Korean J Intern Med.
2017 Mar;32(2):314-322. 10.3904/kjim.2015.394.
Effects of metformin on hyperglycemia in an experimental model of tacrolimus- and sirolimus-induced diabetic rats
- Affiliations
-
- 1Transplant Research Center, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea. yangch@catholic.ac.kr
- 2Convergent Research Consortium for Immunologic Disease, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
- 3Division of Nephrology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
- KMID: 2371655
- DOI: http://doi.org/10.3904/kjim.2015.394
Abstract
- BACKGROUND/AIMS
Metformin (MET) is a first-line drug for type 2 diabetes mellitus (DM); its effect on new-onset diabetes after transplantation caused by immunosuppressant therapy is unclear. We compared the effects of MET on DM caused by tacrolimus (TAC) or sirolimus (SRL).
METHODS
DM was induced by injection of TAC (1.5 mg/kg) or SRL (0.3 mg/kg) for 2 weeks in rats, and MET (200 mg/kg) was injected for 2 more weeks. The effects of MET on DM caused by TAC or SRL were evaluated using an intraperitoneal glucose tolerance test (IPGTT) and by measuring plasma insulin concentration, islet size, and glucose-stimulated insulin secretion (GSIS). The effects of MET on the expression of adenosine monophosphate-activated protein kinase (AMPK), a pharmacological target of MET, were compared between TAC- and SRL-treated islets.
RESULTS
IPGTT showed that both TAC and SRL induced hyperglycemia and reduced plasma insulin concentration compared with vehicle. These changes were reversed by addition of MET to SRL but not to TAC. Pancreatic islet cell size was decreased by TAC but not by SRL, but addition of MET did not affect pancreatic islet cell size in either group. MET significantly increased GSIS in SRL- but not in TAC-treated rats. AMPK expression was not affected by TAC but was significantly decreased in SRL-treated islets. Addition of MET restored AMPK expression in SRL-treated islets but not in TAC-treated islets.
CONCLUSIONS
MET has different effects on hyperglycemia caused by TAC and SRL. The discrepancy between these drugs is related to their different mechanisms causing DM.
MeSH Terms
-
Adenosine
AMP-Activated Protein Kinases
Animals
Cell Size
Diabetes Mellitus, Type 2
Glucose Tolerance Test
Hyperglycemia*
Insulin
Islets of Langerhans
Metformin*
Models, Theoretical*
Plasma
Protein Kinases
Rats*
Sirolimus
Tacrolimus
AMP-Activated Protein Kinases
Adenosine
Insulin
Metformin
Protein Kinases
Sirolimus
Tacrolimus
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