Role of probiotics in the prevention and management of diabetes and obesity

2022 ◽  
pp. 321-336
Author(s):  
Rashmi Hogarehalli Mallappa ◽  
Chandrasekhar Balasubramaniam ◽  
Monica Rose Amarlapudi ◽  
Shweta Kelkar ◽  
Gbenga Adedeji Adewumi ◽  
...  
Keyword(s):  
Diabetes And Obesity

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

2018 ◽  
Vol 237 (1) ◽  
pp. R1-R17 ◽  
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.

scholarly journals Macrocyclic Peptides as Allosteric Inhibitors of Nicotinamide N-Methyltransferase (NNMT)

2020 ◽  
Author(s):  
Matthijs J. van Haren ◽  
Yurui Zhang ◽  
Ned Buijs ◽  
Vito Thijssen ◽  
Davide Sartini ◽  
...  
Keyword(s):  
Cyclic Peptides ◽  
Cyclic Peptide ◽  
Peptide Inhibitors ◽  
Allosteric Inhibitors ◽  
Disease States ◽  
Potent Inhibition ◽  
Macrocyclic Peptides ◽  
Diabetes And Obesity ◽  
Substrate Competition

<p>Nicotinamide <i>N</i>-methyltransferase (NNMT) methylates nicotinamide to form 1-methylnicotinamide using <i>S</i>-adenosyl-l-methionine (SAM) as the methyl donor. The complexity of the role of NNMT in healthy and disease states is slowly being elucidated and provides indication that NNMT may be an interesting therapeutic target for a variety of diseases including cancer, diabetes, and obesity. Most inhibitors of NNMT described to date are structurally related to one or both of its substrates. In search of structurally diverse NNMT inhibitors, an mRNA display screening technique was used to identify macrocyclic peptides which bind to NNMT. Several of the cyclic peptides identified in this manner show potent inhibition of NNMT with IC<sub>50</sub> values as low as 229 nM. Interestingly, substrate competition experiments reveal that these cyclic peptide inhibitors are noncompetitive with either SAM or NA indicating they may be the first allosteric inhibitors reported for NNMT.</p>

Abstract 425: Protein Kinase Activity of Pi3kγ Regulates Insulin-βArs Cross-talk

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Anita SAHU ◽  
Sromona Mukherjee ◽  
Kate Stenson ◽  
Maradumane L Mohan ◽  
Sathyamangla V Prasad
Keyword(s):  
Hek293 Cells ◽  
Protein Kinase Activity ◽  
Pi3k Inhibitors ◽  
Pp2a Activity ◽  
Phosphatase 2A ◽  
Β Blocker ◽  
Sirna Knockdown ◽  
G Protein Coupled ◽  
Diabetes And Obesity

β adrenergic receptor (βAR) function is regulated by G-protein coupled receptor (GPCR) kinase (GRK) driven desensitization and protein phosphatase 2A (PP2A) mediated resensitization to its classical agonist. Surprisingly, Insulin modulates (βARs) function thus regulating cardiac function. Although insulin is known to modulate βAR function through GRKs, less is known about insulin mediated resensitization mechanisms. PI3Kγ is activated by GPCRs regulates resensitization by inhibiting PP2A activity. Therefore, we tested whether insulin could mediate βAR dysfunction through inhibition of resensitization. Co-immunoprecipitation in cardiac lysates and surface plasmon resonance (SPR) with purified proteins show that PI3Kγ interacts with GRK-2 resulting in recruitment of GRK2-PI3Kγ to the β2AR complex upon insulin. Furthermore, use of PI3K inhibitors significantly reduced Insulin-stimulated β2ARs phosphorylation in HEK293 cells. The role of PI3Kγ was further validated by the loss of insulin stimulated β 2 AR phosphorylation in PI3Kγ-knockout (KO) mouse embryonic fibroblasts (MEFs), shRNA and CRIPSR knockdown of PI3Kγ. Data shows that PI3Kγ inhibits PP2A activity at the βAR complex upon insulin while loss of PI3Kγ unravels this inhibition resulting in increased PP2A activity leading to β2AR dephosphorylation and resensitization. Mechanistically, PI3Kγ inhibits PP2A activity at the β2AR complex by phosphorylating an endogenous inhibitor of PP2A (I2PP2A). CRISPR knockout and siRNA knockdown of endogenous I2PP2A in HEK293 cells restored PP2A activity resulting in β2AR dephosphorylation despite PI3Kγ. Furthermore, β blocker (propranolol) pretreatment did not affect β2AR phosphorylation and there was no β-arrestin recruitment to the βAR complex with Insulin. Together these studies show that Insulin mediates β2AR desensitization through β-agonist and β-arrestin independent mechanisms wherein, PI3Kγ-mediated regulation of PP2A activity plays a pivotal role in cardiac βAR function in hyperinsulemic conditions like diabetes and obesity.

