scholarly journals Deletion of EHD2 Attenuated Adipocyte Hypertrophic Expansion and Ameliorated Diet-Induced Obesity and Insulin Resistance

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1633-1633
Author(s):  
Darius Fox ◽  
Ashley Toney ◽  
Mikyoung You ◽  
Hamid Band ◽  
Soonkyu Chung
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
Plasma Glucose ◽  
Insulin Signaling ◽  
Adipocyte Differentiation ◽  
Adipocyte Size ◽  
Lipogenic Gene ◽  
Insulin Levels ◽  
Gene And Protein Expression

Abstract Objectives Obesity induces adipocyte hypertrophy, which promotes metabolic dysfunction. The EPS15-Homology Domain-Containing (EHD) 2 is an endocytic traffic-regulatory protein regulating caveolae stability, thereby participating cell size expansion. Although EHD2 is abundantly expressed in adipocytes, very little information is available on its role on adipose metabolism. This study aimed to define the role of EHD2 on governing adipocyte size, lipid metabolism and insulin sensitivity. Methods To prepare the EHD2-deficient adipocytes, primary ear mesenchymal stem cells were isolate from wildtype (WT) and EHD2 KO mice and induced differentiation into adipocytes. To induce obesity and insulin resistance, EHD2 KO and WT male mice were fed a high-fat diet (50% calorie from lard) for 8 weeks. The changes in body weight was monitored weekly. Fasting plasma glucose and insulin levels were determined by glucometer and ELISA respectively. Glucose tolerance test (GTT) was conducted after HF diet feeding. To investigate insulin signaling, human recombinant insulin (1 U/kg BW) was injected peritoneally and epididymal fat was collected immediately for measuring the phosphorylation levels of AKT (p-AKT), a downstream target for insulin. To determine the lipogenic gene and protein expression, qPCR and Western blot analysis were conducted. Results Deletion of EHD2 markedly upregulated EHD1 expression in primary adipocytes. Also, deletion of EHD2 significantly attenuated adipocyte differentiation and maintained smaller lipid droplets. Consistently, absence of EHD2 was linked with reduced lipogenic gene expression. In vivo study, EHD2 KO mice exhibited slightly lower total body weight, but fat mass was markedly reduced. After 8 weeks of HF diet, EHD2 KO mice had lower levels of plasma glucose and insulin levels compared with WT. EHD2 KO mice were more glucose tolerant during GTT. Insulin signaling study revealed that EHD2 KO mice showed higher levels of insulin-stimulated p-AKT compared to WT mice, indicating EHD2 deletion promotes insulin sensitivity. Conclusions This study suggests that EHD2 is required for maximal adipocyte differentiation and hypertrophic expansion. The absence of EHD2 was linked with improved insulin and glucose sensitivity, presumably due to reduced adiposity and adipocyte size. Funding Sources Nebraska EPSCoR (Food for Health 2017) Seed Grant.

Abstract 3512: Disruption of Whole Nitric Oxide Synthase System Causes Impaired Glucose Tolerance and Insulin Resistance in Mice in Vivo

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Sei Nakata ◽  
Masato Tsutsui ◽  
Hiroaki Shimokawa ◽  
Ken Sabanai ◽  
Yasuko Yatera ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Pancreatic Islets ◽  
Plasma Glucose ◽  
Insulin Levels

