Surrogate measures of insulin resistance: of rats, mice, and men
2009; American Physiological Society; Volume: 296; Issue: 2 Linguagem: Inglês
10.1152/ajpendo.90889.2008
ISSN1522-1555
Autores Tópico(s)Adipokines, Inflammation, and Metabolic Diseases
ResumoLETTERS TO THE EDITORSurrogate measures of insulin resistance: of rats, mice, and menKieren MatherKieren MatherPublished Online:01 Feb 2009https://doi.org/10.1152/ajpendo.90889.2008MoreSectionsPDF (41 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat to the editor: In studies of human metabolic physiology a number of surrogate measures of insulin resistance have been proposed, and their relationships to formal measures of whole body insulin sensitivity made by classical insulin-glucose clamp measures have been assessed (2, 8, 11, 13, 20, 22, 23, 30, 32). The most prominent of these at present are the homeostasis model index of insulin resistance {HOMA-IR; [insulin (in mU/l) × glucose(in mmol/l)/22.5]}, and the quantitative insulin check index of insulin sensitivity {QUICKI; 1/[log(insulin) + log(glucose)]} (7, 23, 25, 34). These two indexes were independently derived using empirical methods and are mathematically strongly related to each other (27). One notable difference is that the HOMA-IR index incorporates a normalizing factor that is specific to its application in human subjects, having been derived and validated in humans. Other indexes in common use include fasting insulin concentrations (usually analyzed as 1/insulin), and the Matsuda and Stumvoll indexes (22, 30). The addition of dynamic (i.e., OGTT-derived) components can add information about β-cell responsiveness to the measures of fasting and post-load insulin responses, but with less specificity than would be available from mathematical modeling to separate these components (as is done in modeling the dynamic response to a glucose load in the Bergman minimal model, for example). Ultimately, the simplest and least confounded indexes remain the HOMA and QUICKI models. The strength of these measures as surrogates relies on the strength of the underlying physiological relationship between hepatic insulin responses (i.e., suppression of hepatic glucose production by insulin under fasting conditions) and whole body insulin responses measured with clamp procedure (largely reflecting skeletal muscle insulin responsiveness). Multiple investigators have demonstrated strong correlations (r values 0.6–0.8) between these surrogates and clamp-based measures (3, 7, 9, 11, 16, 20). Furthermore, shifts in these surrogates with interventions that shift clamp-based measurements of insulin resistance (20, 21, 29, 31) confirm their utility in epidemiologic and clinical trial applications in the study of human disease.The study of metabolic abnormalities in animal models contributes importantly to advances in our understanding of the physiology and pathophysiology of obesity, insulin resistance, and diabetes. In animal models, some aspects of metabolic function are available for direct measurement (e.g., ex vivo measurement of β-cell function or signaling molecule responses to insulin), but the need for intact system, whole animal measurements of physiology remains. In fact, due to the smaller blood vessel size and smaller blood volume available for sampling, the performance of classical hyperinsulinemic euglycemic clamp studies is arguably more difficult in rodents than in humans. It is therefore not surprising that there is equal interest in surrogate measures in rats and mice as in studies of humans. Although these indexes have begun to be applied in work involving rodent models (1, 5, 6, 10, 12, 14, 15, 18, 19, 24, 26, 28, 33, 35), formal assessments of the relationship of surrogate measures with clamp measures of insulin resistance in rodents are only now coming to light. One such paper was recently published in this Journal, detailing interrelationships of HOMA-IR and QUICKI with formal clamp-derived methods in Sprague-Dawley and Wistar rats (4). Another recently published paper describes analogous comparisons in mice, including standard C57BL6 mice and a selection of transgenic mice with increased or decreased endogenous