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Metabolic Assays

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Healy, J.A., Nilsson, K.R., Hohmeier, H.E., Berglund, J., Davis, J., Hoffman, J., Kohler, M., Li, .LS., Berggren, P.O., Newgard, C.B., Bennett, V. (2010) Cholinergic augmentation of insulin release requires ankyrin-B. Sci Signal. Vol. 3(113):ra19.

Type 2 diabetes, inositol trisphosphate receptor (IP3R)



Analytes tested using MSD® assays: Active GLP-1
Matrix tested: Mouse serum
Summary: In this paper, the authors studied the effect of ankyrin-B on insulin secretion both in vitro (targeted knockdown and rescue experiments) and in vivo (animal model) and demonstrated that ankyrin-B is necessary for full cholinergic stimulation of insulin secretion.
Read, P.A., Khan, F.Z., Heck, P.M., Hoole, S.P., Dutka, D.P. (2010) DPP-4 Inhibition by Sitagliptin Improves the Myocardial Response to Dobutamine Stress and Mitigates Stunning in a Pilot Study of Patients with Coronary Artery Disease. Circ Cardiovasc Imaging. Vol. 3(2):195-201.

Glucagon like peptide 1, coronary disease, ischemia



Analytes tested using MSD assays: GLP-1
Matrix tested: Human plasma
Summary: This study tested whether the increase in the plasma concentration of GLP-1 would protect the heart against post-ischemic left ventricular dysfunction and improve the myocardial response in patients with significant coronary artery disease.
Sauvé, M., Ban, K., Momen, M.A., Zhou, Y.Q., Henkelman, R.M., Husain, M., Drucker, D.J. (2010) Genetic deletion or pharmacological inhibition of dipeptidyl peptidase-4 improves cardiovascular outcomes following myocardial infarction in mice. Diabetes. Vol. 59(4):1063-73.

Type 2 Diabetes



Analytes tested using MSD assays: GLP-1 (7-36) amide
Matrix tested: Mouse plasma
Summary: This study was designed to examine the importance of DPP-4 for cardiovascular biology in Dpp4-/- mice, and in wild type diabetic mice subjected to experimental myocardial infarction and treated with the DPP-4 inhibitor sitagliptin.
Sugimoto, H., Okada, K., Shoda, J., Warabi, E., Ishige, K., Ueda, T., Taguchi, K., Yanagawa, T., Nakahara, A., Hyodo, I., Ishii, T., Yamamoto, M. (2010) Deletion of nuclear factor-E2-related factor-2 leads to rapid onset and progression of nutritional steatohepatitis in mice. Am J Physiol Gastrointest Liver Physiol. Vol. 298(2):G283-94.

Monocyte chemoattractant protein



Analytes tested using MSD assays: Adiponectin, MCP-1
Matrix tested: Mouse serum
Summary: The focus of this study was to determine the role of Nrf2 (nuclear factor-E2-related factor-2) in defense against nutritional steatohepatitis by comparing wild-type (WT) and Nrf2 gene-null (Nrf2-null) mice fed with methionine- and choline-deficient diet.
Tai, E.S., Tan, M.L., Stevens, R.D., Low, Y.L., Muehlbauer, M.J., Goh, D.L., Ilkayeva, O.R., Wenner, B.R., Bain, J.R., Lee, J.J., Lim, S.C., Khoo, C.M., Shah, S.H., Newgard, C.B. (2010) Insulin resistance is associated with a metabolic profile of altered protein metabolism in Chinese and Asian-Indian men. Diabetologia. Vol. 53(4):757-67.

