scholarly journals Selective Elevation of Adiponectin Production by the Natural Compounds Derived from a Medicinal Herb Alleviates Insulin Resistance and Glucose Intolerance in Obese Mice

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 625-633 ◽  
Author(s):  
Aimin Xu ◽  
Hongbing Wang ◽  
Ruby L. C. Hoo ◽  
Gary Sweeney ◽  
Paul. M. Vanhoutte ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Intolerance ◽  
Elevated Serum ◽  
Chronic Administration ◽  
Serum Levels ◽  
Natural Compounds ◽  
Cardiovascular Complications ◽  
Medicinal Herb ◽  
Pharmacological Intervention ◽  
Obese Mice

Adiponectin is an adipocyte-derived insulin-sensitizing hormone with antidiabetic, antiinflammatory, and antiatherosclerotic properties. A decreased serum level of adiponectin in obesity has been identified as an independent risk factor for diabetes and cardiovascular complications, suggesting that pharmacological intervention aimed at elevating adiponectin production might hold promise for the treatment and/or prevention of these diseases. Here we report the identification of two structurally related natural compounds (astragaloside II and isoastragaloside I) from the medicinal herb Radix Astragali that possess such an activity. Astragaloside II and isoastragaloside I selectively increased adiponectin secretion in primary adipocytes without any obvious effects on a panel of other adipokines. Furthermore, an additive effect on induction of adiponectin production was observed between these two compounds and rosiglitazone, a thiazolidinedione class of insulin-sensitizing drugs. Chronic administration of astragaloside II and isoastragaloside I in both dietary and genetic obese mice significantly elevated serum levels of total adiponectin and selectively increased the composition of its high molecular weight oligomeric complex. These changes were associated with an alleviation of hyperglycemia, glucose intolerance, and insulin resistance. By contrast, the beneficial effects of these two compounds on insulin sensitivity and glucose metabolism were diminished in adiponectin knockout mice. In conclusion, our results suggest that pharmacological elevation of circulating adiponectin alone is sufficient to ameliorate insulin resistance and diabetes and support the use of adiponectin as a biomarker for future drug discovery. The two natural compounds might provide the lead as a novel class of therapeutics for obesity-related diseases. Natural compounds alleviate insulin resistance by inducing adiponectin production.

scholarly journals Increased Tumor Growth in Mice with Diet-Induced Obesity: Impact of Ovarian Hormones

Endocrinology ◽  
2006 ◽  
Vol 147 (12) ◽  
pp. 5826-5834 ◽  
Author(s):  
Shoshana Yakar ◽  
Nomeli P. Nunez ◽  
Patricia Pennisi ◽  
Pnina Brodt ◽  
Hui Sun ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Tumor Growth ◽  
Glucose Intolerance ◽  
Tumor Development ◽  
Tumor Growth Rate ◽  
Obese Mice ◽  
Female Mice ◽  
Diet Induced Obesity ◽  
Body Adiposity ◽  
Obese Female

Obesity increases the risk of many cancers in both males and females. This study describes a link between obesity, obesity-associated metabolic alterations, and the risk of developing cancer in male and female mice. The goal of this study was to evaluate the relationship between gender and obesity and to determine the role of estrogen status in obese females and its effect on tumor growth. We examined the susceptibility of C57BL/6 mice to diet-induced obesity, insulin resistance/glucose intolerance, and tumors. Mice were injected sc with one of two tumorigenic cell lines, Lewis lung carcinoma, or mouse colon 38-adenocarcinoma. Results show that tumor growth rate was increased in obese mice vs. control mice irrespective of the tumor cell type. To investigate the effect of estrogen status on tumor development in obese females, we compared metabolic parameters and tumor growth in ovariectomized (ovx) and intact obese female mice. Obese ovx female mice developed insulin resistance and glucose intolerance similar to that observed in obese males. Our results demonstrate that body adiposity increased in ovx females irrespective of the diet administered and that tumor growth correlated positively with body adiposity. Overall, these data point to more rapid tumor growth in obese mice and suggest that endogenous sex steroids, together with diet, affect adiposity, insulin sensitivity, and tumor growth in female mice.

Cardioprotective and antihypertensive effects of Enicostemma littorale Blume extract in fructose-fed rats

2012 ◽  
Vol 90 (8) ◽  
pp. 1065-1073 ◽  
Author(s):  
Niraj M. Bhatt ◽  
Meenal Chavda ◽  
Dipali Desai ◽  
Rishit Zalawadia ◽  
Vaibhav B. Patel ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Vascular Reactivity ◽  
Therapeutic Potential ◽  
Serum Levels ◽  
Cardiovascular Complications ◽  
Oral Glucose ◽  
Protective Effects ◽  
High Fructose ◽  
Enicostemma Littorale ◽  
High Level