insulin resistance (17).The overall result is that HOMA-IR and QUICKI as surrogate measures provide a reasonable and reliable approximation of formal measures of insulin resistance when applied to rats and mice as they do in humans. In both papers, the surrogate indexes proved adequate for demonstrating physiologically relevant differences in insulin resistance, induced by pregnancy in the study of rats and induced by fat feeding and/or transgenes in the study of mice. This is an extremely useful set of observations and validates the continued application of these surrogates in animal studies. Also, the similarities with observations in humans suggest that the relationships between fasting and insulin-stimulated measures of insulin resistance carry well across species, validating the animal models for these applications.There are interesting subtleties that limit the broad application of these indexes and therefore warrant comment. For instance, the degree of correlation with clamp measures of insulin sensitivity in the two strains of rats evaluated was of the same order as that described for humans (r = ∼0.7–0.8), but these measures were less closely correlated in mice (r = ∼0.4 compared against both glucose infusion rate and SIclamp, modestly improved by adjusting for body weight). Differences in the precision of the clamp measures in the smaller animals may have contributed to this observation. The two strains of rats studied exhibited different physiologically normal fasting glucose levels with similar insulin concentrations. Therefore, the absolute value of the "normal" value for the HOMA-IR and QUICKI differed considerably between strains, although linear relationships of indexes with clamp measurements were similar between strains. The study of mice included only one "normal" strain, so it is unclear whether such differences need to be taken into account for mice as well. In the study of rats, a species-specific normal range for HOMA-IR was applied, rather than dividing the glucose-insulin product by the human-specific constant of 22.5. Since this term is in the denominator for the HOMA-IR calculation, the use of incorrect values (or values with incorrect units) will introduce a nonlinear error. This species-specific adjustment is therefore more correct and advisable in the application of the HOMA model to nonhuman species. The QUICKI model does not incorporate such species-specific components and therefore does not require such adjustment.These points warrant consideration in the design and interpretation of studies applying these surrogate measures of insulin resistance to the study of metabolism in animal models. However they do not detract from the broader observation that, as in humans, HOMA-IR and QUICKI indexes of insulin resistance based on fasting measurements of glucose and insulin can serve as useful and reliable surrogates of more difficult and time-consuming clamp-based measurements. The formal clamp-based measures will still provide the most definitive measures where detailed physiological questions are being pursued; but with the above caveats in mind, these surrogates can be more broadly applied in animal studies where clamps are not otherwise needed.REFERENCES1 Al-Azzawi HH, Mathur A, Lu D, Swartz-Basile DA, Nakeeb A, Pitt HA. Pioglitazone increases gallbladder volume in insulin-resistant obese mice. J Surg Res 136: 192–197, 2006.Crossref | PubMed | ISI | Google Scholar2 Albareda M, Rodriguez-Espinosa J, Murugo M, de Leiva A, Corcoy R. Assessment of insulin sensitivity and beta-cell function from measurements in the fasting state and during an oral glucose tolerance test. Diabetologia 43: 1507–1511, 2000.Crossref | PubMed | ISI | Google Scholar3 Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, Monauni T, Muggeo M. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity. Diabetes Care 23: 57–63, 2000.Crossref | PubMed | ISI | Google Scholar4 Cacho J, Sevillano J, de Castro J, Herrera E, Ramos MD. Validation of simple indexes to assess insulin sensitivity during pregnancy in Wistar and Sprague Dawley rats. Am J Physiol Endocrinol Metab 295: E1269–E1276, 2008.Link | ISI | Google Scholar5 Cha DR, Han JY, Su DM, Zhang Y, Fan X, Breyer MD, Guan Y. Peroxisome proliferator-activated receptor-alpha deficiency protects aged mice from insulin resistance induced by high-fat diet. Am J Nephrol 27: 479–482, 2007.Crossref | PubMed | ISI | Google Scholar6 Chang CH, McNamara LA, Wu MS, Muise ES, Tan Y, Wood HB, Meinke PT, Thompson JR, Doebber TW, Berger JP, McCann ME. A novel selective peroxisome proliferator-activator receptor-gamma modulator-SPPARgammaM5 improves insulin sensitivity with diminished adverse cardiovascular effects. Eur J Pharmacol 584: 192–201, 2008.Crossref | PubMed | ISI | Google Scholar7 Chen H, Sullivan G, Quon MJ. Assessing the predictive accuracy of QUICKI as a surrogate index for insulin sensitivity using a calibration model. Diabetes 54: 1914–1925, 2005.Crossref | PubMed | ISI | Google Scholar8 Gutt M, Davis CL, Spitzer SB, Llabre MM, Kumar M, Czarnecki EM, Schneiderman N, Skyler JS, Marks JB. Validation of the insulin sensitivity index [ISI(0,120)]: comparison with other measures. Diabetes Res Clin Pract 47: 177–184, 2000.Crossref | PubMed | ISI | Google Scholar9 Hanson RL, Pratley RE, Bogardus C, Narayan KM, Roumain JM, Imperatore G, Fagot-Campagna A, Pettitt DJ, Bennett PH, Knowler WC. Evaluation of simple indices of insulin sensitivity and insulin secretion for use in epidemiologic studies. Am J Epidemiol 151: 190–198, 2000.Crossref | PubMed | ISI | Google Scholar10 Herbach N, Rathkolb B, Kemter E, Pichl L, Klaften M, de Angelis MH, Halban PA, Wolf E, Aigner B, Wanke R. Dominant-negative effects of a novel mutated Ins2 allele causes early-onset diabetes and severe beta-cell loss in Munich Ins2C95S mutant mice. Diabetes 56: 1268–1276, 2007.Crossref | PubMed | ISI | Google Scholar11 Holzinger U, Kitzberger R, Fuhrmann V, Funk GC, Madl C, Ratheiser K. Correlation of calculated indices of insulin resistance (QUICKI and HOMA) with the euglycaemic hyperinsulinaemic clamp technique for evaluating insulin resistance in critically ill patients. Eur J Anaesthesiol 24: 966–970, 2007.Crossref | PubMed | ISI | Google Scholar12 Josefsen K, Nielsen MD, Jorgensen KH, Bock T, Norremolle A, Sorensen SA, Naver B, Hasholt L. Impaired glucose tolerance in the R6/1 transgenic mouse model of Huntington's disease. J Neuroendocrinol 20: 165–172, 2008.Crossref | PubMed | ISI | Google Scholar13 Katz A, Sridhar SN, Albert P, Sumner AE, Quon MJ. Quantitative Insulin-Sensitivity Check Index: A simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 85: 2402–2410, 2000.Crossref | PubMed | ISI | Google Scholar14 Kim MK, Chae YN, Son MH, Kim SH, Kim JK, Moon HS, Park CS, Bae MH, Kim E, Han T, Choi HH, Shin YA, Ahn BN, Lee CH, Lim JI, Shin CY. PAR-5359, a well-balanced PPARalpha/gamma dual agonist, exhibits equivalent antidiabetic and hypolipidemic activities in vitro and in vivo. Eur J Pharmacol 595: 119–125, 2008.Crossref | PubMed | ISI | Google Scholar15 Konrad D, Rudich A, Schoenle EJ. Improved glucose tolerance in mice receiving intraperitoneal transplantation of normal fat tissue. Diabetologia 50: 833–839, 2007.Crossref | PubMed | ISI | Google Scholar16 Lansang MC, Williams GH, Carroll JS. Correlation between the glucose clamp technique and the homeostasis model assessment in hypertension. Am J Hypertens 14: 51–53, 2001.Crossref | PubMed | ISI | Google Scholar17 Lee S, Muniyappa R, Yan X, Chen H, Yue LQ, Hong EG, Kim JK, Quon MJ. Comparison between surrogate indexes of insulin sensitivity and resistance and hyperinsulinemic euglycemic clamp estimates in mice. Am J Physiol Endocrinol Metab 294: E261–E270, 2008.Link | ISI | Google Scholar18 Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, Furuyama N, Kondo H, Takahashi M, Arita Y, Komuro R, Ouchi N, Kihara S, Tochino Y, Okutomi K, Horie M, Takeda S, Aoyama T, Funahashi T, Matsuzawa Y. