scholarly journals Experimental and Emerging Free Fatty Acid Receptor Agonists for the Treatment of Type 2 Diabetes

Medicina ◽  
2022 ◽  
Vol 58 (1) ◽  
pp. 109
Author(s):  
Angelo Maria Patti ◽  
Rosaria Vincenza Giglio ◽  
Nikolaos Papanas ◽  
Dragos Serban ◽  
Anca Pantea Stoian ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Body Mass ◽  
Plasma Lipids ◽  
Metabolic Effects ◽  
Receptor Agonists ◽  
Electronic Database Search ◽  
Inflammatory Processes

The current management of Type 2 Diabetes Mellitus (T2DM) includes incretin-based treatments able to enhance insulin secretion and peripheral insulin sensitivity as well as improve body mass, inflammation, plasma lipids, blood pressure, and cardiovascular outcomes. Dietary Free Fatty Acids (FFA) regulate metabolic and anti-inflammatory processes through their action on incretins. Selective synthetic ligands for FFA1-4 receptors have been developed as potential treatments for T2DM. To comprehensively review the available evidence for the potential role of FFA receptor agonists in the treatment of T2DM, we performed an electronic database search assessing the association between FFAs, T2DM, inflammation, and incretins. Evidence indicates that FFA1-4 agonism increases insulin sensitivity, induces body mass loss, reduces inflammation, and has beneficial metabolic effects. There is a strong inter-relationship between FFAs and incretins. FFA receptor agonism represents a potential target for the treatment of T2DM and may provide an avenue for the management of cardiometabolic risk in susceptible individuals. Further research promises to shed more light on this emerging topic.

scholarly journals Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Denise E. Lackey ◽  
Felipe C. G. Reis ◽  
Roi Isaac ◽  
Rizaldy C. Zapata ◽  
Dalila El Ouarrat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Target Genes ◽  
Obese Mice ◽  
Tissue Macrophage

Abstract Insulin resistance is a key feature of obesity and type 2 diabetes. PU.1 is a master transcription factor predominantly expressed in macrophages but after HFD feeding PU.1 expression is also significantly increased in adipocytes. We generated adipocyte specific PU.1 knockout mice using adiponectin cre to investigate the role of PU.1 in adipocyte biology, insulin and glucose homeostasis. In HFD-fed obese mice systemic glucose tolerance and insulin sensitivity were improved in PU.1 AKO mice and clamp studies indicated improvements in both adipose and liver insulin sensitivity. At the level of adipose tissue, macrophage infiltration and inflammation was decreased and glucose uptake was increased in PU.1 AKO mice compared with controls. While PU.1 deletion in adipocytes did not affect the gene expression of PPARg itself, we observed increased expression of PPARg target genes in eWAT from HFD fed PU.1 AKO mice compared with controls. Furthermore, we observed decreased phosphorylation at serine 273 in PU.1 AKO mice compared with fl/fl controls, indicating that PPARg is more active when PU.1 expression is reduced in adipocytes. Therefore, in obesity the increased expression of PU.1 in adipocytes modifies the adipocyte PPARg cistrome resulting in impaired glucose tolerance and insulin sensitivity.

Glucose and Insulin Metabolism in Twins: Influence of Zygosity and Birth Weight

Twin Research ◽  
2001 ◽  
Vol 4 (5) ◽  
pp. 350-355 ◽  
Author(s):  
Pernille Poulsen ◽  
Allan Vaag
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Intolerance ◽  
Twin Studies ◽  
Metabolic Effects ◽  
Diabetes Research ◽  
Relative Role ◽  
Intrauterine Environment ◽  
Dizygotic Twins

AbstractSeveral epidemiological and metabolic studies have demonstrated an impact of the intrauterine environment on the development of disease in adult life, including Type 2 diabetes and glucose intolerance. Our finding of lower birth weights among monozygotic diabetic twins compared to their non-diabetic genetically identical co-twins confirms this association and, furthermore, eliminates the possibility that the association could be explained solely by common genes leading to both impaired intrauterine growth and increased risk of Type 2 diabetes. Due to an often shared placenta monozygotic twins may experience a more adverse intrauterine environment compared to dizygotic twins and may therefore be more prone to develop various metabolic abnormalities. Our findings of a higher glucose and insulin profile after oral glucose ingestion, and recently lower insulin-stimulated glucose uptake — indicating glucose intolerance and insulin resistance — among monozygotic compared to dizygotic twins may to some extent question the validity of classical twin studies in diabetes research where equal environmental influences in monozygotic and dizygotic twins is assumed. The potential role of an adverse intrauterine environment in causing Type 2 diabetes in humans, may to some degree alter our conception of the twin model in diabetes research including the interpretation of aetiological conclusions reached in previous classical twin studies of diabetes. However, our present knowledge is far too insufficient to discard the results from classical twin studies concerning the relative role of genes versus environment for the development of diabetes and its metabolic effects.

scholarly journals Effects of the SGLT2 Inhibitor Dapagliflozin on Energy Metabolism in Patients With Type 2 Diabetes: A Randomized, Double-Blind Crossover Trial

2021 ◽  
Author(s):  
Yvo J.M. Op den Kamp ◽  
Marlies de Ligt ◽  
Bas Dautzenberg ◽  
Esther Kornips ◽  
Russell Esterline ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Energy Metabolism ◽  
Caloric Restriction ◽  
Sglt2 Inhibitor ◽  
Metabolic Effects ◽  
Night Time ◽  
Double Blind ◽  
Urinary Glucose

