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Suppression of apolipoprotein M expression and secretion in alloxan-diabetic mouse: Partial reversal by insulin
Ning Xu1, Peter Nilsson-Ehle, Bo Ahrén
1Division of Clinical Chemistry and Pharmacology, Institute of Laboratory Medicine, Lund University, Lund, S-221 85 Lund, Sweden. ning.xu@med.lu.se
Abstract:
We previously reported that apolipoprotein M (apoM) expression is reduced in ob/ob mice. Whether such a reduction is specific for this model or is a more general phenomenon in diabetes models is not known. In the present study, we therefore investigated apoM expression and secretion in NMRI mice rendered diabetes through administration of alloxan (120 mg/kg). Plasma glucose levels were markedly increased and plasma insulin levels markedly reduced at 3 days after alloxan. At the same time, that plasma apoM concentrations were decreased by 70%, apoM mRNA levels in liver was decreased by 40%, and apoM mRNA in kidney was decreased by 20% in alloxan-treated mice compared to saline-injected controls. Furthermore we found also that daily sc administration of insulin (5 IU/kg per day) increased plasma apoM levels, and apoM mRNA levels in liver and kidney. We therefore conclude that apoM is reduced in this diabetes model and that exogenous insulin administrations partially reverses the abnormal apoM expression. Based on these results, we suggest that insulin regulates apoM synthesis in vivo and, therefore, that the reduction of apoM expression is a general phenomenon in diabetes models.
Insights
Apolipoprotein M (apoM) levels and gene expression decrease in a mouse model of diabetes. Insulin therapy partially restored apoM levels, suggesting insulin regulates apoM synthesis in vivo.
Area of Science:
- Biochemistry
- Endocrinology
- Metabolic Research
Background:
- Apolipoprotein M (apoM) expression was previously found to be reduced in ob/ob mice.
- The specificity of this reduction in other diabetes models was unknown.
Purpose of the Study:
- To investigate apolipoprotein M (apoM) expression and secretion in a new diabetes model.
- To determine if insulin regulates apoM synthesis in vivo.
Main Methods:
- NMRI mice were induced into diabetes using alloxan (120 mg/kg).
- Plasma glucose, insulin, and apoM concentrations were measured.
- ApoM mRNA levels in the liver and kidney were quantified.
- The effect of daily insulin administration on apoM levels was assessed.
Main Results:
- Alloxan treatment significantly increased plasma glucose and decreased plasma insulin.
- Plasma apoM concentrations decreased by 70% in diabetic mice.
- ApoM mRNA levels were reduced by 40% in the liver and 20% in the kidney.
- Exogenous insulin administration partially reversed the reduction in plasma apoM and hepatic/renal apoM mRNA.
Conclusions:
- Apolipoprotein M (apoM) expression is reduced in the alloxan-induced diabetes model.
- Insulin administration partially reverses abnormal apoM expression, indicating insulin regulates apoM synthesis in vivo.
- The reduction of apoM expression appears to be a general phenomenon in diabetes models.