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 8: 731–737, 2002.Crossref | PubMed | ISI | Google Scholar19 Mao XQ, Wu Y, Wu K, Liu M, Zhang JF, Zou F, Ou-Yang JP. Astragalus polysaccharide reduces hepatic endoplasmic reticulum stress and restores glucose homeostasis in a diabetic KKAy mouse model. Acta Pharmacol Sin 28: 1947–1956, 2007.Crossref | PubMed | ISI | Google Scholar20 Mather KJ, Hunt AE, Steinberg HO, Paradisi G, Hook G, Katz A, Quon MJ, Baron AD. Repeatability characteristics of simple indices of insulin resistance: implications for research applications. J Clin Endocrinol Metab 86: 5457–5464, 2001.Crossref | PubMed | ISI | Google Scholar21 Mather KJ, Verma S, Anderson TJ. Improved endothelial function with metformin in type 2 diabetes mellitus. J Am Coll Cardiol 37: 1344–1350, 2001.Crossref | PubMed | ISI | Google Scholar22 Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22: 1462–1470, 1999.Crossref | PubMed | ISI | Google Scholar23 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and B cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28: 412–419, 1985.Crossref | PubMed | ISI | Google Scholar24 Moloney F, Toomey S, Noone E, Nugent A, Allan B, Loscher CE, Roche HM. Antidiabetic effects of cis-9, trans-11-conjugated linoleic acid may be mediated via anti-inflammatory effects in white adipose tissue. Diabetes 56: 574–582, 2007.Crossref | PubMed | ISI | Google Scholar25 Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab 294: E15–E26, 2008.Link | ISI | Google Scholar26 Potenza MA, Marasciulo FL, Tarquinio M, Quon MJ, Montagnani M. Treatment of spontaneously hypertensive rats with rosiglitazone and/or enalapril restores balance between vasodilator and vasoconstrictor actions of insulin with simultaneous improvement in hypertension and insulin resistance. Diabetes 55: 3594–3603, 2006.Crossref | PubMed | ISI | Google Scholar27 Radziuk J. Insulin sensitivity and its measurement: structural commonalities among the methods. J Clin Endocrinol Metab 85: 4426–4433, 2000.PubMed | ISI | Google Scholar28 Rinella ME, Green RM. The methionine-choline deficient dietary model of steatohepatitis does not exhibit insulin resistance. J Hepatol 40: 47–51, 2004.Crossref | PubMed | ISI | Google Scholar29 Sciacqua A, Candigliota M, Ceravolo R, Scozzafava A, Sinopoli F, Corsonello A, Sesti G, Perticone F. Weight loss in combination with physical activity improves endothelial dysfunction in human obesity. Diabetes Care 26: 1673–1678, 2003.Crossref | PubMed | ISI | Google Scholar30 Stumvoll M, Mitrakou A, Pimenta W, Jenssen T, Yki-Jarvinen H, Van Haeften T, Renn W, Gerich J. Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. Diabetes Care 23: 295–301, 2000.Crossref | PubMed | ISI | Google Scholar31 Tan MH, Glazer NB, Johns D, Widel M, Gilmore KJ. Pioglitazone as monotherapy or in combination with sulfonylurea or metformin enhances insulin sensitivity (HOMA-S or QUICKI) in patients with type 2 diabetes. Curr Med Res Opin 20: 723–728, 2004.Crossref | PubMed | ISI | Google Scholar32 Turner RC, Rudenski AS, Hosker JP, Matthews DR, Levy JC, O'Rahilly SP. CIGMA as a tool in the study of NIDDM. Prog Clin Biol Res 265: 13–26, 1988.PubMed | Google Scholar33 Verreth W, De Keyzer D, Pelat M, Verhamme P, Ganame J, Bielicki JK, Mertens A, Quarck R, Benhabiles N, Marguerie G, Mackness B, Mackness M, Ninio E, Herregods MC, Balligand JL, Holvoet P. Weight-loss-associated induction of peroxisome proliferator-activated receptor-alpha and peroxisome proliferator-activated receptor-gamma correlate with reduced atherosclerosis and improved cardiovascular function in obese insulin-resistant mice. Circulation 110: 3259–3269, 2004.Crossref | PubMed | ISI | Google Scholar34 Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care 27: 1487–1495, 2004.Crossref | PubMed | ISI | Google Scholar35 Xu A, Lam MC, Chan KW, Wang Y, Zhang J, Hoo RL, Xu JY, Chen B, Chow WS, Tso AW, Lam KS. Angiopoietin-like protein 4 decreases blood glucose and improves glucose tolerance but induces hyperlipidemia and hepatic steatosis in mice. Proc Natl Acad Sci USA 102: 6086–6091, 2005.Crossref | PubMed | ISI | Google Scholar Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation Cited ByBlueberry and Blackberry Anthocyanins Ameliorate Metabolic Syndrome by Modulating Gut Microbiota and Short-Chain Fatty Acids Metabolism in High-Fat Diet-Fed C57BL/6J Mice27 September 2023 | Journal of Agricultural and Food Chemistry, Vol. 71, No. 40Involvement of the Receptor for Advanced Glycation End Products (RAGE) in High Fat-High Sugar Diet-Induced Anhedonia