Background : Nitric oxide (NO) synthase (NOS) system consists of 3 different isoforms, including neuronal (nNOS), inducible (iNOS), and endothelial NOSs (eNOS). We have recently succeeded in developing mice lacking all NOS genes (triply n/i/eNOS-KO mice) ( PNAS 2005). Our preliminary study has revealed that the triply-KO mice develop acute myocardial infarction (AMI). The present study was designed to investigate abnormalities of glucose metabolism, an important risk factor of MI, in those mice. Methods and Results : Experiments were performed in 3-month-old male wild-type (WT) and triply-KO mice (n=5–7). At 15 minutes after intravenous glucose administration (1 g/kg), plasma glucose levels (mg/dl) were significantly higher in the triply-KO (475 ± 44) than in the WT mice (241 ± 20) ( P< 0.05), and plasma insulin levels (ng/dl) were significantly lower in the triply-KO (0.50 ± 0.03) than in the WT mice (0.78 ± 0.03) ( P< 0.05). In the triply-KO mice, the size of pancreatic islets (islet/pancreatic area, 0.64 ± 0.16 vs. 2.81 ± 0.64%) was significantly smaller ( P< 0.05), and significant apoptosis of pancreatic islets (apoptotic/total islets, 19 ± 2 vs. 3 ± 1%) (TUNEL staining) was noted as compared with the WT mice ( P< 0.05). Furthermore, insulin sensitivity (as assessed by insulin-induced [ 3 H]-glucose uptake in isolated soleus muscle) (fold increase) was markedly reduced in the triply-KO mice (1.1 ± 0.03) as compared with the WT mice (2.1 ± 0.3) ( P< 0.05), associated with an impairment of insulin-induced translocation of glucose transporter-4 (GLUT-4) to the cellular membrane (immunofluorescent staining) ( P< 0.05). Importantly, supplementation of NO by long-term treatment with isosorbide dinitrate (0.4 mg/day, 6 weeks, dermal application) significantly reversed all these abnormalities of glucose metabolism in the triply-KO mice; plasma glucose (280 ± 28) and insulin levels (0.89 ± 0.10) after glucose tolerance test, insulin sensitivity (1.5 ± 0.08), and GLUT-4 translocation were all improved (all P< 0.05). Conclusions : These results indicate that disruption of whole NOSs system causes impaired glucose tolerance and insulin resistance in mice in vivo, suggesting a critical role of endogenous NO/NOSs system in maintaining glucose metabolism.

scholarly journals Angiotensin II type 2 receptor promotes adipocyte differentiation and restores adipocyte size in high-fat/high-fructose diet-induced insulin resistance in rats

2013 ◽  
Vol 304 (2) ◽  
pp. E197-E210 ◽  
Author(s):  
Michaël Shum ◽  
Sandra Pinard ◽  
Marie-Odile Guimond ◽  
Sébastien M. Labbé ◽  
Claude Roberge ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Angiotensin Ii ◽  
Lipid Droplets ◽  
Adipocyte Differentiation ◽  
Ang Ii ◽  
Adipocyte Size ◽  
High Fat ◽  
High Fructose

This study was aimed at establishing whether specific activation of angiotensin II (ANG II) type 2 receptor (AT2R) modulates adipocyte differentiation and function. In primary cultures of subcutaneous (SC) and retroperitoneal (RET) preadipocytes, both AT2R and AT1R were expressed at the mRNA and protein level. Cells were stimulated with ANG II or the AT2R agonist C21/M24, alone or in the presence of the AT1R antagonist losartan or the AT2R antagonist PD123,319. During differentiation, C21/M24 increased PPARγ expression in both RET and SC preadipocytes while the number of small lipid droplets and lipid accumulation solely increased in SC preadipocytes. In mature adipocytes, C21/M24 decreased the mean size of large lipid droplets. Upon abolishment of AT2R expression using AT2R-targeted shRNAs, expressions of AT2R, aP2, and PPARγ remained very low, and cells were unable to differentiate. In Wistar rats fed a 6-wk high-fat/high-fructose (HFHF) diet, a significant shift toward larger adipocytes was observed in RET and SC adipose tissue depots. C21/M24 treatments for 6 wk restored normal adipocyte size distribution in both these tissue depots. Moreover, C21/M24 and losartan decreased hyperinsulinemia and improved insulin sensitivity impaired by HFHF diet. A strong correlation between adipocyte size area and glucose infusion rate during euglycemic-hyperinsulinemic clamp was observed. These results indicate that AT2R is involved in early adipocyte differentiation, while in mature adipocytes and in a model of insulin resistance AT2R activation restores normal adipocyte morphology and improves insulin sensitivity.

scholarly journals The Impact of Differentiation on Cytotoxicity and Insulin Sensitivity in Streptozotocin Treated SH-SY5Y Cells

2021 ◽  
Vol 46 (6) ◽  
pp. 1350-1358
Author(s):  
Fruzsina Bagaméry ◽  
Kamilla Varga ◽  
Kitti Kecsmár ◽  
István Vincze ◽  
Éva Szökő ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Insulin Signaling ◽  
Glycogen Synthase ◽  
Insulin Metabolism ◽  
Relative Significance ◽  
Differentiated Cells ◽  
Mature Neuron ◽  
The Right ◽  
The Impact