Interleukin, IFN-g, IFNg, IFNgamma, IFNg, IFN-g, interferon, IL-1ß, IL1ß, IL1beta, IL-1b, IL1b, IL2, IL6, IL10, IL12p70, IL12-p70, TNF-a, TNFa, TNFalpha, TNF-a, TNFa



Analytes tested using MSD assays: Adiponectin, IL-1beta, IFN-gamma, IL-2, IL-6, IL-8, IL-10, IL-12p70, TNF-alpha
Matrix tested: Human serum
Summary: In this study, detailed metabolic, cytokine, hormonal and amino acid profiling of non-obese patients suffering from different degrees of insulin resistance (IR) was done to identify the metabolic events associated with IR.
Bode, F.J., Stephan, M., Wiehager, S., Nguyen, H.P., Björkqvist, M., von Hörsten, S., Bauer, A., Petersén, A. (2009) Increased numbers of motor activity peaks during light cycle are associated with reductions in adrenergic alpha(2)-receptor levels in a transgenic Huntington's disease rat model. Behav Brain Res. Vol. 205(1):175-82.

neurodegeneration



Analytes tested using MSD assays: Leptin
Matrix tested: Transgenic rat serum
Summary: In this study, disrupted circadian rhythms and sleep-wake cycle associated with Huntington’s disease were investigated in a transgenic rat model. Additionally, different sleep-regulating factors in brain areas which are involved in the regulation of the day-night cycle were assessed.
Fujita, Y., Wideman, R.D., Speck, M., Asadi, A., King, D.S., Webber, T.D., Haneda, M., Kieffer, T.J. (2009) Incretin release from gut is acutely enhanced by sugar but not by sweeteners in vivo. Am J Physiol Endocrinol Metab. Vol. 296(3):E473-9.

sugar sensing, glucose dependent insulinotropic polypeptide, glucagon-like peptide-1



Analytes tested using MSD assays: Total GLP-1
Matrix tested: Rat plasma
Summary: This study used intraperitoneal glucose tolerance tests (IPGTTs) in combination with oral sweetener administration in rats to determine whether glucose excursions were improved in response to oral sweeteners, and whether GIP and GLP-1 were released in response to oral sweeteners.
Ghanayem, B.I., Bai, R., Kissling, G.E., Travlos, G., Hoffler, U. (2009) Diet-induced obesity in male mice is associated with reduced fertility and potentiation of acrylamide-induced reproductive toxicity. Biol. Reprod. Vol. 82(1):96-104.

diet-induced obesity, hyperinsulinemia, insulin, leptin



Analytes tested using MSD assays: Leptin
Matrix tested: Mouse serum
Summary: The effect of obesity on fertility has been investigated in C57BI/6J mice in this paper.
Hoffler, U., Hobbie, K., Wilson R., Bai, R., Rahman, A., Malarkey, D., Travlos, G., Ghanayem B.I. (2009) Diet-induced obesity is associated with hyperleptinemia, hyperinsulinemia, hepatic steatosis, and glomerulopathy in C57Bl/6J mice. Endocrine. Vol. 36(2):311-25.

Diet-induced obesity, Hyperinsulinemia, Hyperleptinemia, Diabetes, Hepatic steatosis, Glomerulopathy



Analytes tested using MSD assays: Leptin, Insulin
Matrix tested: Mouse serum
Summary: In this study, the temporal progression of obesity and type 2 diabetes through sustained consumption of a high-fat diet was investigated in a genetically intact obese mouse model, C57BI/6J.
Kleiner, S., Nguyen-Tran, V., Baré, O., Huang, X., Spiegelman, B., Wu, Z. (2009) PPAR-delta agonism activates fatty acid oxidation via PGC-1alpha but does not increase mitochondrial gene expression and function. J. Biol. Chem. Vol. 284(28):18624-18633.
Analytes tested using MSD assays: Insulin
Matrix tested: Mouse plasma
Summary: The focus of this study was to determine the effect of selective PPARd agonism with the synthetic ligand, GW501516, on fatty acid oxidation and mitochondrial gene expression in vitro and in vivo.
Koppe, S.W., Elias, M., Moseley, R.H., Green, R.M. (2009) Trans fat feeding results in higher serum alanine aminotransferase and increased insulin resistance compared with a standard murine high-fat diet. Am J Physiol Gastrointest Liver Physiol. Vol. 297(2):G378-84.

non-alcoholic fatty liver disease, interleukin, IL1b, IL-1b, IL-1ß, IL1ß, IL1beta, trans fat



Analytes tested using MSD assays: Insulin, Leptin, IL-1beta
Matrix tested: Mouse serum and liver homogenates
Summary: This study compared the effects of a murine diet high in trans-fat to a standard high-fat diet that is devoid of trans-fats but high in saturated fats on experimental fatty liver disease.
Lauffer, L.M., Iakoubov, R., Brubaker, P.L. (2009) GPR119 is essential for oleoylethanolamide-induced glucagon-like peptide-1 secretion from the intestinal enteroendocrine L-cell. Diabetes. Vol. 58(5):1058-66.