in RatsPhysiology & Behavior, Vol. 16FoxO1 regulates adipose transdifferentiation and iron influx by mediating Tgfβ1 signaling pathwayRedox Biology, Vol. 63Insulin resistance and adipose tissue inflammation induced by a high-fat diet are attenuated in the absence of hepcidinThe Journal of Nutritional Biochemistry, Vol. 111The Effects of Aging on Male Mouse Pancreatic β-Cell Function Involve Multiple Events in the Regulation of Secretion: Influence of Insulin Sensitivity25 September 2021 | The Journals of Gerontology: Series A, Vol. 77, No. 3Long-Term Consumption of a Sugar-Sweetened Soft Drink in Combination with a Western-Type Diet Is Associated with Morphological and Molecular Changes of Taste Markers Independent of Body Weight Development in Mice29 January 2022 | Nutrients, Vol. 14, No. 3Sex and genetic background define the metabolic, physiologic, and molecular response to protein restrictionCell Metabolism, Vol. 34, No. 2Dynamic interplay between Afadin S1795 phosphorylation and diet regulates glucose homeostasis in obese mice1 September 2021 | The Journal of Physiology, Vol. 600, No. 4The effects of resistance exercise training followed by de-training on irisin and some metabolic parameters in type 2 diabetic rat model7 October 2019 | Archives of Physiology and Biochemistry, Vol. 128, No. 14-Phenylbutyrate (PBA) treatment reduces hyperglycemia and islet amyloid in a mouse model of type 2 diabetes and obesity4 June 2021 | Scientific Reports, Vol. 11, No. 1Novel Sesquiterpene Glycoside from Loquat Leaf Alleviates Type 2 Diabetes Mellitus Combined with Nonalcoholic Fatty Liver Disease by Improving Insulin Resistance, Oxidative Stress, Inflammation, and Gut Microbiota Composition16 November 2021 | Journal of Agricultural and Food Chemistry, Vol. 69, No. 47Associations Between Betatrophin with Irisin and Metabolic Factors: Effects of Two Exercise Trainings in Diabetic RatsThe American Journal of the Medical Sciences, Vol. 362, No. 5Adipocyte CAMK2 deficiency improves obesity-associated glucose intoleranceMolecular Metabolism, Vol. 53Tissue-Specific Splicing and Dietary Interaction of a Mutant As160 Allele Determine Muscle Metabolic Fitness in Rodents12 May 2021 | Diabetes, Vol. 70, No. 8Environmental cadmium exposure during pregnancy causes diabetes-like phenotypes in mouse offspring: Association with oxidative stress in the fetal liverScience of The Total Environment, Vol. 777Virilizing doses of testosterone decrease circulating insulin levels and differentially regulate insulin signaling in liver and adipose tissue of femalesKadden H. Kothmann, Victoria Jacobsen, Emily Laffitte, Corinne Bromfield, Matthew Grizzaffi, Monica Jarboe, Andrea G. Braundmeier-Fleming, Janice M. Bahr, Romana A. Nowak, and Annie E. Newell-Fugate2 June 2021 | American Journal of Physiology-Endocrinology and Metabolism, Vol. 320, No. 6Quercetin Reverses Cardiac Systolic Dysfunction in Mice Fed with a High-Fat Diet: Role of AngiogenesisOxidative Medicine and Cellular Longevity, Vol. 2021A comparison of the metabolic side-effects of the second-generation antipsychotic drugs risperidone and paliperidone in animal models28 January 2021 | PLOS ONE, Vol. 16, No. 1Effect of Celery Extract on Fructose Induced Insulin Resistance Rattus norvegicus14 January 2021 | Folia Medica Indonesiana, Vol. 56, No. 4Sodium acetate-mediated inhibition of histone deacetylase alleviates hepatic lipid dysregulation and its accompanied injury in streptozotocin-nicotinamide-induced diabetic ratsBiomedicine & Pharmacotherapy, Vol. 128Dietary carbohydrates modulate metabolic and β-cell adaptation to high-fat diet-induced obesityTracy K. Her,* William S. Lagakos,* Matthew R. Brown, Nathan K. LeBrasseur, Kuntol Rakshit, and Aleksey V. Matveyenko20 May 2020 | American Journal of Physiology-Endocrinology and Metabolism, Vol. 318, No. 6The effects of myo-inositol and probiotic supplementation in a high-fat-fed preclinical model of glucose intolerance in pregnancy27 November 2019 | British Journal of Nutrition, Vol. 123, No. 5The synergistic effect of fenretinide and metformin to achieve a decrease in insulin resistance and inflammatory mediators: an in vivo study26 February 2020 | All