Mechanism of FK506-induced glucose intolerance in rats.

Hirano, Yuri; Mitamura, Takashi; Tamura, Takayuki; Ohara, Kaname; Mine, Yasuhiro; Noguchi, Hideyo

doi:10.2131/jts.19.2_61

Cited by 20 publications

(12 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, tacrolimus may also affect both beta-cell function and peripheral insulin resistance. Several studies have demonstrated that tacroli-mus inhibits insulin secretion from the beta-cell [19,20,21,22,23]. Following a 2-week treatment course, tacrolimus reversibly suppressed insulin gene transcription in normal rats [23].…”

Section: Discussionmentioning

confidence: 99%

Increased incidence in post-transplant diabetes mellitus in children: a case-control analysis

Greenspan

Gitelman

Leung

et al. 2002

Pediatric Nephrology

View full text Add to dashboard Cite

There is limited information regarding the incidence and features of post-transplant diabetes mellitus (PTDM) in pediatric renal transplant recipients. We noted a recent increased frequency of PTDM and reviewed charts of children who underwent renal transplantation from 1 September 1986 to 31 August 1999 to characterize the risk factors and natural history of PTDM. Sixteen children were identified with PTDM, and were each matched with two transplanted controls who did not develop PTDM. Clinical presentation varied from asymptomatic hyperglycemia to hyperosmolar dehydration or diabetic ketoacidosis. The mean time from transplantation to PTDM presentation was 1.2 years (range 1 day to 6.2 years). Significant risk factors for PTDM included: first degree family history of type 2 DM [odds ratio (OR) 23.9]; second degree family history of type 2 DM (OR 5.8); tacrolimus use (OR 9.1 versus cyclosporin); and hyperglycemia in the 2 weeks immediately after transplantation (OR 4.7). Seven of eight children with persistent PTDM continue to receive insulin. Patients with persistent PTDM had later onset disease (mean 1.9 years) compared to those with transient PTDM (0.3 years), suggesting different pathophysiologic processes. We suggest that all children undergoing renal transplantation be screened routinely for PTDM after transplantation, and that such patients may benefit from the avoidance of tacrolimus, as it may cause permanent beta-cell injury.

show abstract

Section: Discussionmentioning

confidence: 99%

Increased incidence in post-transplant diabetes mellitus in children: a case-control analysis

Greenspan

Gitelman

Leung

et al. 2002

Pediatric Nephrology

View full text Add to dashboard Cite

show abstract

“…One of the most important factors determining the incidence of PTDM is the immunosuppressive regimen (6–8). Almost all patients are treated with similar steroid‐based maintenance immunosuppression.…”

Section: Introductionmentioning

confidence: 99%

Incidence and Cost of New Onset Diabetes Mellitus Among U.S. Wait-Listed and Transplanted Renal Allograft Recipients

Woodward

Schnitzler²,

Baty³

et al. 2003

American Journal of Transplantation

375

285

View full text Add to dashboard Cite

This study sought to determine 1) the incidence and costs of new onset diabetes mellitus (NODM) associated with maintenance immunosuppression regimens following renal transplantation and 2) whether the mode of dialysis pretransplant or the type of calcineurin inhibition used for maintenance immunosuppression affected either the incidence or cost of NODM. The study examined the United States Renal Data System's clinical and financial records from 1994 to 1998 of all adult, first, single-organ, renal transplantations in either 1996 or 1997 with adequate financial records. It used the second diagnosis of diabetes in previously nondiabetic patients to identify NODM. While NODM had an incidence of approximately 6% per year among waitlisted dialysis patients, NODM over the first 2 years post-transplant had an incidence of almost 18% and 30% among patients receiving cyclosporine and tacrolimus, respectively. By 2 years post-transplant, Medicare paid an extra $21 500 per newly diabetic patient. We estimated the cost of diabetes attributable to maintenance immunosuppression regimens to be $2025 and $3308 for each tacrolimus patient and $1137 and $1611 for each cyclosporine patient at 1 and 2 years post-transplant, respectively.

show abstract

“…It has been known for years that chronic treatment with anti‐calcineurinic immunosuppressants of organ‐transplanted patients secondarily induces a diabetic state of a relatively high prevalence which varies according to the study (1–3). In vivo treatment of different animal species with oral doses of tacrolimus of at least 1 mg/kg/day induced glucose intolerance after 2 weeks but no hyperglycemia (4–10). The glucose‐intolerant animals showed a decreased pancreatic insulin content (5), vacuolation and degranulation of the isolated islets (4), an increased rate of islet apoptosis (10) or a decreased immunostaining of insulin, together with a diminished in situ hybridization of insulin mRNA in β‐cells (9).…”

Section: Introductionmentioning

confidence: 99%

Tacrolimus‐Induced Diabetes in Rats Courses with Suppressed Insulin Gene Expression in Pancreatic Islets

Hernández-Fisac

Pizarro-Delgado

Calle

et al. 2007

American Journal of Transplantation

View full text Add to dashboard Cite

An animal model of post-transplant diabetes was induced in rats by treating them daily with 0.1 mg/kg body weight of tacrolimus (FK506) in two i.p. injections. Rats developed hyperglycaemia and glucose intolerance after 9 days of treatment. Pancreatic islets, isolated from treated rats on different days, showed a decreased capacity to secrete insulin in response to 20 mM glucose at days 7 and 14. This suppression of insulin secretion was preceded by a reduction of the islet insulin content on day 5 that was progressively decreasing until the end of the treatment (day 14). Islet content of insulin mRNAs, transcribed from rat insulin genes 1 and 2, was strongly suppressed, similar to the insulin content, at days 7 and 14. Islet mass was not strikingly modified by tacrolimus treatment: the DNA content was slightly decreased at the end (day 14) and the rate of islet cell apoptosis slightly increased. Tacrolimus-induced diabetes in the rat seems to be mainly provoked by a decreased insulin gene transcription with little or no alteration of islet mass. This explains that the observed suppression of all the islet and animal parameters studied was completely reversed 2 weeks after interrupting tacrolimus treatment.

show abstract

Mechanism of FK506-induced glucose intolerance in rats.

Cited by 20 publications

References 15 publications

Increased incidence in post-transplant diabetes mellitus in children: a case-control analysis

Increased incidence in post-transplant diabetes mellitus in children: a case-control analysis

Incidence and Cost of New Onset Diabetes Mellitus Among U.S. Wait-Listed and Transplanted Renal Allograft Recipients

Tacrolimus‐Induced Diabetes in Rats Courses with Suppressed Insulin Gene Expression in Pancreatic Islets

Contact Info

Product

Resources

About