A combination of borage seed oil and quercetin reduces fat accumulation and improves insulin sensitivity in obese rats

2020 ◽  
Vol 11 (5) ◽  
pp. 4512-4524 ◽  
Author(s):  
Paula Aranaz ◽  
María Zabala ◽  
Ana Romo-Hualde ◽  
David Navarro-Herrera ◽  
Miguel López-Yoldi ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Seed Oil ◽  
Liver Steatosis ◽  
Key Factors ◽  
Fat Accumulation ◽  
Obese Rats

Borage seed oil (BSO) combined with quercetin improves glucose tolerance, insulin sensitivity, liver steatosis and adiposity in pre-obese rats. The combination also inhibits adipogenesis in vitro by affecting some adipogenesis-key factors.

Insulin sensitivity in adipocytes from subjects with varying degrees of glucose tolerance

1986 ◽  
Vol 251 (3) ◽  
pp. E306-E310
Author(s):  
J. E. Foley ◽  
P. Thuillez ◽  
S. Lillioja ◽  
J. Zawadzki ◽  
C. Bogardus
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Transport ◽  
Insulin Binding ◽  
Normal Glucose Tolerance ◽  
Dependent Diabetes Mellitus ◽  
Oral Glucose ◽  
Pima Indians ◽  
Wide Range

Previous studies showed that the sensitivity of glucose transport to insulin is lower in adipocytes isolated from subjects with noninsulin-dependent diabetes mellitus and impaired glucose tolerance compared with subjects with normal glucose tolerance. This study analyzed the relationship between insulin sensitivity of glucose transport and glycemia in a large group of nondiabetic-nonglucose-intolerant subjects with a wide range of glycemic response to oral glucose. Seventy-four Pima Indians with 2-h postglucose load glucoses between 77 and 197 mg/100 ml, fasting plasma glucoses between 76 and 108 mg/100 ml, and no postload glucoses less than 199 mg/100 ml were studied. Isolated adipocytes were prepared in vitro after an abdominal fat biopsy, ED50 of insulin for glucose transport was correlated with 2-h postload glucoses, but not between insulin binding per cell or per cell surface area or in ED50 of insulin for antilipolysis and 2-h postglucose load glucoses. Although only 17% of the variation in glucose tolerance could be explained by a change in the sensitivity of glucose transport to insulin, the data suggests that a postinsulin-binding defect in the coupling of insulin binding to glucose transport may be an early step in the development of insulin resistance in human adipocytes.

scholarly journals β-Hydroxybutyrate is reduced in humans with obesity-related NAFLD and displays a dose-dependent effect on skeletal muscle mitochondrial respiration in vitro

2020 ◽  
Vol 319 (1) ◽  
pp. E187-E195 ◽  
Author(s):  
Jacob T. Mey ◽  
Melissa L. Erickson ◽  
Christopher L. Axelrod ◽  
William T. King ◽  
Chris A. Flask ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Oxygen Consumption ◽  
Insulin Sensitivity ◽  
Mitochondrial Respiration ◽  
Liver Fat ◽  
Whole Body ◽  
Fat Accumulation ◽  
Impaired Insulin ◽  
Hepatic Fat

