2. Academic Validation
  3. Mannose is an insulin-regulated metabolite reflecting whole-body insulin sensitivity in man

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

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.

Figures