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

Abstract

Background/AimsMetformin (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).MethodsDM 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.ResultsIPGTT 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.ConclusionsMET has different effects on hyperglycemia caused by TAC and SRL. The discrepancy between these drugs is related to their different mechanisms causing DM.

The Biological Impacts of Sitagliptin on the Pancreas of a Rat Model of Type 2 Diabetes Mellitus: Drug Interactions with Metformin

“…In accordance with literature, the doses of sitagliptin and metformin (10 mg/kg and 200 mg/kg, respectively) were selected from the low end of the ranges used in previous studies [16][17][18], in order that a potential synergistic effect could be detected and to avoid metformin toxicity if given ≥600 mg/kg/day [19]. The dose of medications was adjusted every week, according to the body weight changes to keep a similar dose per kg body weight of rat, over the whole period of treatment, for each group.…”

“…Biology 2020, 9, x FOR PEER REVIEW 4 of 26 mg/kg/day [19]. The dose of medications was adjusted every week, according to the body weight changes to keep a similar dose per kg body weight of rat, over the whole period of treatment, for each group.…”

Ginseng extract reduces tacrolimus-induced oxidative stress by modulating autophagy in pancreatic beta cells

“…3 The pathogenesis of Tac-induced diabetes mellitus (DM) is unclear, but we and others reported that the direct toxic effect of Tac on pancreatic beta cells and oxidative stress has a pivotal role in Tac-induced DM. [4][5][6] Ginseng, a traditional medicine, is commonly used to modulate immune functions and metabolism, and ginsenosides are the pharmacologically active components in ginseng and that are used as traditional medicine to treat various diseases. 7 Korean red ginseng extract (KRGE) is a popular and commercially available health food, but its mechanism is still undetermined.…”

Metformin attenuates streptozotocin-induced diabetic nephropathy in rats through activation of AMPK signaling pathway

“…It improves plasma levels of glucagon-like peptide 1 (GLP-1), peripheral and liver sensitivity to insulin, decreases hepatic glucose production, and causes weight reduction (21). A recent study demonstrated that metformin stimulates the adenosine monophosphate protein kinase signaling pathway (22). Lee et al reported that phosphorylation of AMPK signaling levels is diminished in the diabetesinduced renal hypertrophy (23).…”