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic fat accumulation and impaired insulin sensitivity. Reduced hepatic ketogenesis may promote these pathologies, but data are inconclusive in humans and the link between NAFLD and reduced insulin sensitivity remains obscure. We investigated individuals with obesity-related NAFLD and hypothesized that β-hydroxybutyrate (βOHB; the predominant ketone species) would be reduced and related to hepatic fat accumulation and insulin sensitivity. Furthermore, we hypothesized that ketones would impact skeletal muscle mitochondrial respiration in vitro. Hepatic fat was assessed by 1H-MRS in 22 participants in a parallel design, case control study [Control: n = 7, age 50 ± 6 yr, body mass index (BMI) 30 ± 1 kg/m2; NAFLD: n = 15, age 57 ± 3 yr, BMI 35 ± 1 kg/m2]. Plasma assessments were conducted in the fasted state. Whole body insulin sensitivity was determined by the gold-standard hyperinsulinemic-euglycemic clamp. The effect of ketone dose (0.5–5.0 mM) on mitochondrial respiration was conducted in human skeletal muscle cell culture. Fasting βOHB, a surrogate measure of hepatic ketogenesis, was reduced in NAFLD (−15.6%, P < 0.01) and correlated negatively with liver fat ( r2 = 0.21, P = 0.03) and positively with insulin sensitivity ( r2 = 0.30, P = 0.01). Skeletal muscle mitochondrial oxygen consumption increased with low-dose ketones, attributable to increases in basal respiration (135%, P < 0.05) and ATP-linked oxygen consumption (136%, P < 0.05). NAFLD pathophysiology includes impaired hepatic ketogenesis, which is associated with hepatic fat accumulation and impaired insulin sensitivity. This reduced capacity to produce ketones may be a potential link between NAFLD and NAFLD-associated reductions in whole body insulin sensitivity, whereby ketone concentrations impact skeletal muscle mitochondrial respiration.

scholarly journals New insight into the mechanisms of ectopic fat deposition improvement after bariatric surgery

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Giulia Angelini ◽  
Lidia Castagneto Gissey ◽  
Giulia Del Corpo ◽  
Carla Giordano ◽  
Bruna Cerbelli ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Bariatric Surgery ◽  
Insulin Sensitivity ◽  
Hepatic Insulin Resistance ◽  
Alcoholic Fatty Liver ◽  
Fat Accumulation ◽  
Impaired Liver ◽  
Ectopic Fat Deposition

AbstractNon-alcoholic fatty-liver disease (NAFLD) is frequent in obese patients and represents a major risk factor for the development of diabetes and its complications. Bariatric surgery reverses the hepatic features of NAFLD. However, its mechanism of action remains elusive. We performed a comprehensive analysis of the mechanism leading to the improvement of NAFLD and insulin resistance in both obese rodents and humans following sleeve-gastrectomy (SG). SG improved insulin sensitivity and reduced hepatic and monocyte fat accumulation. Importantly, fat accumulation in monocytes was well comparable to that in hepatocytes, suggesting that Plin2 levels in monocytes might be a non-invasive marker for the diagnosis of NAFLD. Both in vitro and in vivo studies demonstrated an effective metabolic regeneration of liver function and insulin sensitivity. Specifically, SG improved NAFLD significantly by enhancing AMP-activated protein kinase (AMPK) phosphorylation and chaperone-mediated autophagy (CMA) that translate into the removal of Plin2 coating lipid droplets. This led to an increase in lipolysis and specific amelioration of hepatic insulin resistance. Elucidating the mechanism of impaired liver metabolism in obese subjects will help to design new strategies for the prevention and treatment of NAFLD.

scholarly journals Niacin improves adiponectin secretion, glucose tolerance and insulin sensitivity in diet-induced obese rats

2015 ◽  
Vol 2 (4) ◽  
pp. 261-267 ◽  
Author(s):  
Ayodele Olufemi Morakinyo ◽  
Titilola Aderonke Samuel ◽  
Daniel Abiodun Adekunbi ◽  
Olufeyi Adefunke Adegoke
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Obese Rats

scholarly journals 4-Hydroxyisoleucine Alleviates Macrophage-Related Chronic Inflammation and Metabolic Syndrome in Mice Fed a High-Fat Diet

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiali Yang ◽  
Yunhui Ran ◽  
Yonghui Yang ◽  
Shuyi Song ◽  
Yahong Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Chronic Inflammation ◽  
Immune Cells ◽  
High Fat Diet ◽  
Liver Steatosis ◽  
High Fat ◽  
Protein Amino Acid

