Suppressive effect of insulin infusion on chemokines and chemokine receptors.
OBJECTIVE
In view of the previously described anti-inflammatory effects of insulin, we investigated the potential suppressive effect of insulin on plasma concentrations and expression of the chemokines, monocyte chemoattractant protein-1 (MCP-1) and regulated on activation normal T-cell expressed and secreted (RANTES) and their receptors, chemokine receptor (CCR)-2 and CCR-5, in mononuclear cells (MNCs). We also investigated the effect of insulin on other chemokines.


METHODS
Ten obese type 2 diabetic patients were infused with insulin (2 units/h with 100 ml of 5% dextrose/h) for 4 h. Another 8 and 6 type 2 diabetic patients were infused with 100 ml of 5% dextrose/h or saline for 4 h, respectively, and served as control subjects. Blood samples were obtained at 0, 2, 4, and 6 h.


RESULTS
Insulin infusion significantly suppressed the plasma concentrations of MCP-1, eotaxin, and RANTES and the expression of RANTES, macrophage inflammatory protein (MIP)-1beta, CCR-2, and CCR-5 in MNCs at 2 and 4 h. Dextrose and saline infusions did not alter these indexes.


CONCLUSIONS
A low-dose infusion of insulin suppresses the plasma concentration of key chemokines, MCP-1, and RANTES, and the expression of their respective receptors, CCR-2 and CCR-5, in MNCs. Insulin also suppresses the expression of RANTES and MIP-1beta in MNCs. These actions probably contribute to the comprehensive anti-inflammatory effect of insulin.
Ghanim
Husam
H
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, New York, USA. pdandona@kaleidahealth.org
Korzeniewski
Kelly
K
Sia
Chang Ling
CL
Abuaysheh
Sanaa
S
Lohano
Teekam
T
Chaudhuri
Ajay
A
Dandona
Paresh
P
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D054413:Chemokine CCL11 / Q000097:blood / Q000235:genetics; D054407:Chemokine CCL4 / Q000097:blood / Q000235:genetics; D018946:Chemokine CCL5 / Q000097:blood / Q000235:genetics; D054428:Chemokine CX3CL1 / Q000097:blood / Q000235:genetics; D054377:Chemokine CXCL12 / Q000097:blood / Q000235:genetics; D018925:Chemokines / Q000097:blood* / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood; D016209:Interleukin-8 / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000276:immunology; D054390:Receptors, CCR2 / Q000097:blood / Q000235:genetics; D019713:Receptors, CCR5 / Q000097:blood / Q000235:genetics; D019718:Receptors, CXCR4 / Q000097:blood / Q000235:genetics; D019707:Receptors, Chemokine / Q000097:blood* / Q000235:genetics
D001786:Blood Glucose; C515456:CCL11 protein, human; C066507:CCL4 protein, human; C515334:CCR2 protein, human; D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054413:Chemokine CCL11; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054428:Chemokine CX3CL1; D054377:Chemokine CXCL12; D018925:Chemokines; D007004:Hypoglycemic Agents; D007166:Immunosuppressive Agents; D007328:Insulin; D016209:Interleukin-8; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine