Diabetes-induced changes in mannan-binding lectin levels and complement activation in a mouse model of type 1 diabetes.
Circulating mannan-binding lectin (MBL) levels are elevated in type 1 diabetes. Further, high MBL levels are associated with the development of diabetic nephropathy. In animals, a direct effect of MBL on diabetic kidney changes is observed. We hypothesized that MBL levels and detrimental complement activation increase as a consequence of diabetes. We measured plasma MBL before and 7 weeks after inducing diabetes by streptozotocin. Mice have two MBLs, MBL-A and MBL-C. Diabetes induction led to an increase in MBL-C concentration, whereas no change during the study was found in the control group. The increase in MBL-C was associated with the increasing plasma glucose levels. In accordance with the observed changes in circulating MBL levels, liver expression of Mbl2mRNA (encoding MBL-C) was increased in diabetes. Mbl1expression (encoding MBL-A) did not differ between diabetic and control animals. The estimated half-life of recombinant human MBL was significantly prolonged in mice with diabetes compared with control mice. Complement activation in plasma and glomeruli did not differ between groups. We demonstrate for the first time that MBL levels increase after induction of diabetes and in parallel with increasing plasma glucose. Our findings support the previous clinical observations of increased MBL in type 1 diabetes. This change may be explained by alternations in both MBL production and turnover.
The Medical Research Laboratories, Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus C, Denmark. jakob.oestergaard@dadlnet.dk
J A
JA
Ostergaard
M
M
Bjerre
F
F
Dagnaes-Hansen
T K
TK
Hansen
S
S
Thiel
A
A
Flyvbjerg
D000818:Animals; D001786:Blood Glucose / Q000276:immunology / Q000378:metabolism; D003167:Complement Activation / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics / Q000276:immunology*; D003928:Diabetic Nephropathies / Q000097:blood / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006801:Humans; D007328:Insulin / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D037601:Mannose-Binding Lectin / Q000097:blood / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001786:Blood Glucose; D007328:Insulin; D037601:Mannose-Binding Lectin; D020033:Protein Isoforms