglycemic effect in combination with glyburide.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Neeraj Khatri ◽  
Amin Sagar ◽  
Nagesh Peddada ◽  
Vikas Choudhary ◽  
Bhupinder Singh Chopra ◽  
...  

The study aims to map plasma gelsolin (pGSN) levels in diabetic humans and mice models of type II diabetes and to evaluate the efficacy of gelsolin therapy in improvement of diabetes in mice. We report that pGSN values decrease by a factor of 0.45 to 0.5 in the blood of type II diabetic humans and mice models. Oral glucose tolerance test in mice models showed that subcutaneous administration of recombinant pGSN and its F-actin depolymerizing competent versions brought down blood sugar levels comparable to Sitagliptin, a drug used to manage hyperglycemic condition. Further, daily dose of pGSN or its truncated versions to diabetic mice for a week kept sugar levels close to normal values. Also, diabetic mice treated with Sitagliptin for 7 days, showed increase in their pGSN values with the decrease in blood glucose as compared to their levels at the start of treatment. Gelsolin helped in improving glycemic control in diabetic mice. We propose that gelsolin level monitoring and replacement of F-actin severing capable gelsolin(s) should be considered in diabetic care.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Ji-Yin Zhou ◽  
Shi-Wen Zhou ◽  
Sheng-Ya Zeng ◽  
Jian-Yun Zhou ◽  
Ming-Jin Jiang ◽  
...  

The present study investigated the insulin sensitivity, hypoglycemic, and hypolipidemic activities of ethanolic extract ofMirabilis jalapaL. root (EEM) in normal and diabetic mice. After induction of diabetes with streptozotocin, both normal and diabetic mice were singly or repeatedly for 28 days administrated with EEM at doses of 2, 4, 8 g/kg, respectively. Before induction of diabetes, mice were administrated with EEM at doses of 2, 4, 8 g/kg for 14 days and were injected with streptozotocin and continued on EEM administration for another 28 days. Both after and before induction of diabetes, repeated administration with 4, 8 g/kg EEM continually lowered blood glucose level, decreased serum insulin level and improved insulin sensitivity index, and lowered serum total cholesterol, triglyceride levels and triglyceride content in liver and skeletal muscle, and increased glycogen content in these tissues; but repeated administration had no influence on those indexes of normal mice. Single administration with EEM (4, 8 g/kg) showed hypoglycemic effect in oral glucose tolerance test in normal and diabetic mice. Single administration with EEM had no hypoglycemic and hypolipidemic effects on normal and diabetic mice. These results suggest that EEM possesses both potential insulin sensitivity, hypoglycemic, and hypolipidemic effects on diabetes.


2005 ◽  
Vol 11 ◽  
pp. 28
Author(s):  
Fanny Rodriguez Vallejo ◽  
Juan Manuel Rios Torres ◽  
Francisco J. Gomez-Pérez ◽  
Juan A. Rull Rodrigo ◽  
Bernardo Pérez Enriquez

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