AbstractRecently neuronal insulin resistance was suggested playing a role in Alzheimer’s disease. Streptozotocin (STZ) is commonly used to induce impairment in insulin metabolism. In our previous work on undifferentiated SH-SY5Y cells the compound exerted cytotoxicity without altering insulin sensitivity. Nevertheless, differentiation of the cells to a more mature neuron-like phenotype may considerably affect the significance of insulin signaling and its sensitivity to STZ. We aimed at studying the influence of STZ treatment on insulin signaling in SH-SY5Y cells differentiated by retinoic acid (RA). Cytotoxicity of STZ or low serum (LS) condition and protective effect of insulin were compared in RA differentiated SH-SY5Y cells. The effect of insulin and an incretin analogue, exendin-4 on insulin signaling was also examined by assessing glycogen synthase kinase-3 (GSK-3) phosphorylation. STZ was found less cytotoxic in the differentiated cells compared to our previous results in undifferentiated SH-SY5Y cells. The cytoprotective concentration of insulin was similar in the STZ and LS groups. However, the right-shifted concentration–response curve of insulin induced GSK-3 phosphorylation in STZ-treated differentiated cells is suggestive of the development of insulin resistance that was further confirmed by the insulin potentiating effect of exendin-4. Differentiation reduced the sensitivity of SH-SY5Y cells for the non-specific cytotoxicity of STZ and enhanced the relative significance of development of insulin resistance. The differentiated cells thus serve as a better model for studying the role of insulin signaling in neuronal survival. However, direct cytotoxicity of STZ also contributes to the cell death.

scholarly journals Hyperandrogenism and Insulin Resistance, Not Changes in Body Weight, Mediate the Development of Endothelial Dysfunction in a Female Rat Model of Polycystic Ovary Syndrome (PCOS)

Endocrinology ◽  
2015 ◽  
Vol 156 (11) ◽  
pp. 4071-4080 ◽  
Author(s):  
Amanda Hurliman ◽  
Jennifer Keller Brown ◽  
Nicole Maille ◽  
Maurizio Mandala ◽  
Peter Casson ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Endothelial Dysfunction ◽  
Polycystic Ovary Syndrome ◽  
Rat Model ◽  
Polycystic Ovary ◽  
Phase 1 ◽  
Ovary Syndrome

This study was designed to differentiate the contributions of hyperandrogenism, insulin resistance (IR), and body weight to the development of endothelial dysfunction in polycystic ovary syndrome and determine the effectiveness of insulin sensitization and antiandrogenic therapy after the establishment of vascular and metabolic dysfunction using a rat model of polycystic ovary syndrome. We hypothesized that the observed endothelial dysfunction was a direct steroidal effect, as opposed to changes in insulin sensitivity or body weight. Prepubertal female rats were randomized to the implantation of a pellet containing DHT or sham procedure. In phase 1, DHT-exposed animals were randomized to pair feeding to prevent weight gain or metformin, an insulin-sensitizing agent, from 5 to 14 weeks. In phase 2, DHT-exposed animals were randomized to treatment with metformin or flutamide, a nonsteroidal androgen receptor blocker from 12 to 16 weeks. Endothelial function was assessed by the vasodilatory response of preconstricted arteries to acetylcholine. Serum steroid levels were analyzed in phase 1 animals. Fasting blood glucose and plasma insulin were analyzed and homeostasis model assessment index calculated in all animals. Our data confirm the presence of endothelial dysfunction as well as increased body weight, hypertension, hyperinsulinemia, and greater IR among DHT-treated animals. Even when normal weight was maintained through pair feeding, endothelial dysfunction, hyperinsulinemia, and IR still developed. Furthermore, despite weight gain, treatment with metformin and flutamide improved insulin sensitivity and blood pressure and restored normal endothelial function. Therefore, the observed endothelial dysfunction is most likely a direct result of hyperandrogenism-induced reductions in insulin sensitivity, as opposed to weight gain.

scholarly journals EFFECT OF ALOE BARBADENSIS MILLER WHOLE LEAF EXTRACT ON HYPERGLYCEMIA AND INSULIN RESISTANCE IN LOW DOSE STREPTOZOTOCIN INDUCED TYPE 2 DIABETIC RATS

1969 ◽  
Vol 3 (2) ◽  
pp. 350-355
Author(s):  
MEENA GUL ◽  
MUHAMMAD MAZHAR HUSSAIN ◽  
AYESHA BABER ◽  
AMJAD ZAMAN ◽  
MUSRAT ZAHRA
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Plasma Glucose ◽  
Leaf Extract ◽  
Low Dose ◽  
Aloe Vera ◽  
Control Group ◽  
Sprague Dawley ◽  
Type 2 Diabetic

