scholarly journals Improvements in Insulin Resistance and β-Cells Dysfunction by DDP-4 Inhibition Potential of Withania somnifera (L.) Dunal Root Extract in Type 2 Diabetic Rat

2020 ◽  
Vol 11 (1) ◽  
pp. 8141-8155
Keyword(s):  
Insulin Resistance ◽  
Withaferin A ◽  
Root Extract ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Standard Compound ◽  
High Sucrose ◽  
Type 2 Diabetic

The study was aimed to evaluate improvements in insulin resistance and β-cell dysfunction by DPP-4 inhibition potential of W. somnifera (L.) Dunal root extract in type 2 diabetic rats. The experimental design was containing the in-vitro assay of chosen extract for DPP-4 inhibition, in-silico analysis of DPP-4 binding with dominating compound withaferin – A and in-vivo assays, respectively. Diabetes induction made through the administration of the corticosteroid [1.0 mg/Kg] and high sucrose diet, which was calculated by HOMA [Homeostasis model assessment]. Whereas the presence of the Withaferin – A (steroidal lactone) in extract (dominating compound of extract) was confirmed by HPLC isolation in comparison to the standard compound. Consequently, the histopathology of the pancreas and antioxidants of renal and hepatic tissues were assayed by standard methods. The chosen extract showed 77.3 % in-vitro DPP-4 inhibition and -9.18 to -6.16 KD binding energy performed with active sites of DPP-4. The corticosteroid and high sucrose feeding caused significant changes in HOMA-IR = 3.9 ±40 %, HOMA β % = 65.4±4.12 % and HOMA sensitivity = 25.5±1.2 %. The treatment of extract of WS altered significantly (𝑃 ≤ 0.001) to HOMA indices, HbA1c, insulin, and glucose levels. Consequently, significant changes were seen in the histology of pancreas and antioxidants levels in hepatic and renal tissues. Accordingly, the occurrence of withaferin-A was (dominating compound of extract) confirmed from HPLC isolation in comparison to the standard compound. The FT-IR spectra annotated the availability of potent functional groups in the extract. The results illustrated that amelioration of insulin resistance and β-cell dysfunction were conducted as per DPP-4 inhibition potential of W. somnifera root extract. Therefore, it can be concluded that W. somnifera root extract possesses withaferin -A like bioactive compounds having a capacity of DPP-4 inhibition, which can ameliorate insulin resistance and β-cell dysfunction.

Upregulation of PPARγ by Aegle marmelos Ameliorates Insulin Resistance and β-cell Dysfunction in High Fat Diet Fed-Streptozotocin Induced Type 2 Diabetic Rats

2011 ◽  
Vol 25 (10) ◽  
pp. 1457-1465 ◽  
Author(s):  
Ashok Kumar Sharma ◽  
Saurabh Bharti ◽  
Sameer Goyal ◽  
Sachin Arora ◽  
Saroj Nepal ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Diabetic Rats ◽  
High Fat ◽  
Aegle Marmelos ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Type 2 Diabetic

scholarly journals Up-regulation of PPARγ, heat shock protein-27 and -72 by naringin attenuates insulin resistance, β-cell dysfunction, hepatic steatosis and kidney damage in a rat model of type 2 diabetes

2011 ◽  
Vol 106 (11) ◽  
pp. 1713-1723 ◽  
Author(s):  
Ashok Kumar Sharma ◽  
Saurabh Bharti ◽  
Shreesh Ojha ◽  
Jagriti Bhatia ◽  
Narender Kumar ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Diabetic Rats ◽  
Kidney Damage ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Hsp 27 ◽  
Liver And Kidney ◽  
Type 2 Diabetic