We investigated the protective effects of Enicostemma littorale Blume (EL) extract on hypertension and insulin resistance along with its associated cardiovascular complications in high fructose (HF) fed rats. For this, rats were divided among 4 groups: (i) control, fed laboratory chow; (ii) fed with a high level of fructose; (iii) fed with a high level of fructose plus E. littorale extract; and (iv) fed with a high level of fructose plus rosiglitazone (Rg). EL and Rg treatments were given simultaneously with HF diet. The results show that untreated HF-fed rats showed altered oral glucose tolerance, increased fasting insulin, and increased fasting glucose. These rats also exhibited hypertriglyceridemia, moderate hypertension, platelet hyperaggregability, decreased prothrombin time, activated partial thromboplastin time, altered vascular reactivity, and increased serum levels of enzymes (creatine kinase, type muscle–brain (CK-MB), aspartate aminotransferase (SGOT), lactate dehydrogenase (LDH), and alanine aminotransferase (SGPT). This is the first demonstration of platelet hyperaggregation and prothrombotic alteration in HF-fed rats. HF-fed rats treated with EL showed improved insulin resistance, along with reduced hypertriglyceridemia, hypertension, platelet aggregability, blood coagulation, serum enzymes (CK-MB, SGOT, LDH and SGPT), and vascular reactivity. These effects of EL in HF-induced hypertensive rats might be associated with the suppression of hyperinsulinemia and hypertriglyceridemia, along with its antiatherogenic and antithrombogenic potential. These data indicate that the aqueous extract of EL has great therapeutic potential for the prevention and (or) management of insulin resistance and the associated hypertension.

scholarly journals Surgical Remission of Acromegaly Resolves Neuroglycopenia and Paradoxical Rise in GH after OGTT

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A613-A613
Author(s):  
Maria Magar ◽  
John Carmichael
Keyword(s):  
Insulin Resistance ◽  
Elevated Serum ◽  
Serum Levels ◽  
Gastric Surgery ◽  
Mri Imaging ◽  
Low Carbohydrate Diet ◽  
Reactive Hypoglycemia ◽  
Patient Reported ◽  
Patients With Diabetes ◽  
One Year

Abstract Background: Acromegaly is known to cause insulin resistance through increased gluconeogenesis and reduction in peripheral glucose use; however, hypoglycemia related to acromegaly has not been reported. Clinical Case: A 58-year old man presented for evaluation of several elevated serum IGF1 levels. The patient had reported years of increased body heat but no changes in his hands or feet and no voice deepening. He recently needed 15 dental crowns due to gaps in his teeth. He also had difficult to manage OSA and weight gain. The patient reported neuroglycopenia after a high glycemic meal or drink, although he was never able to objectively measure any low blood glucoses when they occurred; these symptoms improved but did not resolve despite adhering to a low carbohydrate diet. He also had decreased libido and erectile dysfunction. Exam was significant for coarse facial features. Prior testing revealed several elevated IGF1 serum levels, the last one being 227 ng/mL (54-194). One year prior, OGTT resulted in an initial GH level of 0.1 ng/mL with a decrease to <0.1 ng/mL after two hours. Repeat OGTT had an initial GH of 2.98 ng/mL which paradoxically rose to 12 ng/mL. Fasting BG was 90 mg/dL and peaked at 171 mg/dL. Pituitary MRI showed a 5 mm microadenoma, consistent with acromegaly from a GH secreting adenoma. He underwent a TSSC, and his heat intolerance, low libido, and symptom of hypoglycemia resolved completely. Subsequent IGF1 levels and MRI imaging normalized. Postoperatively OGTT showed a peak GH of 0.23 ng/mL with a peak glucose of 134 mg/dL. There was no paradoxical rise in GH. Discussion: Acromegaly is commonly associated with insulin resistance in ~30% of cases; however, there are no reports of associated neuroglycopenia after a carbohydrate-rich meal or OGTT, which in our patient resolved after successful removal of the pituitary microadenoma. His low glucose symptoms could have been a result of reactive hypoglycemia, which is often seen in patients with diabetes or even prediabetes. However this patient had no history of either. He did not have evidence of any tumors causing hypoglycemia and no gastric surgery to suggest a related etiology (e.g, dumping syndrome or nesidioblastosis). Conversely since GH is normally anabolic and stimulates insulin release, the patient’s elevated GH may have caused an abnormal increase in insulin, leading to his hypoglycemia symptoms. Indeed GIP, which stimulates insulin, is thought to be the cause of the paradoxical rise in GH seen in 30% of acromegaly cases. Remarkably, the patient’s hypoglycemia symptoms disappeared after treatment of the acromegaly, which leads us to consider that excess GH was the culprit.

scholarly journals In Utero Nutritional Manipulation Provokes Dysregulated Adipocytokines Production in F1 Offspring in Rats

Scientifica ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-9
Author(s):  
Mervat Y. Hanafi ◽  
Mohamed I. Saad ◽  
Taha M. Abdelkhalek ◽  
Moustafa M. Saleh ◽  
Maher A. Kamel
Keyword(s):  
Insulin Resistance ◽  
Maternal Obesity ◽  
Control Diet ◽  
Elevated Serum ◽  
Adult Life ◽  
Serum Levels ◽  
Low Grade ◽  
Inflammatory State ◽  
Diabetes And Obesity

