title: Tacrolimus Induces Insulin Resistance and Increases the Glucose Absorption in the Jejunum: A Potential Mechanism of the Diabetogenic Effects.
abstract: BACKGROUND
  The use of the immunosuppressive drug tacrolimus (TAC) is related to new onset diabetes after transplantation. Herein, we examined the effect of intraperitoneal administered TAC on intestinal glucose absorption in mice.
  
  
  METHODS
  Animals received low, medium, or high dose TAC (0.5, 1, or 5 mg/kg/d, respectively), or 0.9% saline solution (control) for 14 days. Oral glucose tolerance test (OGTT), insulin concentration test, and serum TAC concentration measurements was performed after 14 days of TAC exposure. Plasma insulin was assessed and electrogenic glucose absorption were measured by the sodium-dependent increase of the short-circuit current. Expression levels of the glucose transporters sodium glucose co-transporter (SGLT) 1, glucose transporter (GLUT) 2, and GLUT5 were also determined.
  
  
  RESULTS
  Oral glucose absorption assessed by OGTT was significantly enhanced in the low, medium, and high groups. Serum insulin was elevated in the medium and high group compared with the control. Moreover, glucose-induced Isc was significantly higher in TAC administrated groups, which indicates that SGLT1 activity increased. Transcription levels and protein abundance of SGLT1 in the experimental groups also increased compared with the control.
  
  
  CONCLUSIONS
  TAC induced insulin resistance and strengthened intestinal glucose absorption by increasing the activity and expression of the glucose transporter, SGLT1.
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Sun
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: He
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Penghong
authors.initials: P
authors.lastname: Song
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Yan
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007408:Intestinal Absorption / Q000187:drug effects*; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D016559:Tacrolimus / Q000097:blood / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D051246:Glucose Transport Proteins, Facilitative; D007328:Insulin; D005947:Glucose; D016559:Tacrolimus