Diabetologie und Stoffwechsel 2010; 5 - P94
DOI: 10.1055/s-0030-1253822

Effects of insulin on plasma metabolome and subcutaneous fat tissue transcriptome in humans

NN Rudovich 1, 2, VJ Nikiforova 3, 4, O Pivovarova 1, 2, A Erban 3, Ö Gögebakan 1, 2, AFH Pfeiffer 1, 2
  • 1German Institute of Human Nutrition Potsdam, Clinical Nutrition, Nuthetal, Germany
  • 2Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Endocrinology, Diabetes and Nutrition, Berlin, Germany
  • 3Max Planck Institute of Molecular Plant Physiology, Potsdam-Golm, Germany
  • 4Timiryazev Institute of Plant Physiology, Moscow, Russian Federation

Aims: Insulin, the dominant anabolic hormone, suppresses endogenous glucose production, stimulates glucose utilization by insulin-sensitive tissues and inhibits the lipolysis in fat. Few studies describe insulin-dependent transcriptome changes and no data exist for metabolome. In this pilot study we examined acute insulin effects on plasma metabolites and subcutaneous adipose tissue transcriptome under clamped euglycemia and hyperglycemia.

Methods: Healthy obese men (n=14) underwent a placebo infusion test (0.9% NaCl-infusion for 4h) and/or a hyperinsulinemic, euglycemic clamp (EC), and/or a hyperinsulinemic, hyperglycemic clamp (HC). SAT biopsy and plasma samples were taken at –40min and 240min of the tests. Full human genome Agilent chips were used for transcript profiling, and GC/MS analysis was applied to get the metabolome of plasma. An explorative analysis of insulin-induced changes with calculating 240 to basal ratio was conducted. We proposed “non-changed values“ as range of 1.2 to 0.8 in these ratios with p>0.06. To evaluate a trend of changes, we estimated the proportion of up and down regulated genes and metabolites (“up-to-down ratio“).

Results: The highest insulin and blood glucose levels were observed in the HC test (p<0.001). Insulin down regulates about 16% of plasma metabolome under euglycemia, while simultaneous expressional changes are only minor. In the HC experiments, the pattern of insulin induced metabolome and adipose tissue transcriptome resembled the pattern of euglycemic clamps, but more metabolites were up-regulated.

Conclusions: Insulin down regulates big portion of plasma metabolome under euglycemia, while simultaneous expressional changes are only minor. This observation reflects possible prevalence of stoichiometric-driven changes in insulin-dependent metabolome.