Background. Intrauterine environment plays a pivotal role in the origin of fatal diseases such as diabetes. Diabetes and obesity are associated with low-grade inflammatory state and dysregulated adipokines production. This study aims to investigate the effect of maternal obesity and malnutrition on adipokines production (adiponectin, leptin, and TNF-α) in F1 offspring in rats.Materials and Methods. Wistar rats were allocated in groups: F1 offspring of control mothers under control diet (CF1-CD) and under high-fat diet (CF1-HCD), F1 offspring of obese mothers under CD (OF1-CD) and under HCD (OF1-HCD), and F1 offspring of malnourished mothers under CD (MF1-CD) and under HCD (MF1-HCD). Every 5 weeks postnatally, blood samples were obtained for biochemical analysis.Results. At the end of the 30-week follow-up, OF1-HCD and MF1-HCD exhibited hyperinsulinemia, moderate dyslipidemia, insulin resistance, and impaired glucose homeostasis compared to CF1-CD and CF1-HCD. OF1-HCD and MF1-HCD demonstrated low serum levels of adiponectin and high levels of leptin compared to CF1-CD and CF1-HCD. OF1-CD, OF1-HCD, and MF1-HCD had elevated serum levels of TNF-αcompared to CF1-CD and CF1-HCD (p<0.05).Conclusion. Maternal nutritional manipulation predisposes the offspring to development of insulin resistance in their adult life, probably via instigating dysregulated adipokines production.

Elevated Serum Levels of Interleukin-18 Are Associated with Insulin Resistance in Women with Polycystic Ovary Syndrome

Endocrine ◽  
2006 ◽  
Vol 29 (3) ◽  
pp. 419-424 ◽  
Author(s):  
Yi-fei Zhang ◽  
Yi-sheng Yang ◽  
Jie Hong ◽  
Wei-qiong Gu ◽  
Chun-fang Shen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Elevated Serum ◽  
Serum Levels ◽  
Interleukin 18 ◽  
Ovary Syndrome

scholarly journals DNAJB3 Deficiency Exacerbates Diet-Induced Obesity and Insulin Resistance

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1235-1235
Author(s):  
Shadi Nejat ◽  
Shane Scoggin ◽  
Kalhara Menikdiwela ◽  
Naima Moustaid-Moussa ◽  
Aliyah Efotte ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Glucose Intolerance ◽  
Fat Mass ◽  
Biomedical Research ◽  
Mrna Levels ◽  
Obese Mice ◽  
Wild Type ◽  
Male And Female ◽  
Muscle Tissues

Abstract Objectives The prevalence of obesity and Type 2 Diabetes (T2D) continues to rise worldwide, leading to many other chronic diseases and imposing a large economic burden. DNAJ, also known as HSP40 (Heat Shock Protein-40), subfamily B, member 3 (DNAJB3), is a chaperone protein that can be induced under various stressors. Recent reports implicated DNAJB3 in protection against obesity and T2D. Specifically, DNAJB3 was downregulated in some patients with obesity and T2D; however, precise underlying mechanisms remained unclear. We hypothesized that lack of DNAJB3 will increase body weight and body fat, inflammation, glucose intolerance and insulin resistance in diet-induced obese mice, compared to B6 wild type (WT) littermates fed the same diets. Methods Three DNAJB3 knockout (KO) mutant lines were generated at the Pennington Biomedical Research Center (KO 30, 44 and 47). Male and female KO and wild type (WT) littermates were fed a high fat diet (45% kcal fat) for 12 weeks. Body weight and composition were measured weekly, and a glucose tolerance test (GTT) was conducted. Following euthanasia, blood, adipose and muscle tissues were harvested and used for serum analyses and tissue gene/protein expression, respectively. Results Compared to WT, only DNAJB3 KO male and female mice of line 47 demonstrated significantly higher body weight and fat mass (P &lt; 0.05). Similarly, line 47 also showed a lower rate of glucose clearance as measured by GTT. Consistent with increased body weight and fat mass, male mice in line 47 also exhibited significantly higher mRNA levels of inflammatory markers including TNFα and IL-1β, in gonadal fat, compared to WT and lines 30 and 44. Moreover, similar trends towards increased TNF-α and MCP-1 expression was observed in muscle tissues of KO males of line 47, when compared to WT (P &lt; 0.47), and line 30 (P &lt; 0.15) respectively. Conclusions Absence of DNAJB3, increases adiposity, glucose intolerance and inflammation in diet-induced obese mice in both males and females. these findings suggest that DNAJB3 plays an important role in metabolic functions and glucose homeostasis, which warrants further research as a potential therapeutic target for obesity and T2D. Funding Sources Funded by Qatar National Research Funds, Hamad Bin Khalifa University & Qatar Biomedical Research Institute, Qatar.

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