Combination therapy with PPARγ and PPARα agonists increases glucose-stimulated insulin secretion in db/dbmice

2003 ◽  
Vol 284 (5) ◽  
pp. E966-E971 ◽  
Author(s):  
Ken Yajima ◽  
Hiroshi Hirose ◽  
Haruhisa Fujita ◽  
Yoshiko Seto ◽  
Hiroshi Fujita ◽  
...  
Keyword(s):  
Body Weight ◽  
Insulin Secretion ◽  
Weight Gain ◽  
Combination Therapy ◽  
Body Weight Gain ◽  
Nonesterified Fatty Acid ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Agonist ◽  
Glucose Stimulated Insulin Secretion

Although peroxisome proliferator-activated receptor (PPAR)γ agonists ameliorate insulin resistance, they sometimes cause body weight gain, and the effect of PPAR agonists on insulin secretion is unclear. We evaluated the effects of combination therapy with a PPARγ agonist, pioglitazone, and a PPARα agonist, bezafibrate, and a dual agonist, KRP-297, for 4 wk in male C57BL/6J mice and db/db mice, and we investigated glucose-stimulated insulin secretion (GSIS) by in situ pancreatic perfusion. Body weight gain in db/db mice was less with KRP-297 treatment than with pioglitazone or pioglitazone + bezafibrate treatment. Plasma glucose, insulin, triglyceride, and nonesterified fatty acid levels were elevated in untreated db/db mice compared with untreated C57BL/6J mice, and these parameters were significantly ameliorated in the PPARγ agonist-treated groups. Also, PPARγ agonists ameliorated the diminished GSIS and insulin content, and they preserved insulin and GLUT2 staining in db/db mice. GSIS was further increased by PPARγ and -α agonists. We conclude that combination therapy with PPARγ and PPARα agonists may be more useful with respect to body weight and pancreatic GSIS in type 2 diabetes with obesity.

scholarly journals Deficiency of FcϵR1 Increases Body Weight Gain but Improves Glucose Tolerance in Diet-Induced Obese Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (11) ◽  
pp. 4047-4058 ◽  
Author(s):  
Yun-Jung Lee ◽  
Conglin Liu ◽  
Mengyang Liao ◽  
Galina K. Sukhova ◽  
Jun Shirakawa ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Insulin Secretion ◽  
Weight Gain ◽  
Glucose Tolerance ◽  
Glucose Uptake ◽  
Body Weight Gain ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Enhancer Binding Protein

Prior studies demonstrated increased plasma IgE in diabetic patients, but the direct participation of IgE in diabetes or obesity remains unknown. This study found that plasma IgE levels correlated inversely with body weight, body mass index, and body fat mass among a population of randomly selected obese women. IgE receptor FcϵR1-deficient (Fcer1a−/−) mice and diet-induced obesity (DIO) mice demonstrated that FcϵR1 deficiency in DIO mice increased food intake, reduced energy expenditure, and increased body weight gain but improved glucose tolerance and glucose-induced insulin secretion. White adipose tissue from Fcer1a−/− mice showed an increased expression of phospho-AKT, CCAAT/enhancer binding protein-α, peroxisome proliferator-activated receptor-γ, glucose transporter-4 (Glut4), and B-cell lymphoma 2 (Bcl2) but reduced uncoupling protein 1 (UCP1) and phosphorylated c-Jun N-terminal kinase (JNK) expression, tissue macrophage accumulation, and apoptosis, suggesting that IgE reduces adipogenesis and glucose uptake but induces energy expenditure, adipocyte apoptosis, and white adipose tissue inflammation. In 3T3-L1 cells, IgE inhibited the expression of CCAAT/enhancer binding protein-α and peroxisome proliferator-activated receptor-γ, and preadipocyte adipogenesis and induced adipocyte apoptosis. IgE reduced the 3T3-L1 cell expression of Glut4, phospho-AKT, and glucose uptake, which concurred with improved glucose tolerance in Fcer1a−/− mice. This study established two novel pathways of IgE in reducing body weight gain in DIO mice by suppressing adipogenesis and inducing adipocyte apoptosis while worsening glucose tolerance by reducing Glut4 expression, glucose uptake, and insulin secretion.

