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

Journal article
Authors E. Ferrannini
Maria Bokarewa
Petra Brembeck
Ritesh Baboota
Shahram Hedjazifar
Kerstin Andersson
S. Baldi
B. Campi
E. Muscelli
A. Saba
Sofia Sterner Isaksson
Caroline Wasén
Ulf Smith
Published in Metabolism: Clinical and Experimental
Volume 102
ISSN 0026-0495
Publication year 2020
Published at Institute of Medicine, Department of Rheumatology and Inflammation Research
Institute of Medicine, Department of Molecular and Clinical Medicine
Language en
Subject categories Endocrinology and Diabetes


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. © 2019 Elsevier Inc.

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