BACKGROUND: Managing diabetes is difficult due to the number of side effects associated with drugsused for its treatment. There it is a need of an hour to look for indigenous plants which are safe and costeffective. Present study was planned to determine the effect of Aloe vera whole leaf extract and/orRosiglitazone on plasma glucose, insulin and insulin resistance in type 2 diabetic Sprague-Dawley rats.DESIGN: Randomized control trailPLACE AND DURATION OF STUDY: This study was conducted from April 2009 to Oct 2010 at theDepartment of Physiology Army Medical College, Rawalpindi in collaboration with National Institute ofHealth (NIH) Islamabad.MATERIAL AND METHOD: Type 2 DM was induced in 60 healthy Sprague-Dawley rats by feedinghigh fat diet for 2 weeks and injecting a low dose (35mg/kg) of streptozotocin intra peritoneally. Type 2diabetic rats were randomly divided into four groups, each group having 15 rats and were labeled as diabeticgroup, Aloe vera group, rosiglitazone group and combined group. The diabetic group was injected normalsaline, Aloe vera group was treated with Aloe vera whole leaf extract in dose of 300mg/kg body weight,rosiglitazone group was given 5mg/kg body weight of rosiglitazone I/P and combined group diabetic ratswere treated with 150mg/kg body weight of Aloevera extract and 2.5mg/kg body weight of rosiglitazone(halfof their effective dose) for 21 days.RESULTS: A significant reduction (p<0.001) in plasma glucose (73%), insulin (32%) and TG/HDL ratio(81%) was analyzed in combined groupascompared to diabetic control group. \CONCLUSION: The maximum impact in lowering plasma glucose, insulin and TG/HDL ratio wasrecorded in combined group, followed by rosiglitazone group and then Aloevera group.KEYWORDS:T2DM. Aloe vera, insulin resistance

Abstract P048: A Model Of Chronic Insufficient Sleep Increases Markers Of Insulin Resistance In Postmenopausal But Not Premenopausal Women

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Faris M Zuraikat ◽  
Samantha Scaccia ◽  
Ayanna Campbell ◽  
Bin Cheng ◽  
Marie-Pierre St-Onge
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Adverse Effects ◽  
Postmenopausal Women ◽  
Menopausal Status ◽  
Premenopausal Women ◽  
Full Sample ◽  
Insulin Levels ◽  
Short Sleep ◽  
Sleep Condition

Introduction: Insufficient sleep is widely prevalent among US adults and is a risk factor for type 2 diabetes (T2D). Experimental studies show adverse effects of acute, severe short sleep on insulin sensitivity, but it is unclear whether these reflect risks associated with milder short sleep routinely observed in the general population. To date, no study has evaluated the impact of prolonged mild sleep curtailment on markers of insulin resistance in women or whether these effects differ by menopausal status, known to impact insulin sensitivity. Hypothesis: Glucose and insulin levels, as well as a measure of insulin resistance (HOMA-IR), will increase during 6 wk of sleep restriction (SR) relative to adequate sleep (AS). Adverse effects of prolonged short sleep will be exacerbated in postmenopausal women. Methods: Thirty-four women (age: 38±14 y; BMI: 25.6±3.6 kg/m2; n=10 postmenopausal) with adequate habitual total sleep time (TST) (453±33 min) took part in a randomized crossover study with two 6-wk phases: AS and SR. In AS, participants were asked to maintain stable nightly bed and wake times determined from 2 wk of screening with wrist actigraphy and sleep logs. In SR, bedtime was delayed to reduce TST by approximately 1.5 h/night. Sleep was measured continuously using actigraphy and verified weekly for compliance. At wk 0, 3, 4, and 6 fasting blood samples were collected. Outcomes included glucose and insulin levels as well as HOMA-IR scores, calculated from those values. Linear-mixed models tested interactions of sleep condition with week on outcome measures in the full sample and by menopausal status. Results: Sleep condition impacted the change in TST from baseline (P<0.0001), which was reduced in SR and unchanged in AS (-79±6 vs -4±6min). In the full sample, there was no sleep condition by week interactions for glucose (P=0.67), insulin (P=0.14), or HOMA-IR (P=0.16). Similar results were observed in premenopausal women (all P>0.50). However, in postmenopausal women, there was a significant effect of sleep condition on change in insulin (P=0.046) and HOMA-IR (P=0.039) over the 6 wk. In SR, insulin (slope: 0.26±0.28 μU/mL) and HOMA-IR (slope: 0.07±0.08) increased, while AS resulted in reductions in these outcomes (insulin slope: -0.56±0.29 μU/mL; HOMA-IR slope: -0.16±0.08). Conclusions: We provide the first evidence that chronic short sleep, even if mild, adversely affects insulin sensitivity in postmenopausal women. In contrast, maintenance of AS may improve glycemic regulation. Interestingly, prolonged short sleep did not impact markers of insulin resistance in premenopausal women; further investigation into these life-stage related differences, including underlying mechanisms, is warranted. Results suggest that, in postmenopausal women, a group at heightened risk of poor sleep and T2D, achieving adequate sleep may be an effective strategy to improve cardiometabolic health.