scholarly journals Peroxisome Proliferator-Activated Receptor α (PPARα) Potentiates, whereas PPARγ Attenuates, Glucose-Stimulated Insulin Secretion in Pancreatic β-Cells

Endocrinology ◽  
2005 ◽  
Vol 146 (8) ◽  
pp. 3266-3276 ◽  
Author(s):  
Kim Ravnskjaer ◽  
Michael Boergesen ◽  
Blanca Rubi ◽  
Jan K. Larsen ◽  
Tina Nielsen ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Mitochondrial Membrane ◽  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Stimulated Insulin Secretion

Abstract Fatty acids (FAs) are known to be important regulators of insulin secretion from pancreatic β-cells. FA-coenzyme A esters have been shown to directly stimulate the secretion process, whereas long-term exposure of β-cells to FAs compromises glucose-stimulated insulin secretion (GSIS) by mechanisms unknown to date. It has been speculated that some of these long-term effects are mediated by members of the peroxisome proliferator-activated receptor (PPAR) family via an induction of uncoupling protein-2 (UCP2). In this study we show that adenoviral coexpression of PPARα and retinoid X receptor α (RXRα) in INS-1E β-cells synergistically and in a dose- and ligand-dependent manner increases the expression of known PPARα target genes and enhances FA uptake and β-oxidation. In contrast, ectopic expression of PPARγ/RXRα increases FA uptake and deposition as triacylglycerides. Although the expression of PPARα/RXRα leads to the induction of UCP2 mRNA and protein, this is not accompanied by reduced hyperpolarization of the mitochondrial membrane, indicating that under these conditions, increased UCP2 expression is insufficient for dissipation of the mitochondrial proton gradient. Importantly, whereas expression of PPARγ/RXRα attenuates GSIS, the expression of PPARα/RXRα potentiates GSIS in rat islets and INS-1E cells without affecting the mitochondrial membrane potential. These results show a strong subtype specificity of the two PPAR subtypes α and γ on lipid partitioning and insulin secretion when systematically compared in a β-cell context.

scholarly journals Cyanidin-3-O-Galactoside-Enriched Aronia melanocarpa Extract Attenuates Weight Gain and Adipogenic Pathways in High-Fat Diet-Induced Obese C57BL/6 Mice

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1190 ◽  
Author(s):  
Su-Min Lim ◽  
Hyun Sook Lee ◽  
Jae In Jung ◽  
So Mi Kim ◽  
Nam Young Kim ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Binding Protein ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Aronia Melanocarpa

Aronia melanocarpa are a rich source of anthocyanins that have received considerable interest for their relations to human health. In this study, the anti-adipogenic effect of cyanidin-3-O-galactoside-enriched Aronia melanocarpa extract (AM-Ex) and its underlying mechanisms were investigated in an in vivo system. Five-week-old male C57BL/6N mice were randomly divided into five groups for 8-week feeding with a control diet (CD), a high-fat diet (HFD), or a HFD with 50 (AM-Ex 50), 100 (AM-Ex 100), or 200 AM-Ex (AM-Ex 200) mg/kg body weight/day. HFD-fed mice showed a significant increase in body weight compared to the CD group, and AM-Ex dose-dependently inhibited this weight gain. AM-Ex significantly reduced the food intake and the weight of white fat tissue, including epididymal fat, retroperitoneal fat, mesenteric fat, and inguinal fat. Treatment with AM-Ex (50 to 200 mg/kg) reduced serum levels of leptin, insulin, triglyceride, total cholesterol, and low density lipoprotein (LDL)-cholesterol. Real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that AM-Ex suppressed adipogenesis by decreasing CCAAT/enhancer binding protein α, peroxisome proliferator-activated receptor γ, sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptor gamma coactivator-1α, acetyl-CoA carboxylase 1, ATP-citrate lyase, fatty acid synthase, and adipocyte protein 2 messenger RNA (mRNA) expressions. These results suggest that AM-Ex is potentially beneficial for the suppression of HFD-induced obesity by modulating multiple pathways associated with adipogenesis and food intake.

