Effects of metformin on hyperglycemia in an experimental model of tacrolimus- and sirolimus-induced diabetic rats.

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.

• Authors: Jian Jin, Sun Woo Lim, Long Jin, Ji Hyun Yu, Hyun Seon Kim, Byung Ha Chung, Chul Woo Yang
• Journal: The Korean journal of internal medicine (Korean J Intern Med) Vol. 32 Issue 2 Pg. 314-322 (Mar 2017) ISSN: 2005-6648 [Electronic] Korea (South)
• PMID: 27688296 (Publication Type: Journal Article)

Chemical References

• Hypoglycemic Agents
• Immunosuppressive Agents
• Metformin
• Sirolimus
• Tacrolimus

Topics

• Animals
• Diabetes Mellitus, Experimental (chemically induced, drug therapy, physiopathology)
• Humans
• Hypoglycemic Agents (therapeutic use)
• Immunosuppressive Agents (adverse effects)
• Islets of Langerhans (drug effects, physiopathology)
• Kidney Transplantation (adverse effects)
• Metformin (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Sirolimus (adverse effects)
• Tacrolimus (adverse effects)