scholarly journals Increased Expression of Meteorin-Like Hormone in Type 2 Diabetes and Obesity and Its Association with Irisin

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1283 ◽  
Author(s):  
AlKhairi ◽  
Cherian ◽  
Abu-Farha ◽  
Madhoun ◽  
Nizam ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Plasma Levels ◽  
Positive Association ◽  
Diabetic Patients ◽  
Metabolic Dysregulation ◽  
Strong Positive Association ◽  
Metabolic Biomarkers ◽  
Diabetes And Obesity

Type 2 diabetes (T2D) is a growing pandemic associated with metabolic dysregulation and chronic inflammation. Meteorin-like hormone (METRNL) is an adipomyokine that is linked to T2D. Our objective was to evaluate the changes in METRNL levels in T2D and obesity and assess the association of METRNL levels with irisin. Overall, 228 Arab individuals were enrolled. Plasma levels of METRNL and irisin were assessed using immunoassay. Plasma levels of METRNL and irisin were significantly higher in T2D patients than in non-diabetic patients (p < 0.05). When the population was stratified based on obesity, METRNL and irisin levels were significantly higher in obese than in non-obese individuals (p < 0.05). We found a significant positive correlation between METRNL and irisin (r = 0.233 and p = 0.001). Additionally, METRNL and irisin showed significant correlation with various metabolic biomarkers associated with T2D and Obesity. Our data shows elevated METRNL plasma levels in individuals with T2D, further exacerbated with obesity. Additionally, a strong positive association was observed between METRNL and irisin. Further studies are necessary to examine the role of these proteins in T2D and obesity, against their ethnic background and to understand the mechanistic significance of their possible interplay.

scholarly journals The Protective Effect of Exercise in Neurodegenerative Diseases: The Potential Role of Extracellular Vesicles

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2182 ◽  
Author(s):  
Oliver K Fuller ◽  
Martin Whitham ◽  
Suresh Mathivanan ◽  
Mark A Febbraio
Keyword(s):  
Physical Activity ◽  
Extracellular Vesicles ◽  
Potential Role ◽  
The Body ◽  
Therapeutic Effects ◽  
Health And Wellbeing ◽  
Systemic Factors ◽  
Diabetes And Obesity

Physical activity has systemic effects on the body, affecting almost every organ. It is important not only for general health and wellbeing, but also in the prevention of diseases. The mechanisms behind the therapeutic effects of physical activity are not completely understood; however, studies indicate these benefits are not confined to simply managing energy balance and body weight. They also include systemic factors which are released into the circulation during exercise and which appear to underlie the myriad of benefits exercise can elicit. It was shown that along with a number of classical cytokines, active tissues also engage in inter-tissue communication via extracellular vesicles (EVs), specifically exosomes and other small EVs, which are able to deliver biomolecules to cells and alter their metabolism. Thus, EVs may play a role in the acute and systemic adaptations that take place during and after physical activity, and may be therapeutically useful in the treatment of a range of diseases, including metabolic disorders such as type 2 diabetes and obesity; and the focus of this review, neurological disorders such as Alzheimer’s disease.

scholarly journals Role of Environmental Chemicals in Diabetes and Obesity: A National Toxicology Program Workshop Review

2012 ◽  
Vol 120 (6) ◽  
pp. 779-789 ◽  
Author(s):  
Kristina A. Thayer ◽  
Jerrold J. Heindel ◽  
John R. Bucher ◽  
Michael A. Gallo
Keyword(s):  
Environmental Chemicals ◽  
National Toxicology Program ◽  
Diabetes And Obesity

scholarly journals Insights into the role of neuronal glucokinase

2016 ◽  
Vol 311 (1) ◽  
pp. E42-E55 ◽  
Author(s):  
Ivan De Backer ◽  
Sufyan S. Hussain ◽  
Stephen R. Bloom ◽  
James V. Gardiner
Keyword(s):  
Glucose Homeostasis ◽  
Brain Regions ◽  
Glucose Sensing ◽  
Clinical Implications ◽  
Sensing Mechanism ◽  
Novel Treatments ◽  
Diabetes And Obesity

Glucokinase is a key component of the neuronal glucose-sensing mechanism and is expressed in brain regions that control a range of homeostatic processes. In this review, we detail recently identified roles for neuronal glucokinase in glucose homeostasis and counterregulatory responses to hypoglycemia and in regulating appetite. We describe clinical implications from these advances in our knowledge, especially for developing novel treatments for diabetes and obesity. Further research required to extend our knowledge and help our efforts to tackle the diabetes and obesity epidemics is suggested.

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