Life, Vol. 13, No. 1Adverse effects of BMPR2 suppression in macrophages in animal models of pulmonary hypertension1 March 2020 | Pulmonary Circulation, Vol. 10, No. 1Characterization of inflammation and insulin resistance in high‐fat diet‐induced male C57BL/6J mouse model of obesity25 September 2019 | Animal Models and Experimental Medicine, Vol. 2, No. 4Significant changes in hepatic transcriptome and circulating miRNAs are associated with diet‐induced metabolic syndrome in apoE3L.CETP mice23 April 2019 | Journal of Cellular Physiology, Vol. 234, No. 11Indole-3-Acetic Acid Alleviates Nonalcoholic Fatty Liver Disease in Mice via Attenuation of Hepatic Lipogenesis, and Oxidative and Inflammatory Stress3 September 2019 | Nutrients, Vol. 11, No. 9GLP‐1 induces alpha cell proliferation and overrides leptin suppression induced by negative energy balance in vagotomized rats17 April 2019 | Journal of Cellular Biochemistry, Vol. 120, No. 9Lower cardiovagal tone and baroreflex sensitivity associated with hepatic insulin resistance and promote cardiovascular disorders in Tibetan minipigs induced by a high fat and high cholesterol dietJournal of Diabetes and its Complications, Vol. 33, No. 4Diabetes Impairs Angiogenesis and Induces Endothelial Cell Senescence by Up-Regulating Thrombospondin-CD47-Dependent Signaling4 February 2019 | International Journal of Molecular Sciences, Vol. 20, No. 3Orexin and adiponectin in high fat diet–induced insulin resistance22 October 2018 | Journal of Histotechnology, Vol. 42, No. 1Obestatin protects and reverses nonalcoholic fatty liver disease and its associated insulin resistance in rats via inhibition of food intake, enhancing hepatic adiponectin signaling, and blocking ghrelin acylation10 February 2018 | Archives of Physiology and Biochemistry, Vol. 125, No. 1Insulin Tolerance Test under Anaesthesia to Measure Tissue-specific Insulin-stimulated Glucose DisposalBIO-PROTOCOL, Vol. 9, No. 2Adverse physiologic effects of Western diet on right ventricular structure and function: role of lipid accumulation and metabolic therapy1 December 2018 | Pulmonary Circulation, Vol. 9, No. 1Possible mechanisms underlying fatty liver in a rat model of male hypogonadism: A protective role for testosteroneSteroids, Vol. 135Low- and high-protein diets do not alter ex vivo insulin action in skeletal muscle12 July 2018 | Physiological Reports, Vol. 6, No. 13Ellagic Acid Alleviates Hepatic Oxidative Stress and Insulin Resistance in Diabetic Female Rats25 April 2018 | Nutrients, Vol. 10, No. 5The Wnt Signaling Pathway Effector TCF7L2 Mediates Olanzapine-Induced Weight Gain and Insulin Resistance16 April 2018 | Frontiers in Pharmacology, Vol. 9Cholic Acid Supplementation of a High-Fat Obesogenic Diet Suppresses Hepatic Triacylglycerol Accumulation in Mice via a Fibroblast Growth Factor 21–Dependent MechanismThe Journal of Nutrition, Vol. 148, No. 4Restoration of metabolic health by decreased consumption of branched‐chain amino acids27 December 2017 | The Journal of Physiology, Vol. 596, No. 4Inactivation of SPAK kinase reduces body weight gain in mice fed a high-fat diet by improving energy expenditure and insulin sensitivityIvan Torre-Villalvazo,* Luz Graciela Cervantes-Pérez,* Lilia G. Noriega, Jose V. Jiménez, Norma Uribe, María Chávez-Canales, Claudia Tovar-Palacio, Braulio A. Marfil-Garza, Nimbe Torres, Norma A. Bobadilla, Armando R. Tovar, and Gerardo Gamba3 January 2018 | American Journal of Physiology-Endocrinology and Metabolism, Vol. 314, No. 1Evaluation of the glycemic effect of Ceratonia siliqua pods (Carob) on a streptozotocin-nicotinamide induced diabetic rat model23 May 2018 | PeerJ, Vol. 6Short-term consumption of a plant protein diet does not improve glucose homeostasis of young C57BL/6J miceNutrition and Healthy Aging, Vol. 4, No. 3The Effect of Anthocyanin-Rich Purple Vegetable Diets on Metabolic Syndrome in Obese Zucker RatsJournal of Medicinal Food, Vol. 20, No. 12Evaluating the evidence for macrophage presence in skeletal muscle and its relation to insulin resistance in obese mice and humans: a systematic review protocol8 August 2017 | BMC Research Notes, Vol. 10, No. 1The loss of P2X7 receptor expression