Mannose is an insulin-regulated metabolite reflecting whole-body insulin sensitivity in man

  • Metabolism. 2020 Jan;102:153974. doi: 10.1016/j.metabol.2019.153974.
E Ferrannini  1 ,  M Bokarewa  2 ,  P Brembeck  3 ,  R Baboota  3 ,  S Hedjazifar  3 ,  K Andersson  2 ,  S Baldi  4 ,  B Campi  5 ,  E Muscelli  1 ,  A Saba  6 ,  I Sterner  3 ,  C Wasen  2 ,  U Smith  7
Affiliations
  • 1. C.N.R. Institute of Clinical Physiology, 56124 Pisa, Italy.
  • 2. Department of Rheumatology, University of Gothenburg, 405 30 Gothenburg, Sweden.
  • 3. Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, University of Gothenburg, 405 30 Gothenburg, Sweden.
  • 4. Department of Clinical & Experimental Medicine, University of Pisa, 56124 Pisa, Italy.
  • 5. C.N.R. Institute of Clinical Physiology, 56124 Pisa, Italy; Laboratory of Biochemistry, Department of Surgical, Medical, Molecular & Critical Area Pathology, University of Pisa, 56125, Italy.
  • 6. Laboratory of Biochemistry, Department of Surgical, Medical, Molecular & Critical Area Pathology, University of Pisa, 56125, Italy.
  • 7. Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine, University of Gothenburg, 405 30 Gothenburg, Sweden. Electronic address: [email protected].
PMID: 31682799 DOI: 10.1016/j.metabol.2019.153974
Abstract

Mannose is a glucose-associated serum metabolite mainly released by the liver. Recent studies have shown several unexpected pleiotropic effects of mannose including increased regulatory T cells (Tregs), prevention of auto-immune disease and ability to reduce growth of human Cancer cells. We have previously shown in large cohorts that elevated serum mannose levels are associated with future development of Type 2 Diabetes (T2D) and Cardiovascular Disease. However, potential direct effects of mannose on Insulin sensitivity in vivo or in vitro are unknown. We here show that administration of mannose (0.1 g/kg BW twice daily) for one week in man did not elicit negative effects on meal-modified glucose tolerance, markers of inflammation or Insulin levels. Tregs number and Insulin signaling in human liver cells were unchanged. These data suggest that mannose is a marker, and not a mediator, of Insulin Resistance. To verify this, we examined serum mannose levels during long-term euglycemic hyperinsulinemic clamps in non-diabetic and T2D individuals. Mannose was reduced by Insulin infusion in proportion to whole-body Insulin sensitivity. Thus, mannose is a biomarker of Insulin Resistance which may be useful for the early identification of diabetic individuals with Insulin Resistance and increased risk of its complications.