In obesity, macrophages and other immune cells accumulate in organs affected by insulin, leading to chronic inflammation and insulin resistance. 4-Hydroxyisoleucine (4-HIL) is a non-protein amino acid found in fenugreek seeds. 4-HIL enhances insulin sensitivity, but its mechanism is still unclear. In this study, 4-HIL intervention reduced weight gain, liver steatosis, and dyslipidemia; moreover, it increased systemic insulin sensitivity and improved insulin resistance in mice. Importantly, after administration, the accumulation of M1 like CD11c+ macrophages and inflammation in the liver and adipose tissue were reduced in the mice. 4-HIL also reduced the proportion of CD11c+ macrophages among bone marrow-derived macrophages, which were induced in vitro. These observations demonstrate a new role of 4-HIL in insulin resistance in hepatocytes and adipocytes. 4-HIL inhibits obesity-related insulin resistance by reducing inflammation and regulating the state of M1/M2 macrophages.

Abstract 1216: The Cardioactive Peptide Apelin Increases Adipocyte Glucose Uptake and is Necessary for the Maintenance of Systemic Insulin Sensitivity

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Patrick Yue ◽  
Tomoko Asagami ◽  
Ramendra K Kundu ◽  
Yin-Gail Yee ◽  
Alexander J Glassford ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Uptake ◽  
Embryonic Stem ◽  
Peptide Hormone ◽  
Wild Type ◽  
Glucose Levels ◽  
Glucose Tolerance Tests

Background : Apelin, a peptide hormone with unique cardioactive properties, is also an adipokine, secreted by adipocytes in response to insulin. However, the overall effect of apelin on insulin sensitivity remains largely uncharacterized. Methods : For in vitro experiments, 3T3L1 cells were differentiated into adipocytes over 8 days, with apelin (1 microM) added daily to the media. Cells were then treated with insulin (100 nM; n = 5) for 30 minutes and incubated with 2-[ 3 H]-deoxyglucose. Glucose incorporation was then measured by scintillation counting. For in vivo experiments (n = 4 all studies), apelin-deficient (KO) mice were created by homologous recombination in embryonic stem cells. At age 7 weeks, insulin and glucose tolerance tests, as well as an enzyme immunosorbent assay for insulin, were performed after a 6-hour fast. The mice were then scanned by computed tomography using a GE eXplore RS MicroCT system, and visceral adipose content was determined with MicroView software. Upon sacrifice 1 week later, visceral adipocytes were isolated via collagenase digestion, exposed to insulin, and assessed for glucose uptake as above. Results : Because apelin is upregulated by insulin in adipocytes, we measured glucose uptake in differentiated 3T3L1 cells chronically dosed with apelin. Though no differences were observed in basal uptake, insulin-induced uptake was increased versus control (p < 0.05). To further investigate the role of apelin in vivo , we assessed for insulin resistance in apelin KO mice. At 8 weeks of age, apelin KOs were heavier than age-matched wild type controls (25 vs. 22 g; p < 0.05). Though fasting glucose levels were not significantly different between groups, insulin levels were increased in the KOs (895 vs. 477 pg/microL; p < 0.05). In addition, both insulin and glucose tolerance tests were significantly abnormal in the KOs compared to wild type. Moreover, visceral fat volume was greater in the KOs (274 vs. 248 mm 3 /g body weight; p < 0.05). Finally, insulin-stimulated uptake was reduced (p < 0.05). Conclusions : Apelin is necessary for the proper maintenance of glucose homeostasis. Furthermore, apelin potentiates insulin-induced glucose uptake in adipocytes, suggesting a possible mechanism for its insulin sensitizing effects.