leads to increase intestinal glucose transit and hepatic steatosis10 October 2017 | Scientific Reports, Vol. 7, No. 1Effect of miglitol on the suppression of nonalcoholic steatohepatitis development and improvement of the gut environment in a rodent model27 March 2017 | Journal of Gastroenterology, Vol. 52, No. 11Coconut Oil Aggravates Pressure Overload-Induced Cardiomyopathy without Inducing Obesity, Systemic Insulin Resistance, or Cardiac Steatosis18 July 2017 | International Journal of Molecular Sciences, Vol. 18, No. 7A novel dual amylin and calcitonin receptor agonist, KBP‐089, induces weight loss through a reduction in fat, but not lean mass, while improving food preference15 February 2017 | British Journal of Pharmacology, Vol. 174, No. 7High-fat high-sugar diet induces polycystic ovary syndrome in a rodent model†27 January 2017 | Biology of Reproduction, Vol. 96, No. 3Dihydromyricetin delays the onset of hyperglycemia and ameliorates insulin resistance without excessive weight gain in Zucker diabetic fatty ratsMolecular and Cellular Endocrinology, Vol. 439Symplocos cochinchinensis enhances insulin sensitivity via the down regulation of lipogenesis and insulin resistance in high energy diet rat modelJournal of Ethnopharmacology, Vol. 193Cardiovascular and Renal Effects of Birdseed Associated with Aerobic Exercise in RatsMedicine & Science in Sports & Exercise, Vol. 48, No. 10Treatment with Parkinsonia aculeata combats insulin resistance-induced oxidative stress through the increase in PPARγ/CuZn-SOD axis expression in diet-induced obesity mice2 July 2016 | Molecular and Cellular Biochemistry, Vol. 419, No. 1-2Parkinsonia aculeata (Caesalpineaceae) improves high-fat diet-induced insulin resistance in mice through the enhancement of insulin signaling and mitochondrial biogenesisJournal of Ethnopharmacology, Vol. 183Maternal protein restriction during pregnancy and lactation alters central leptin signalling, increases food intake, and decreases bone mass in 1 year old rat offspring16 March 2016 | Clinical and Experimental Pharmacology and Physiology, Vol. 43, No. 4Activation of Transmembrane Bile Acid Receptor TGR5 Modulates Pancreatic Islet α Cells to Promote Glucose HomeostasisJournal of Biological Chemistry, Vol. 291, No. 13Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system13 October 2015 | Aging Cell, Vol. 15, No. 1Low alpha-synuclein levels in the blood are associated with insulin resistance10 July 2015 | Scientific Reports, Vol. 5, No. 1Compared to casein, bovine lactoferrin reduces plasma leptin and corticosterone and affects hypothalamic gene expression without altering weight gain or fat mass in high fat diet fed C57/BL6J mice8 December 2015 | Nutrition & Metabolism, Vol. 12, No. 1Western-style diet induces insulin insensitivity and hyperactivity in adolescent male ratsPhysiology & Behavior, Vol. 151Histopathological changes in rat pancreas and skeletal muscle associated with high fat diet induced insulin resistance13 May 2015 | Biotechnic & Histochemistry, Vol. 90, No. 7Microvascular dysfunction in the course of metabolic syndrome induced by high-fat diet3 February 2014 | Cardiovascular Diabetology, Vol. 13, No. 1Obesity in Aging Exacerbates Blood-Brain Barrier Disruption, Neuroinflammation, and Oxidative Stress in the Mouse Hippocampus: Effects on Expression of Genes Involved in Beta-Amyloid Generation and Alzheimer's Disease22 November 2013 | The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, Vol. 69, No. 10An Evaluation of the Effects of the Novel Antipsychotic Drug Lurasidone on Glucose Tolerance and Insulin Resistance: A Comparison with Olanzapine25 September 2014 | PLoS ONE, Vol. 9, No. 9Symplocos cochinchinensis attenuates streptozotocin-diabetes induced pathophysiological alterations of liver, kidney, pancreas and eye lens in ratsExperimental and Toxicologic Pathology, Vol. 66, No. 7METABOLIC PHENOTYPING GUIDELINES: Assessing glucose homeostasis in rodent modelsJournal of Endocrinology, Vol. 222, No. 3A novel oral dual amylin and calcitonin receptor agonist (KBP-042) exerts antiobesity and antidiabetic effects in ratsKim V. Andreassen*, Michael Feigh*, Sara T. Hjuler, Sofie Gydesen, Jan