Unlock the Thermogenic Potential of Adipose Tissue: Pharmacological Modulation and Implications for Treatment of Diabetes and Obesity

Abstract Purpose: The aim of this study is; To examine the destruction of insulin receptor substrate-1 (IRS-1) molecule, which is one of the mechanisms that cause insulin resistance in diabetes and obesity, and its effect to reduce this destruction. For this purpose, the effects of exercise, metformin, exenatide and pioglitazone treatments on IRS-1 ubiquitination in pancreas, muscle and adipose tissue were investigated in an obese and diabetic animal model. Method: Obese rat model was used in this study. This model is characterised by obesity, diabetes and insulin resistance. This study investigated the molecular mechanisms of IRS-1 breakdown in diabetes. IRS1, SOCS1, SOC3 expressions were evaluated in the liver, muscle and adipose tissue of this model. At the same time, immunohistochemical analyses were performed in terms of IRS1, SOCS1 and SOCS3 in the same tissues. Results: Gene expression and Immunohistochemical analysis results were evaluated, the increase in IRS1 was noticeable in rats treated with exenatide, especially in the liver tissue despite the greater decrease in SOCS1 (P> 0.05). It was determined that other drugs in this study and used in the treatment of diabetes may also affect this mechanism to different degrees. Conclusion: Our findings showed that some drugs used in the treatment of diabetes may alter the SOCS effect and / or proteasomal degradation of the IRS-1 protein. This effect was particularly pronounced in liver tissue. However, more comprehensive studies are required to show the contribution of ubiquitination in the destruction of IRS-1 and which drugs are effective on this mechanism. Acknowledgement: This study was supported by the Scientific And Tecnological Research Council Of Turkey (TÜBİTAK) Project No: 217S089

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Adipose tissue development and lipid metabolism in the human fetus: The 2020 perspective focusing on maternal diabetes and obesity

Progress in Lipid Research ◽

10.1016/j.plipres.2020.101082 ◽

2021 ◽

Vol 81 ◽

pp. 101082

Author(s):

G. Desoye ◽

E. Herrera

Keyword(s):

Adipose Tissue ◽

Lipid Metabolism ◽

Human Fetus ◽

Maternal Diabetes ◽

Tissue Development ◽

Adipose Tissue Development ◽

Diabetes And Obesity

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Liraglutide for psychiatric disorders: clinical evidence and challenges

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2018-0031 ◽

2018 ◽

Vol 36 (2) ◽

Cited By ~ 5

Author(s):

Mehmet Akif Camkurt ◽

Luca Lavagnino ◽

Xiang Y. Zhang ◽

Antonio L Teixeira

Keyword(s):

Risk Factors ◽

Psychiatric Disorders ◽

Clinical Evidence ◽

Preclinical Studies ◽

Potential Candidate ◽

Obesity And Diabetes ◽

Treatment Of Diabetes ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Diabetes And Obesity

Abstract Obesity and diabetes are both risk factors and consequences of psychiatric disorders. Glucagon like peptide 1 (GLP-1) receptor agonists such as liraglutide are widely used in the treatment of diabetes and obesity. There are considerable amounts of preclinical studies showing the effects of liraglutide on promotion of neurogenesis, while preventing apoptosis and oxidation. Preliminary clinical evidence has suggested that liraglutide could decrease weight gain, improve cognition and prevent cognitive decline. Accordingly, liraglutide has been regarded as a potential candidate for the management of psychiatric disorders. Herein, we will discuss the association between obesity/diabetes and psychiatric disorders, and the emerging use of liraglutide in psychiatry.