Glucagon like peptide 1, insulin



Analytes tested using MSD assays: GLP-1
Matrix tested: Rat plasma
Summary: This study testing whether the long-chain fatty acid derivate oleoylethanolamide (OEA) stimulates GLP-1 release through a GPR119-dependent mechanism.
Lien, L.F., Haqq, A.M., Arlotto, M., Slentz, C.A., Muehlbauer, M.J., McMahon, R.L., Rochon, J., Gallup, D., Bain, J.R., Ilkayeva, O., Wenner, B.R., Stevens, R.D., Millington, D.S., Muoio, D.M., Butler, M.D., Newgard, C.B., Svetkey, L.P. (2009) The STEDMAN project: biophysical, biochemical and metabolic effects of a behavioral weight loss intervention during weight loss, maintenance, and regain. OMICS. Vol. 13(1):21-35.

PYY, Leptin, IL-6, IL6, IL-10, IL10, TNFalpha, TNF-alpha, insulin, C-peptide, glucagon, ghrelin, adiponectin



Analytes tested using MSD assays: Total GLP-1
Matrix tested: Human plasma
Summary: This paper provides the results of the STEDMAN project which is based on comprehensive metabolic profiling of humans to determine the biochemical mechanisms of weight loss. Metabolic and cytokine profiles of 27 subjects put on an intensive 6-month weight loss program, followed by 6-month weight gain were studied.
Lim, G.E., Huang, G.J., Flora, N., Leroith, D., Rhodes, C.J., Brubaker, P.L. (2009) Insulin regulates glucagon-like peptide-1 secretion from the enteroendocrine L cell. Endocrinology. Vol. 150(2):580-91.

insulin, insulin resistance, GLP-1, ERK1/2, secretion



Analytes tested using MSD assays: Active GLP-1 (7-36) amide
Matrix tested: Mouse plasma
Summary: This study tested whether intestinal L cells are sensitive to the effects of insulin, and whether insulin resistance in the L cell directly impairs the secretion of GLP-1. The models of GLP-1 secretion used were murine GLUTag cells, human NCI-H716 cells, fetal rat intestinal cultures, and insulin resistant MKR mice.
Meirelles, K., Ahmed, T., Culnan, D.M., Lynch, C.J., Lang, C.H., Cooney, R.N. (2009) Mechanisms of glucose homeostasis after Roux-en-Y gastric bypass surgery in the obese, insulin-resistant Zucker rat. Ann Surg. Vol. 249(2):277-85.

Glucose tolerance, obesity, diabetes, incretin, glucagon-like peptide 1, GLP-1



Analytes tested using MSD assays: Glucagon
Matrix tested: Rat plasma
Summary: This study was designed to examine the effects of the Roux-en-Y gastric bypass (RYGB) on body weight, adipose tissue depots, glucose tolerance, insulin sensitivity, and incretin production.
Suarez-Pinzon, W.L., Cembrowski, G.S. and Rabinovitch, A. (2009) Combination therapy with a dipeptidyl peptidase-4 inhibitor and a proton pump inhibitor restores normoglycaemia in non-obese diabetic mice. Diabetologia. Vol. 52(8): 1680-1682.