Long-term high animal protein diet reduces body weight gain and insulin secretion in diet-induced obese rats

2012 ◽  
Vol 92 (13) ◽  
pp. 2638-2643 ◽  
Author(s):  
Haiyan Chen ◽  
Yiling Wang ◽  
Lichuan Ma ◽  
Jiajun Zhao ◽  
Yinyin Li ◽  
...  
Keyword(s):  
Body Weight ◽  
Insulin Secretion ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Animal Protein ◽  
Protein Diet ◽  
High Animal ◽  
Obese Rats

scholarly journals Methyl Caffeate Isolated from the Flowers of Prunus persica (L.) Batsch Enhances Glucose-Stimulated Insulin Secretion

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 279
Author(s):  
Dahae Lee ◽  
Yutong Qi ◽  
Ranhee Kim ◽  
Jungbin Song ◽  
Hocheol Kim ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Phenolic Compounds ◽  
Prunus Persica ◽  
Cell Function ◽  
Bioactive Compound ◽  
Peroxisome Proliferator ◽  
Western Blot Assay ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Stimulated Insulin Secretion ◽  
Methyl Caffeate

Phenolic compounds from natural products are considered effective enhancers of insulin secretion to prevent and treat type 2 diabetes (T2DM). The flowers of Prunus persica (L.) Batsch also contain many phenolic compounds. In this study, the extract of flowers of P. persica (PRPE) exhibited an insulin secretion effect in a glucose-stimulated insulin secretion (GSIS) assay, which led us to isolate and identify the bioactive compound(s) responsible for these effects. Compounds isolated from PRPE were screened for their efficacy in INS-1 rat pancreatic β-cells. Among them, caffeic acid (5), methyl caffeate (6), ferulic acid (7), chlorogenic acid (8), naringenin (11), nicotiflorin (12), and astragalin (13) isolated from PRPE increased GSIS without inducing cytotoxicity. Interestingly, the GSIS effect of methyl caffeate (6) as a phenolic compound was similar to gliclazide, an antidiabetic sulfonylurea drug. Western blot assay showed that methyl caffeate (6) enhanced the related signaling proteins of the activated pancreatic and duodenal homeobox-1 (PDX-1) and peroxisome proliferator-activated receptor-γ (PPAR-γ), but also the phosphorylation of the total insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), and Akt, which influence β-cell function and insulin secretion. This study provides evidence that methyl caffeate (6) isolated from PRPE may aid in the management of T2DM.

scholarly journals Nigella Sativa and Ginger Increase GLUT4 and PPARγ in Metabolic Syndrome‐Induced Rats

2021 ◽  
Vol 11 (1) ◽  
pp. 3261-3269
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Body Weight ◽  
Glucose Transporter ◽  
Nigella Sativa ◽  
Body Weight Gain ◽  
Male Rats ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Increased fructose intake has been linked to the epidemiology of insulin resistance, type 2 diabetes mellitus, renal damage, and metabolic syndrome (MS). As oxidative stress plays a pivotal role in the pathology of insulin resistance, the present study was conducted to investigate the effects of Nigella Sativa (NS) and ginger as potent antioxidants on fructose-induced MS in rats. Male rats were fed with a high‐fructose high-fat-fed diet for 8 weeks. By the end of the 8th week, rats were divided into four groups; one was left untreated (normal control) and MS control group was treated with saline. MS groups were given Nigella sativa (4 ml/kg) and ginger (500 mg/kg) daily for 4 weeks. Markers chosen for assessment included the effect on body weight gain, glucose, insulin, adiponectin levels, and lipid profile. Also, protein expressions were estimated by glucose transporter 4 (GLUT4) content and peroxisome proliferator‐activated receptor‐gamma (PPARγ). Nigella sativa and ginger ameliorated some manifestations of MS, including an increase in body weight, glucose, insulin level, and resistance. Besides, both drugs lowered insulin resistance, induced hyperlipidemia and increased adiponectin level. Drugs also increased GLUT4 and PPARγ protein expression compared with MS control group. Nigella sativa and ginger ameliorated parameters of MS via increased GLUT4 and PPARγ expression.

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