Effects of pioglitazone and metformin on β-cell function in nondiabetic subjects at high risk for type 2 diabetes

2007 ◽  
Vol 292 (1) ◽  
pp. E359-E365 ◽  
Author(s):  
Neda Rasouli ◽  
Philip A Kern ◽  
E. Albert Reece ◽  
Steven C. Elbein
Keyword(s):  
At Risk ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Glucose Disposal ◽  
Β Cell ◽  
Intravenous Glucose ◽  
Glucose Levels ◽  
Β Cell Function

Thiazolidinediones (TZDs) and metformin decreased the incidence of diabetes in subjects at risk for developing diabetes and improved peripheral or hepatic insulin sensitivity, respectively. Whether they also directly improved β-cell function is not clear. In vitro studies showed improved β-cell function in response to TZDs and metformin; however, the effects of TZDs or metformin on β-cell function in humans are still uncertain. We hypothesized that both TZDs and metformin directly affect β-cell function. We evaluated β-cell function and insulin sensitivity (SI) in subjects with impaired glucose tolerance or a history of gestational diabetes using oral and intravenous glucose tolerance tests in addition to the glucose-potentiated arginine stimulation test. In contrast to metformin, pioglitazone improved SI, glucose tolerance, and insulin-independent glucose disposal [glucose effectiveness (SG)]. Neither pioglitazone nor metformin significantly improved β-cell compensation for insulin resistance [disposition index (DI)], but the change in DI significantly correlated with baseline SI. Insulin secretion in response to arginine at maximally potentiating glucose levels (AIRmax) tended to increase after metformin and to decrease after pioglitazone; however, when adjusted for SI, the changes were not significant. Our results demonstrate that, in nondiabetic subjects at risk for diabetes, pioglitazone, but not metformin, significantly improved glucose tolerance by improving SI and SG. We did not find any evidence that either pioglitazone or metformin improved β-cell function. Improved β-cell compensation was observed primarily in the subgroup of subjects that had the lowest SI at baseline.

scholarly journals G Protein-Coupled Receptor 39 Deficiency Is Associated with Pancreatic Islet Dysfunction

Endocrinology ◽  
2009 ◽  
Vol 150 (6) ◽  
pp. 2577-2585 ◽  
Author(s):  
Birgitte Holst ◽  
Kristoffer L. Egerod ◽  
Chunyu Jin ◽  
Pia Steen Petersen ◽  
Mette Viberg Østergaard ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Pancreatic Islets ◽  
G Protein ◽  
Insulin Response ◽  
Oral Glucose ◽  
G Protein Coupled Receptor ◽  
Pancreatic Cell ◽  
G Protein Coupled

G protein-coupled receptor (GPR)-39 is a seven-transmembrane receptor expressed mainly in endocrine and metabolic tissues that acts as a Zn++ sensor signaling mainly through the Gq and G12/13 pathways. The expression of GPR39 is regulated by hepatocyte nuclear factor (HNF)-1α and HNF-4α, and in the present study, we addressed the importance of GPR39 for glucose homeostasis and pancreatic islets function. The expression and localization of GPR39 were characterized in the endocrine pancreas and pancreatic cell lines. Gpr39(−/−) mice were studied in vivo, especially in respect of glucose tolerance and insulin sensitivity, and in vitro in respect of islet architecture, gene expression, and insulin secretion. Gpr39 was down-regulated on differentiation of the pluripotent pancreatic cell line AR42J cells toward the exocrine phenotype but was along with Pdx-1 strongly up-regulated on differentiation toward the endocrine phenotype. Immunohistochemistry demonstrated that GRP39 is localized selectively in the insulin-storing cells of the pancreatic islets as well as in the duct cells of the exocrine pancreas. Gpr39(−/−) mice displayed normal insulin sensitivity but moderately impaired glucose tolerance both during oral and iv glucose tolerance tests, and Gpr39(−/−) mice had decreased plasma insulin response to oral glucose. Islet architecture was normal in the Gpr39 null mice, but expression of Pdx-1 and Hnf-1α was reduced. Isolated, perifused islets from Gpr39 null mice secreted less insulin in response to glucose stimulation than islets from wild-type littermates. It is concluded that GPR39 is involved in the control of endocrine pancreatic function, and it is suggested that this receptor could be a novel potential target for the treatment of diabetes.

scholarly journals Identification of Multiple Pancreatic and Extra-Pancreatic Pathways Underlying the Glucose-Lowering Actions of Acacia arabica Bark in Type-2 Diabetes and Isolation of Active Phytoconstituents