scholarly journals PGRN Induces Impaired Insulin Sensitivity and Defective Autophagy in Hepatic Insulin Resistance

2015 ◽  
Vol 29 (4) ◽  
pp. 528-541 ◽  
Author(s):  
Jiali Liu ◽  
Huixia Li ◽  
Bo Zhou ◽  
Lin Xu ◽  
Xiaomin Kang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Insulin Signaling ◽  
Nuclear Factor Κb ◽  
Hepatic Insulin Resistance ◽  
Causative Role ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Impaired Insulin

Abstract Progranulin (PGRN) has recently emerged as an important regulator for glucose metabolism and insulin sensitivity. However, the underlying mechanisms of PGRN in the regulation of insulin sensitivity and autophagy remain elusive. In this study, we aimed to address the direct effects of PGRN in vivo and to evaluate the potential interaction of impaired insulin sensitivity and autophagic disorders in hepatic insulin resistance. We found that mice treated with PGRN for 21 days exhibited the impaired glucose tolerance and insulin tolerance and hepatic autophagy imbalance as well as defective insulin signaling. Furthermore, treatment of mice with TNF receptor (TNFR)-1 blocking peptide-Fc, a TNFR1 blocking peptide-Fc fusion protein to competitively block the interaction of PGRN and TNFR1, resulted in the restoration of systemic insulin sensitivity and the recovery of autophagy and insulin signaling in liver. Consistent with these findings in vivo, we also observed that PGRN treatment induced defective autophagy and impaired insulin signaling in hepatocytes, with such effects being drastically nullified by the addition of TNFR1 blocking peptide -Fc or TNFR1-small interference RNA via the TNFR1-nuclear factor-κB-dependent manner, indicating the causative role of PGRN in hepatic insulin resistance. In conclusion, our findings supported the notion that PGRN is a key regulator of hepatic insulin resistance and that PGRN may mediate its effects, at least in part, by inducing defective autophagy via TNFR1/nuclear factor-κB.

scholarly journals Role of Cannabinoid Receptor Type 1 in Insulin Resistance and Its Biological Implications

2019 ◽  
Vol 20 (9) ◽  
pp. 2109 ◽  
Author(s):  
Arulkumar Nagappan ◽  
Jooyeon Shin ◽  
Myeong Ho Jung
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
Hepatic Steatosis ◽  
Cannabinoid Receptor ◽  
Inflammatory Responses ◽  
Hepatic Insulin Resistance ◽  
Leptin Resistance ◽  
Peripheral Tissues

Endogenous cannabinoids (ECs) are lipid-signaling molecules that specifically bind to cannabinoid receptor types 1 and 2 (CB1R and CB2R) and are highly expressed in central and many peripheral tissues under pathological conditions. Activation of hepatic CB1R is associated with obesity, insulin resistance, and impaired metabolic function, owing to increased energy intake and storage, impaired glucose and lipid metabolism, and enhanced oxidative stress and inflammatory responses. Additionally, blocking peripheral CB1R improves insulin sensitivity and glucose metabolism and also reduces hepatic steatosis and body weight in obese mice. Thus, targeting EC receptors, especially CB1R, may provide a potential therapeutic strategy against obesity and insulin resistance. There are many CB1R antagonists, including inverse agonists and natural compounds that target CB1R and can reduce body weight, adiposity, and hepatic steatosis, and those that improve insulin sensitivity and reverse leptin resistance. Recently, the use of CB1R antagonists was suspended due to adverse central effects, and this caused a major setback in the development of CB1R antagonists. Recent studies, however, have focused on development of antagonists lacking adverse effects. In this review, we detail the important role of CB1R in hepatic insulin resistance and the possible underlying mechanisms, and the therapeutic potential of CB1R targeting is also discussed.