<b>Background:</b> SGTL2 inhibitors increase urinary glucose excretion and have beneficial effects on cardiovascular and renal outcomes; the underlying mechanism may involve caloric restriction-like metabolic effects due to urinary glucose loss. We investigated the effects of dapagliflozin on 24h energy metabolism and insulin sensitivity in patients with type 2 diabetes mellitus. <p><b>Methods</b>: Twenty-six type 2 diabetes patients were randomized to a 5-week double-blind, cross-over study with 6-8-week wash-out. 24h energy metabolism and respiratory exchange ratio (RER) were measured by indirect calorimetry, both by whole-room calorimetry and by ventilated hood during a two-step euglycemic hyperinsulinemic clamp. Results are presented as the differences in least squares mean (LSM) (95% CI) between treatments.</p> <p><b>Results</b>: Evaluable patients (n=24) had a mean (SD) age of 64<b>.</b>2(4<b>.</b>6) years, BMI of 28<b>.</b>1(2<b>.</b>4) kg/m2, and HbA1c of 6.9 (0.7)% (51<b>.</b>7 (6<b>.</b>8) mmol/mol). Rate of glucose disappearance was unaffected by dapagliflozin, while fasting endogenous glucose production (EGP) increased by dapagliflozin (+2<b>.</b>27 (1<b>.</b>39, 3<b>.</b>14) μmol/kg/min, p<0<b>.</b>0001). Insulin-induced suppression of EGP (-1<b>.</b>71 (-2<b>.</b>75, -0<b>.</b>63) μmol/kg/min, p=0<b>.</b>0036) and plasma free fatty acids (-21<b>.</b>93 (-39<b>.</b>31, -4<b>.</b>54) %, p=0.016) was greater with dapagliflozin. 24h energy expenditure (-0.11 (-0.24, 0.03) MJ/day) remained unaffected by dapagliflozin, but dapagliflozin reduced RER during day- and night-time resulting in an increased day to night-time difference in RER (-0.010 (-0.017, -0.002), p=0.016). Dapagliflozin treatment resulted in a negative 24h energy and fat balance (-20.51 (-27.90, -13.12) g/day). </p> <p><b>Interpretation</b>: Dapagliflozin treatment for 5 weeks resulted in major adjustments of metabolism mimicking caloric restriction; increased fat oxidation, improved hepatic and adipose insulin sensitivity and improved 24h energy metabolism.</p>

scholarly journals Metabolic Effects of Testosterone Replacement Therapy in Patients with Type 2 Diabetes Mellitus or Metabolic Syndrome: A Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Shu-ying Li ◽  
Ya-ling Zhao ◽  
Yu-fan Yang ◽  
Xi Wang ◽  
Min Nie ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Type 2 Diabetes Mellitus ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
Meta Analysis ◽  
Metabolic Effects ◽  
Testosterone Replacement Therapy

Background. Testosterone replacement therapy (TRT) is commonly used for the treatment of hypogonadism in men, which is often associated with type 2 diabetes mellitus (T2DM) and metabolic syndrome (Mets). Recent compiling evidence shows that TRT has beneficial metabolic effects on these patients. Objective. A meta-analysis has been conducted to evaluate the effects of TRT on cardiovascular metabolic factors. Methods. We conducted a systemic search on PubMed, Embase, Cochrane Library, Wanfang, and CNKI and selected randomized controlled trials (RCTs) to include. The efficacy of TRT on glycemia, insulin sensitivity, lipid profile, and body weight was meta-analyzed by Review Manager. Results. A total of 18 RCTs, containing 1415 patients (767 in TRT and 648 in control), were enrolled for the meta-analysis. The results showed that TRT could reduce HbA1c (MD = −0.67, 95% CI −1.35, −0.19, and P = 0.006 ) and improve HOMA-IR (homeostatic model assessment of insulin resistance) (SMD = −1.94, 95% CI −2.65, −1.23, and P < 0.0001 ). TRT could also decrease low-density lipoprotein (SMD = −0.50, 95% CI −0.82, −0.90, and P = 0.002 ) and triglycerides (MD = −0.64, 95% CI −0.91, −0.36, and P < 0.0001 ). In addition, TRT could reduce body weight by 3.91 kg (MD = −3.91, 95% CI −4.14, −3.69, and P < 0.00001 ) and waist circumference by 2.8 cm (MD −2.80, 95% CI −4.38, −1.21 and P = 0.0005 ). Erectile dysfunction (measured by IIEF-5) did not improve, while aging-related symptoms (measured by AMS scores) significantly improved. Conclusions. TRT improves glycemic control, insulin sensitivity, and lipid parameters in hypogonadism patients with T2DM and MetS, partially through reducing central obesity.

scholarly journals The Role of Diet on Insulin Sensitivity

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3042
Author(s):  
Maria Mirabelli ◽  
Diego Russo ◽  
Antonio Brunetti
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Insulin Sensitivity ◽  
Dietary Composition ◽  
Reproductive Disorders

Growing evidence shows that dietary composition has a marked impact on the risk of developing obesity, type 2 diabetes (T2D), cardiovascular disease (CVD), certain types of endocrine cancer and many other intertwined metabolic and reproductive disorders, all featured by insulin resistance (IR) [...]

The role of GLP-1 receptor agonists as weight loss agents in patients with and without type 2 diabetes

2015 ◽  
Vol 32 (8) ◽  
pp. 297-300b ◽  
Author(s):  
Shujah Dar ◽  
Abd A Tahrani ◽  
Milan K Piya
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Receptor Agonists
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