Plants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1190
Author(s):  
Prawej Ansari ◽  
Peter R. Flatt ◽  
Patrick Harriott ◽  
J. M. A. Hannan ◽  
Yasser H. A. Abdel-Wahab
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Β Cells ◽  
Glucose Lowering ◽  
Obese Rats ◽  
Mouse Islets ◽  
Acacia Arabica

Acacia arabica is used traditionally to treat a variety of ailments, including diabetes. This study elucidated the antidiabetic actions of A. arabica bark together with the isolation of bioactive molecules. Insulin secretion and signal transduction were measured using clonal β cells and mouse islets. Glucose uptake was assessed using 3T3-L1 adipocytes, and in vitro systems assessed additional glucose-lowering actions. High-fat-fed (HFF) obese rats were used for in vivo evaluation, and phytoconstituents were isolated and characterised by RP-HPLC followed by LC-MS and NMR. Hot-water extract of A. arabica (HWAA) increased insulin release from clonal β cells and mouse islets by 1.3–6.8-fold and 1.6–3.2-fold, respectively. Diazoxide, verapamil and calcium-free conditions decreased insulin-secretory activity by 30–42%. In contrast, isobutylmethylxanthine (IBMX), tolbutamide and 30 mM KCl potentiated the insulin-secretory effects. The mechanism of actions of HWAA involved membrane depolarisation and elevation of intracellular Ca2+ together with an increase in glucose uptake by 3T3-L1 adipocytes, inhibition of starch digestion, glucose diffusion, dipeptidyl peptidase-IV (DPP-IV) enzyme activity and protein glycation. Acute HWAA administration (250 mg/5 mL/kg) enhanced glucose tolerance and plasma insulin in HFF obese rats. Administration of HWAA (250 mg/5 mL/kg) for 9 days improved glucose homeostasis and β-cell functions, thereby improving glycaemic control, and circulating insulin. Isolated phytoconstituents, including quercetin and kaempferol, increased insulin secretion in vitro and improved glucose tolerance. The results indicate that HWAA has the potential to treat type 2 diabetes as a dietary supplement or as a source of antidiabetic agents, including quercetin and kaempferol.

Sex-dependent differences in rat hepatic lipid accumulation and insulin sensitivity in response to diet-induced obesity

2012 ◽  
Vol 90 (2) ◽  
pp. 164-172 ◽  
Author(s):  
Antònia Nadal-Casellas ◽  
Ana Maria Proenza ◽  
Isabel Lladó ◽  
Magdalena Gianotti
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Insulin Signaling ◽  
Lipid Accumulation ◽  
Dietary Treatment ◽  
Pyruvate Dehydrogenase Kinase ◽  
Female Rats ◽  
Liver Fat ◽  
Standard Diet ◽  
Fat Accumulation

Ectopic deposition of lipids in liver and other extrahepatic tissues alters their function and occurs once adipose tissue fat storage capacity is exceeded. We investigated sexual dimorphism in the effects of dietary obesity on the liver insulin signaling pathway, as well as its connection to differences in hepatic fat accumulation. Ten-week-old Wistar rats of both sexes were fed a standard diet or a high-fat diet for 26 weeks. Insulin, adipokine levels, and glucose tolerance were measured. Lipid content, PPARα mRNA expression and protein levels of insulin receptor subunit β (IRβ), IR substrate 2 (IRS-2), Ser/Thr kinase A (Akt), and pyruvate dehydrogenase kinase isozyme 4 (PDK4) were measured in liver. In control rats, serum parameters and hepatic levels of IRβ, IRS-2, and Akt proteins pointed to a profile of better insulin sensitivity in females. In response to dietary treatment, female rats exhibited a greater increase in body mass and adiposity and lower liver fat accumulation than males, but maintained better glucose tolerance. The reduced insulin signaling capacity in the liver of obese female rats seems to prevent lipid accumulation and probably lipotoxicity-associated hepatic disorders.

Sign in / Sign up

Export Citation Format

Share Document