scholarly journals Metabolic recovery of adipose tissue is associated with improvement in insulin resistance in a model of experimental diabetes

2008 ◽  
Vol 198 (1) ◽  
pp. 51-60 ◽  
Author(s):  
Julie Takada ◽  
Miriam Helena Fonseca-Alaniz ◽  
Tarcila Beatriz Ferraz de Campos ◽  
Sandra Andreotti ◽  
Amanda Baron Campana ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Energy Homeostasis ◽  
Hormone Secretion ◽  
Active Role ◽  
Metabolic Disturbances ◽  
Severe Insulin Resistance ◽  
Insulin Levels ◽  
Adipose Mass

Obesity and insulin resistance are highly correlated with metabolic disturbances. Both the excess and lack of adipose tissue can lead to severe insulin resistance and diabetes. Adipose tissue plays an active role in energy homeostasis, hormone secretion, and other proteins that affect insulin sensitivity, appetite, energy balance, and lipid metabolism. Rats with streptozotocin-induced diabetes during the neonatal period develop the classic diabetic picture of hyperglycemia, hypoinsulinemia, and insulin resistance in adulthood. Low body weight and reduced epididymal (EP) fat mass were also seen in this model. The aim of this study was to investigate the glucose homeostasis and metabolic repercussions on the adipose tissue following chronic treatment with antidiabetic drugs in these animals. In the 4th week post birth, diabetic animals started an 8-week treatment with pioglitazone, metformin, or insulin. Animals were then killed, EP fat pads were excised, and blood samples were collected for biological and biochemical assays. Pioglitazone and insulin treatments, but not metformin, reduced hyperglycemia, polydipsia, and polyphagia. Although all antidiabetic therapies improved insulin sensitivity, this was particularly noteworthy in the pioglitazone-treated rats. Furthermore, a recovery of adipose mass and insulin levels were observed in pioglitazone- and insulin-, but not metformin-treated animals. Treatments with insulin or pioglitazone were able to correct significantly, but not completely, the metabolic abnormalities, parallel to full recovery of adipose mass, indicating that not only the low insulin levels but also the lack of adipose tissue might play a significant role on the pathophysiology of this particular diabetes model.

scholarly journals Comprehensive functional screening of miRNAs involved in fat cell insulin sensitivity among women

2017 ◽  
Vol 312 (6) ◽  
pp. E482-E494 ◽  
Author(s):  
Ingrid Dahlman ◽  
Yasmina Belarbi ◽  
Jurga Laurencikiene ◽  
Annie M. Pettersson ◽  
Peter Arner ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Differential Expression ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Functional Screening ◽  
Fat Cell ◽  
Subcutaneous White Adipose Tissue ◽  
Micro Rnas

The key pathological link between obesity and type 2 diabetes is insulin resistance, but the molecular mechanisms are not entirely identified. micro-RNAs (miRNA) are dysregulated in obesity and may contribute to insulin resistance. Our objective was to detect and functionally investigate miRNAs linked to insulin sensitivity in human subcutaneous white adipose tissue (scWAT). Subjects were selected based on the insulin-stimulated lipogenesis response of subcutaneous adipocytes. Global miRNA profiling was performed in abdominal scWAT of 18 obese insulin-resistance (OIR), 21 obese insulin-sensitive (OIS), and 9 lean women. miRNAs demonstrating differential expression between OIR and OIS women were overexpressed in human in vitro-differentiated adipocytes followed by assessment of lipogenesis and identification of miRNA targets by measuring mRNA/protein expression and 3′-untranslated region analysis. Eleven miRNAs displayed differential expression between OIR and OIS states. Overexpression of miR-143-3p and miR-652-3p increased insulin-stimulated lipogenesis in human in vitro differentiated adipocytes and directly or indirectly affected several genes/proteins involved in insulin signaling at transcriptional or posttranscriptional levels. Adipose expression of miR-143-3p and miR-652-3p was positively associated with insulin-stimulated lipogenesis in scWAT independent of body mass index. In conclusion, miR-143-3p and miR-652-3p are linked to scWAT insulin resistance independent of obesity and influence insulin-stimulated lipogenesis by interacting at different steps with insulin-signaling pathways.

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