Calcineurin Inhibitors: Pharmacologic Mechanisms Impacting Both Insulin Resistance and Insulin Secretion Leading to Glucose Dysregulation and Diabetes Mellitus.
Calcineurin inhibitors (CNIs), including tacrolimus and cyclosporine, are immune-modulating agents used in autoimmune disorders, glomerulonephritides, and after transplantation. CNIs are implicated as diabetogenic drugs but the mechanism is not clearly elucidated. Calcineurin is a cytosolic-phosphatase critical for T-lymphocyte activation. Calcineurin is widely distributed in different tissues responsible for glucose-regulation including pancreas, liver, skeletal muscle, adipocytes, brain, and gut. We describe the pharmacologic effects of CNIs in different tissues and impact on glucose regulation.
Division of Transplantation, Mayo Clinic, Phoenix, Arizona, USA.
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Chakkera
Division of Endocrinology, Mayo Clinic, Rochester, Minnesota, USA.
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Kudva
Division of Transplantation, Mayo Clinic, Phoenix, Arizona, USA.
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B
Kaplan
D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D016572:Cyclosporine / Q000009:adverse effects / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000139:chemically induced*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D016559:Tacrolimus / Q000009:adverse effects / Q000494:pharmacology
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D007328:Insulin; D016572:Cyclosporine; D019703:Calcineurin; D005947:Glucose; D016559:Tacrolimus