Type 1 diabetes, Glucagon-like peptide 1, Dipeptidyl peptidase 4



Analytes tested using MSD assays: Active GLP-1 (7-36) amide
Matrix tested: Mouse plasma
Summary: The aim of this study was to determine whether combination therapy with a DPP-4 inhibitor (raises endogenous levels of GLP-1), together with a proton pump inhibitor (raises endogenous levels of gastrin), could reverse diabetes in non-obese diabetic (NOD) mice.
Lambert, G., Ancellin, N., Charlton, F., Comas, D., Pilot, J., Keech, A., Patel, S., Sullivan, D.R., Cohn, J.S., Rye, K.A., Barter, P.J. (2008) Plasma PCSK9 Concentrations Correlate with LDL and Total Cholesterol in Diabetic Patients and Are Decreased by Fenofibrate Treatment. Clin Chem. Vol. 54:1038-1045.

Proprotein convertase subtilisin / kexin, cholesterol, diabetes



Analytes tested using MSD assays: Customer developed assay for recombinant protein
Matrix tested: Purified recombinant protein in buffer
Summary: The aim of this study was to determine whether fenofibrate (PPARa agonist drug used to decrease plasma triglycerides) modulates plasma PCSK9 concentrations in humans. Circulating levels of PCSK9 were measured in a cohort of 115 diabetic individuals before and after fenofibrate treatment.
Lan, H., Hoos, L.M., Liu, L., Tetzloff, G., Hu, W., Abbondanzo, S.J., Vassileva, G., Gustafson, E.L., Hedrick, J.A., Davis, H.R. (2008) Lack of FFAR1/GPR40 Does Not Protect Mice From High-Fat Diet–Induced Metabolic Disease. Diabetes. Vol. 57(11):2999-3006.

Fatty acid, insulin, G-protein



Analytes tested using MSD assays: Insulin, GLP-1 (7-36) amide
Matrix tested: Mouse plasma
Summary: This study investigated the metabolic phenotypes of Ffar1-/- mice to better understand the physiological role of FFAR1 in fatty acid–mediated insulin secretion.
Ning, Y, O'Neill, K, Lan, H, Pang, L, Shan, L.X., Hawes B.E., Hedrick, J.A. (2008) Endogenous and synthetic agonists of GPR119 differ in signaling pathways and their effects on insulin secretion in MIN6c4 insulinoma cells. Br J Pharmacol. Vol. 155(7):1056-65.

G-protein, GLP-1, insulin secretion, cAMP



Analytes tested using MSD assays: Insulin
Matrix tested: Cell culture supernatants
Summary: The focus of this paper is to study the underlying mechanisms of GPR119 induced insulin secretion and the potential uses of synthetic agonists. GPR119 is a G-protein coupled receptor that is preferentially expressed in pancreatic islet cells and is responsible for mediating insulin secretion.
Scheja, L., Hesse, B., Heike, Z., Michael, M.D., Siesky, A.M., Pospisil, H, Beisiegel, U., Seedorf, K. (2008) Acute-Phase Serum Amyloid A as a Marker of Insulin Resistance in Mice. Experimental Diabetes Research. Vol. 2008:230837.
Analytes tested using MSD assays: Insulin
Matrix tested: Mouse plasma
Summary: The aim of this study was to determine the mechanisms linking elevated plasma Acute-phase serum amyloid A (A-SAA) levels to insulin resistance.
Scheja, L., Toedter, K., Mohr, R., Niederfellner, G., Michael, M.D., Meissner, A., Schoettler, A., Pospisil, H., Beisiegel, U., Heeren, J. (2008) Liver TAG transiently decreases while PL n-3 and n-6 fatty acids are persistently elevated in insulin resistant mice. Lipids. Vol. 43(11):1039-51.

High fat diet, Obesity, Diabetes, Liver steatosis



Analytes tested using MSD assays: Insulin
Matrix tested: Mouse plasma
Summary: The focus of this study was to generate detailed lipid and fatty acid profiles in mice made insulin resistant by means of a HFD to elucidate changes in fatty acid metabolism associated with insulin resistance.
Waddleton, D., Wu, W., Feng, Y., Thompson, C., Wu, M., Zhou, Y.P., Howard, A., Thornberry, N., Li, J., Mancini, J.A. (2008) Phosphodiesterase 3 and 4 comprise the major cAMP metabolizing enzymes responsible for insulin secretion in INS-1 (832/13) cells and rat islets. Biochem Pharmacol. Vol. 76(7):884-93.

cAMP, Pancreatic islets, Type 2 diabetes



Analytes tested using MSD assays: Insulin
Matrix tested: Rat insulinoma cell (INS-1) culture supernatants
Summary: The aim of this study was to determine which specific phosphodiesterase enzyme family members are responsible for c-AMP mediated secretion of insulin from INS-1 cells and rat islets.
Bolten, C. W., Blanner, P.M., McDonald, W.G., Staten, N.R., Mazzarella, R.A., Arhancet, G.B., Meier, M.F., Weiss, D.J., Sullivan, P.M., Hromockyj, A.E., Kletzien, R.F., Colca, J.R. (2007) Insulin Sensitizing Pharmacology of Thiazolidinediones Correlates with Mitochondrial Gene Expression rather than Activation of PPARg. Gene Regulation and Systems Biology. Vol. 1:73-82.

thiazolidinedione, insulin sensitization, diabetes



Analytes tested using MSD assays: Phospho Akt (Ser473) / Total Akt
Matrix tested: Human hepatoma (HUH7) cell lysates
Summary: This study compares the general effects of two thiazolidinedione (TZD) analogs that vary in their ability to activate PPARg in an effort to determine the mechanisms necessary for the pharmacology of these compounds and the transcriptional regulation that are correlated with insulin sensitization.
Briscoe, C.P., Looper, D., Tran, P., Herrera, J., McDonnell, S.R., Bhat, B.G. (2007) LPS-induced biomarkers in mice: a potential model for identifying insulin sensitizers. Biochem Biophys Res Commun. Vol. 361(1):140-5.

Fatty acid, insulin, G-protein, interleukin, IL6, IL12p40, IL12-p40, TNF-a, TNFa, TNF-a, TNF a, TNFalpha, monocyte chemoattractant protein


Analytes tested using MSD assays: Phospho c-Jun, Phospho S6RP (Ser235/236), MCP-1, IL-6, IL-12p40, TNF-alpha, Insulin
Matrix tested: Mouse plasma, liver and fat tissue homogenates
Summary: This paper describes a method to create an acute in vivo insulin resistant model by administration of LPS in C57BL/6 mice.
Funicello, M., Novelli, M., Ragni, M., Vottari, T., Cocuzza, C., Soriano-Lopez, J., Chiellini, C., Boschi, F., Marzola, P., Masiello, P., Saftig, P., Santini, F., St-Jacques, R., Desmarais, S., Morin, N., Mancini, J., Percival, M.D., Pinchera, A., Maffei, M. (2007) Cathepsin K null mice show reduced adiposity during the rapid accumulation of fat stores. PLoS ONE. Vol. 2(1):683.

white adipose tissue, high fat diet


Analytes tested using MSD assays: Insulin, Leptin
Matrix tested: Mouse plasma
Summary: In this paper, the fat tissue and the metabolic phenotype of cysteine protease cathepsin K (ctsk) deficient mice have been characterized to gain a better understanding of its role in the regulation of fat storage and obesity.
Yang, R., Wilcox, D.M., Haasch, D.L., Jung, P.M., Nguyen, P.T., Voorbach, M.J., Doktor, S., Brodjian, S., Bush, E.N., Lin, E., Jacobson, P.B., Collins, C.A., Landschulz, K.T., Trevillyan, J.M., Rondinone, C.M., Surowy, T.K. (2007) Liver-specific knockdown of JNK1 up-regulates proliferator-activated receptor gamma coactivator 1 beta and increases plasma triglyceride despite reduced glucose and insulin levels in diet-induced obese mice. J Biol Chem. Vol. 282(31):22765-74.

Glycolysis, gluconeogenesis, obesity, liver, insulin resistance, Akt, Western blot


Analytes tested using MSD assays: Phospho c-Jun
Matrix tested: Mouse liver homogenates
Summary: In this study, RNA interference was done to investigate the specific role of hepatic JNK1 in contributing to insulin resistance in diet induced obese (DIO) mice.

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