Diabetes‐induced Changes in Mannan‐binding Lectin Levels and Complement Activation in a Mouse Model of Type 1 Diabetes

Abstract

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.

Increased All-Cause Mortality in Patients With Type 1 Diabetes and High-Expression Mannan-Binding Lectin Genotypes: A 12-Year Follow-up Study

“…The positive correlation between HbA 1c and MBL concentrations in the current study supports that the MBL concentration in humans increases within a given genotype as a consequence of diabetes in agreement with animal studies (14).…”

“…However, MBL concentrations are higher in patients with diabetes than in healthy subjects, despite similar MBL2 genotype distribution (2,6,12,13). Animal studies suggest this to be explained by a secondary increase in MBL concentration after diabetes induction (14). Finally, we recently showed that H-ficolin, another complement-activating pattern-recognition molecule, is also associated with development of diabetic kidney changes (15).…”

Targeting Complement System Mannose Binding Lectin (Mbl) –In Diabetic Nephropathy ?

“…[13] WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES The increase in MBL-Complement was associated with the increasing plasma glucose levels. [1] MBL levels increase after induction of diabetes and in parallel with increasing plasma glucose. [1] Elevated MBL level in T1DM…”

“…[1] MBL levels increase after induction of diabetes and in parallel with increasing plasma glucose. [1] Elevated MBL level in T1DM…”

“…[2] MBL concentrations are significantly elevated in patients with type 1 diabetes and suggest a possible role of MBL in the pathogenesis of renovascular complications in diabetes. [1,2] …”