Naringin, a bioflavonoid isolated from grapefruit, is well known to possess lipid-lowering and insulin-like properties. Therefore, we assessed whether naringin treatment ameliorates insulin resistance (IR), β-cell dysfunction, hepatic steatosis and kidney damage in high-fat diet (HFD)–streptozotocin (STZ)-induced type 2 diabetic rats. Wistar albino male rats were fed a HFD (55 % energy from fat and 2 % cholesterol) to develop IR and on the 10th day injected with a low dose of streptozotocin (40 mg/kg, intraperitoneal (ip)) to induce type 2 diabetes. After confirmation of hyperglycaemia (>13·89 mmol/l) on the 14th day, different doses of naringin (25, 50 and 100 mg/kg per d) and rosiglitazone (5 mg/kg per d) were administered orally for the next 28 d while being maintained on the HFD. Naringin significantly decreased IR, hyperinsulinaemia, hyperglycaemia, dyslipidaemia, TNF-α, IL-6, C-reactive protein and concomitantly increased adiponectin and β-cell function in a dose-dependent manner. Increased thiobarbituric acid-reactive substances and decreased antioxidant enzyme activities in the serum and tissues of diabetic rats were also normalised. Moreover, naringin robustly increased PPARγ expression in liver and kidney; phosphorylated tyrosine insulin receptor substrate 1 in liver; and stress proteins heat shock protein (HSP)-27 and HSP-72 in pancreas, liver and kidney. In contrast, NF-κB expression in these tissues along with sterol regulatory element binding protein-1c and liver X receptor- expressions in liver were significantly diminished. In addition, microscopic observations validated that naringin effectively rescues β-cells, hepatocytes and kidney from HFD-STZ-mediated oxidative damage and pathological alterations. Thus, this seminal study provides cogent evidence that naringin ameliorates IR, dyslipidaemia, β-cell dysfunction, hepatic steatosis and kidney damage in type 2 diabetic rats by partly regulating oxidative stress, inflammation and dysregulated adipocytokines production through up-regulation of PPARγ, HSP-27 and HSP-72.

scholarly journals Visceral Adiposity Index is associated with Insulin Resistance, impaired Insulin Secretion, and β-cell dysfunction in subjects at risk for Type 2 Diabetes

2021 ◽  
pp. 100013
Author(s):  
Froylan David Martínez-Sánchez ◽  
Valerie Paola Vargas-Abonce ◽  
Andrea Rocha-Haro ◽  
Romina Flores-Cardenas ◽  
Milagros Fernández-Barrio ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
At Risk ◽  
Insulin Secretion ◽  
Visceral Adiposity ◽  
Visceral Adiposity Index ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Impaired Insulin

The role of vitamin D in the development of type 2 diabetes

2021 ◽  
Vol 19 (1) ◽  
pp. 44-52
Author(s):  
A.P. Shumilov ◽  
◽  
M.Yu. Semchenkova ◽  
D.S. Mikhalik ◽  
T.G. Avdeeva ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Inverse Relationship ◽  
Biological Mechanisms ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Vitamin D Levels

Vitamin D plays an important role in decreasing the risk of developing type 2 diabetes by influencing calcium metabolism, thereby reducing β-cell dysfunction and preventing insulin resistance. The findings of research works are contradictory enough, although some of them demonstrated an inverse relationship between vitamin D levels and the incidence of type 2 diabetes. The article describes the biological mechanisms of relationships between vitamin D levels and type 2 diabetes, reviews the results of the studies conducted and summarizes the available data. Key words: vitamin D, type 2 diabetes mellitus, insulin resistance

Analysis of compensatory β-cell response in mice with combined mutations of Insr and Irs2

2007 ◽  
Vol 292 (6) ◽  
pp. E1694-E1701 ◽  
Author(s):  
Jane J. Kim ◽  
Yoshiaki Kido ◽  
Philipp E. Scherer ◽  
Morris F. White ◽  
Domenico Accili
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Cell Response ◽  
Cell Mass ◽  
Comprehensive Treatment ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Impaired Insulin

Type 2 diabetes results from impaired insulin action and β-cell dysfunction. There are at least two components to β-cell dysfunction: impaired insulin secretion and decreased β-cell mass. To analyze how these two variables contribute to the progressive deterioration of metabolic control seen in diabetes, we asked whether mice with impaired β-cell growth due to Irs2 ablation would be able to mount a compensatory response in the background of insulin resistance caused by Insr haploinsufficiency. As previously reported, ∼70% of mice with combined Insr and Irs2 mutations developed diabetes as a consequence of markedly decreased β-cell mass. In the initial phases of the disease, we observed a robust increase in circulating insulin levels, even as β-cell mass gradually declined, indicating that replication-defective β-cells compensate for insulin resistance by increasing insulin secretion. These data provide further evidence for a heterogeneous β-cell response to insulin resistance, in which compensation can be temporarily achieved by increasing function when mass is limited. The eventual failure of compensatory insulin secretion suggests that a comprehensive treatment of β-cell dysfunction in type 2 diabetes should positively affect both aspects of β-cell physiology.