Erik Henriksen, Henning Beck-Nielsen, Claus Christiansen, Morten A. Karsdal, and Kim Henriksen1 July 2014 | American Journal of Physiology-Endocrinology and Metabolism, Vol. 307, No. 1Association of dietary factors with insulin resistance and inflammatory markers in subjects with diabetes mellitus and coronary artery disease in Indian populationJournal of Diabetes and its Complications, Vol. 28, No. 4Ameliorative Potential of Tamarindus indica on High Fat Diet Induced Nonalcoholic Fatty Liver Disease in RatsThe Scientific World Journal, Vol. 2014Insulin Resistance and Environmental Pollutants: Experimental Evidence and Future PerspectivesEnvironmental Health Perspectives, Vol. 121, No. 11-12Vitamin A supplementation in early life affects later response to an obesogenic diet in rats4 December 2012 | International Journal of Obesity, Vol. 37, No. 9Induction of Cytosolic Phospholipase A2α Is Required for Adipose Neutrophil Infiltration and Hepatic Insulin Resistance Early in the Course of High-Fat Feeding15 August 2013 | Diabetes, Vol. 62, No. 9Young and old genetically heterogeneous HET 3 mice on a rapamycin diet are glucose intolerant but insulin sensitive7 June 2013 | Aging Cell, Vol. 12, No. 4Effect of Crocin on the Insulin Resistance and Lipid Profile of Streptozotocin‐Induced Diabetic Rats5 September 2012 | Phytotherapy Research, Vol. 27, No. 7Both Transient and Continuous Corticosterone Excess Inhibit Atherosclerotic Plaque Formation in APOE*3-Leiden.CETP Mice22 May 2013 | PLoS ONE, Vol. 8, No. 5Differential effects of high-fat-diet rich in lard oil or soybean oil on osteopontin expression and inflammation of adipose tissue in diet-induced obese rats31 July 2012 | European Journal of Nutrition, Vol. 52, No. 3Metabolic Side-Effects of the Novel Second-Generation Antipsychotic Drugs Asenapine and Iloperidone: A Comparison with Olanzapine9 January 2013 | PLoS ONE, Vol. 8, No. 1In vivo imaging of lipid storage and regression in diet-induced obesity during nutrition manipulationAbdel Wahad Bidar, Karolina Ploj, Christopher Lelliott, Karin Nelander, Maria Sörhede Winzell, Gerhard Böttcher, Jan Oscarsson, Leonard Storlien, and Paul D. Hockings1 December 2012 | American Journal of Physiology-Endocrinology and Metabolism, Vol. 303, No. 11A study on the short-term effect of cafeteria diet and pioglitazone on insulin resistance and serum levels of adiponectin and ghrelinBrazilian Journal of Medical and Biological Research, Vol. 45, No. 10Role of adipose and hepatic atypical protein kinase C lambda (PKCλ) in the development of obesity and glucose intolerance20 October 2014 | Adipocyte, Vol. 1, No. 4Metabolic effects of benzylidene thiazolidinedione derivatives in high-fat fed mice9 August 2011 | Medicinal Chemistry Research, Vol. 21, No. 9The use of animal models in diabetes research8 May 2012 | British Journal of Pharmacology, Vol. 166, No. 3Adverse Fetal and Neonatal Outcomes Associated with a Life-Long High Fat Diet: Role of Altered Development of the Placental Vasculature19 March 2012 | PLoS ONE, Vol. 7, No. 3Elucidation of thrifty features in adult rats exposed to protein restriction during gestation and lactationPhysiology & Behavior, Vol. 105, No. 5Preventing Phosphorylation of Sterol Regulatory Element-Binding Protein 1a by MAP-Kinases Protects Mice from Fatty Liver and Visceral Obesity27 February 2012 | PLoS ONE, Vol. 7, No. 2Liver-Specific Expression of Transcriptionally Active SREBP-1c Is Associated with Fatty Liver and Increased Visceral Fat Mass21 February 2012 | PLoS ONE, Vol. 7, No. 2Prevalence and Clinical Predictors of Insulin Resistance in Reproductive-Aged Thai Women with Polycystic Ovary SyndromeInternational Journal of Endocrinology, Vol. 2012High-fat diet based on dried bovine brain: an effective animal model of dyslipidemia and insulin resistance25 March 2011 | Journal of Physiology and Biochemistry, Vol. 67, No. 3 More from this issue > Volume 296Issue 2February 2009Pages E398-E399 Copyright & PermissionsCopyright © 2009 the American Physiological Societyhttps://doi.org/10.1152/ajpendo.90889.2008PubMed19171846History Published online 1 February 2009 Published in print 1 February 2009 Metrics
Referência(s)