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Gut as an emerging organ for the treatment of diabetes: focus on mechanism of action of bariatric and endoscopic interventions

Journal of Endocrinology ◽

10.1530/joe-17-0438 ◽

2018 ◽

Vol 237 (1) ◽

pp. R1-R17 ◽

Cited By ~ 11

Author(s):

Martin Haluzík ◽

Helena Kratochvílová ◽

Denisa Haluzíková ◽

Miloš Mráz

Keyword(s):

Type 2 Diabetes ◽

Bariatric Surgery ◽

Therapeutic Option ◽

Gastrointestinal Hormones ◽

Less Invasive ◽

Treatment Of Diabetes ◽

Endoscopic Methods ◽

Diabetes And Obesity

Increasing worldwide prevalence of type 2 diabetes mellitus and its accompanying pathologies such as obesity, arterial hypertension and dyslipidemia represents one of the most important challenges of current medicine. Despite intensive efforts, high percentage of patients with type 2 diabetes does not achieve treatment goals and struggle with increasing body weight and poor glucose control. While novel classes of antidiabetic medications such as incretin-based therapies and gliflozins have some favorable characteristics compared to older antidiabetics, the only therapeutic option shown to substantially modify the progression of diabetes or to achieve its remission is bariatric surgery. Its efficacy in the treatment of diabetes is well established, but the exact underlying modes of action are still only partially described. They include restriction of food amount, enhanced passage of chymus into distal part of small intestine with subsequent modification of gastrointestinal hormones and bile acids secretion, neural mechanisms, changes in gut microbiota and many other possible mechanisms underscoring the importance of the gut in the regulation of glucose metabolism. In addition to bariatric surgery, less-invasive endoscopic methods based on the principles of bariatric surgery were introduced and showed promising results. This review highlights the role of the intestine in the regulation of glucose homeostasis focusing on the mechanisms of action of bariatric and especially endoscopic methods of the treatment of diabetes. A better understanding of these mechanisms may lead to less invasive endoscopic treatments of diabetes and obesity that may complement and widen current therapeutic options.

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Brown Adipose Tissue and Its Implications for Diabetes and Obesity

RSSDI Diabetes Update 2016 ◽

10.5005/jp/books/13026_8 ◽

2017 ◽

pp. 27-27

Author(s):

Krishna Seshadri

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Brown Adipose ◽

Diabetes And Obesity

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Determinants and correlates of adipose tissue insulin resistance index in Japanese women without diabetes and obesity

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001686 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001686

Author(s):

Kaori Kitaoka ◽

Ayaka Tsuboi ◽

Satomi Minato-Inokawa ◽

Mari Honda ◽

Mika Takeuchi ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Young Women ◽

Fat Mass ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Japanese Women ◽

Apolipoprotein A1 ◽

Middle Aged ◽

Diabetes And Obesity

IntroductionDeterminants and correlates of a novel index of adipose tissue insulin resistance (AT-IR) (the product of fasting insulin and free fatty acid concentrations) were investigated in Japanese women without diabetes and obesity.Research design and methodsCross-sectional associations of AT-IR with fat mass and distribution, and IR-related cardiometabolic variables were examined in 210 young and 148 middle-aged women whose average body mass index (BMI) was <23 kg/m2 and waist was <80 cm. Multivariate linear regression analyses were used to identify most important determinants of AT-IR.ResultsYoung and middle-aged women did not differ in AT-IR (3.5±2.7 and 3.2±2.1, respectively). In both young and middle-aged women, AT-IR was positively associated with trunk/leg fat ratio, a sophisticated measure of abdominal fat accumulation, fasting plasma glucose (FPG), fasting triglycerides (FTG), serum alanine aminotransferase and γ-glutamyl-transpeptidase (all p<0.05). Furthermore, in middle-aged but not in young women, AT-IR showed positive associations with BMI, waist, fat mass index, low-density lipoprotein cholesterol, apolipoprotein B and systolic and diastolic blood pressure (BP) (all p<0.05). AT-IR showed no association with hemoglobin A1c, high-density lipoprotein (HDL) cholesterol and apolipoprotein A1 in two groups of women. On multivariate analysis including waist, FPG, FTG, HDL cholesterol and systolic BP as independent variables, FPG, FTG and HDL cholesterol emerged as independent determinants of AT-IR in young women (cumulative R2=0.141) and waist in middle-aged women (cumulative R2=0.056). In a model which included trunk/leg fat ratio instead of waist, trunk/leg fat ratio and systolic BP were determinants of AT-IR in middle-aged women (cumulative R2=0.093). Results did not alter in young women.ConclusionsAT-IR may be a simple and useful surrogate index of adipose tissue insulin resistance even in populations without diabetes and obesity.

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