scholarly journals β-Cell function or insulin resistance was associated with the risk of type 2 diabetes among women with or without obesity and a history of gestational diabetes

2020 ◽  
Vol 8 (1) ◽  
pp. e001060
Author(s):  
Yuxin Fan ◽  
Leishen Wang ◽  
Huikun Liu ◽  
Shuang Zhang ◽  
Huiguang Tian ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Diabetes Risk ◽  
Model Assessment ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Homeostatic Model Assessment ◽  
History Of ◽  
Postpartum Diabetes ◽  
Homeostatic Model

IntroductionTo evaluate the single association of postpartum β-cell dysfunction and insulin resistance (IR), as well as different combinations of postpartum β-cell dysfunction, IR, obesity, and a history of gestational diabetes mellitus (GDM) with postpartum type 2 diabetes risk.Research design and methodsThe study included 1263 women with prior GDM and 705 women without GDM. Homeostatic model assessment was used to estimate homeostatic model assessment of β-cell secretory function (HOMA-%β) and homeostatic model assessment of insulin resistance (HOMA-IR).ResultsMultivariable-adjusted ORs of diabetes across quartiles of HOMA-%β and HOMA-IR were 1.00, 1.46, 2.15, and 6.25 (ptrend <0.001), and 1.00, 2.11, 5.59, and 9.36 (ptrend <0.001), respectively. Women with IR only had the same diabetes risk as women with β-cell dysfunction only. Obesity, together with IR or β-cell dysfunction, had a stronger effect on diabetes risk. This stronger effect was also found for a history of GDM with IR or β-cell dysfunction. Women with three risk factors, including obesity, a history of GDM and β-cell dysfunction/IR, showed the highest ORs of diabetes.Conclusionsβ-cell dysfunction or IR was significantly associated with postpartum diabetes. IR and β-cell dysfunction, together with obesity and a history of GDM, had the highest ORs of postpartum diabetes risk.

scholarly journals Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients

2011 ◽  
Vol 106 (3) ◽  
pp. 383-389 ◽  
Author(s):  
Pál Brasnyó ◽  
Gergő A. Molnár ◽  
Márton Mohás ◽  
Lajos Markó ◽  
Boglárka Laczy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Cell Function ◽  
Diabetic Patients ◽  
Β Cell ◽  
Type 2 Diabetic Patients ◽  
Β Cell Function ◽  
Type 2 Diabetic

Although resveratrol has widely been studied for its potential health benefits, little is known about its metabolic effects in humans. Our aims were to determine whether the polyphenol resveratrol improves insulin sensitivity in type 2 diabetic patients and to gain some insight into the mechanism of its action. After an initial general examination (including blood chemistry), nineteen patients enrolled in the 4-week-long double-blind study were randomly assigned into two groups: a resveratrol group receiving oral 2 × 5 mg resveratrol and a control group receiving placebo. Before and after the second and fourth weeks of the trial, insulin resistance/sensitivity, creatinine-normalised ortho-tyrosine level in urine samples (as a measure of oxidative stress), incretin levels and phosphorylated protein kinase B (pAkt):protein kinase B (Akt) ratio in platelets were assessed and statistically analysed. After the fourth week, resveratrol significantly decreased insulin resistance (homeostasis model of assessment for insulin resistance) and urinary ortho-tyrosine excretion, while it increased the pAkt:Akt ratio in platelets. On the other hand, it had no effect on parameters that relate to β-cell function (i.e. homeostasis model of assessment of β-cell function). The present study shows for the first time that resveratrol improves insulin sensitivity in humans, which might be due to a resveratrol-induced decrease in oxidative stress that leads to a more efficient insulin signalling via the Akt pathway.

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