PMID- 20003758
OWN - NLM
STAT- MEDLINE
DCOM- 20100413
LR  - 20181217
IS  - 1555-3892 (Electronic)
IS  - 0963-6897 (Linking)
VI  - 18
IP  - 10
DP  - 2009
TI  - Long-term metabolic and hormonal effects of exenatide on islet transplant 
      recipients with allograft dysfunction.
PG  - 1247-59
LID - 10.3727/096368909X474456 [doi]
AB  - The initial success of islet transplantation (ITx) is followed by graft 
      dysfunction (GDF) and insulin reintroduction. Exenatide, a GLP-1 agonist, 
      increases insulin and decreases glucagon secretion and has potential for 
      beta-cell regeneration. To improve functional islet mass, exenatide treatment was 
      given to ITx recipients with GDF. The objective of this study was to assess 
      metabolic and hormonal effects of exenatide in GDF. In this prospective, 
      single-arm, nonrandomized study, 11 type 1 diabetes recipients of ITx with GDF 
      had HbA1c, weight, insulin requirements, and 5-h mixed meal tolerance test (MMTT; 
      with/without exenatide given before test) at baseline, 3, 6, and 12 months after 
      initiating exenatide treatment. Baseline MMTT showed postprandial hyperglycemia 
      and hyperglucagonemia. Daily exenatide treatment resulted in improved glucose, 
      increased amylin/insulin ratio, and decreased proinsulin/insulin ratio as 
      assessed by MMTT. Glucagon responses remained unchanged. Exenatide administration 
      1 h before MMTT showed decreased glucagon and glucose at 0 min and attenuation in 
      their postprandial rise. Time-to-peak glucose was delayed, followed by insulin, 
      proinsulin, amylin, and C-peptide, indicating glucose-driven insulin secretion. 
      Five subjects completed 12-month follow-up. Glucose and glucagon suppression 
      responses after MMTT with exenatide were no longer observed. Retrospective 
      3-month analysis of these subjects revealed higher and sustained glucagon levels 
      that did not suppress as profoundly with exenatide administration, associated 
      with higher glucose levels and increased C-peptide responses. In conclusion, 
      Exenatide suppresses the abnormal postprandial hyperglucagonemia and 
      hyperglycemia observed in GDF. Changes in amylin and proinsulin secretion may 
      reflect more efficient insulin processing. Different degrees of responsiveness to 
      exenatide were identified. These may help guide the clinical management of ITx 
      recipients.
FAU - Faradji, Raquel N
AU  - Faradji RN
AD  - Clinical Islet Transplant Program, Diabetes Research Institute, University of 
      Miami Leonard M Miller School of Medicine, Miami, FL 33136, USA.
FAU - Froud, Tatiana
AU  - Froud T
FAU - Messinger, Shari
AU  - Messinger S
FAU - Monroy, Kathy
AU  - Monroy K
FAU - Pileggi, Antonello
AU  - Pileggi A
FAU - Mineo, Davide
AU  - Mineo D
FAU - Tharavanij, Thipaporn
AU  - Tharavanij T
FAU - Mendez, Armando J
AU  - Mendez AJ
FAU - Ricordi, Camillo
AU  - Ricordi C
FAU - Alejandro, Rodolfo
AU  - Alejandro R
LA  - eng
SI  - ClinicalTrials.gov/NCT00306098
SI  - ClinicalTrials.gov/NCT00315588
GR  - GCRC-M01RR16587/RR/NCRR NIH HHS/United States
GR  - R01-DK25802/DK/NIDDK NIH HHS/United States
GR  - R01-DK55347/DK/NIDDK NIH HHS/United States
GR  - U42-RR16603/RR/NCRR NIH HHS/United States
PT  - Controlled Clinical Trial
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Transplant
JT  - Cell transplantation
JID - 9208854
RN  - 0 (Amyloid)
RN  - 0 (C-Peptide)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Islet Amyloid Polypeptide)
RN  - 0 (Peptides)
RN  - 0 (Venoms)
RN  - 9007-92-5 (Glucagon)
RN  - 9P1872D4OL (Exenatide)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adult
MH  - Amyloid/metabolism
MH  - Area Under Curve
MH  - C-Peptide/metabolism
MH  - Demography
MH  - Diabetes Mellitus, Type 1/therapy
MH  - Exenatide
MH  - Female
MH  - Glucagon/metabolism
MH  - Glucose/metabolism
MH  - Humans
MH  - Hyperglycemia/etiology
MH  - Hypoglycemic Agents/*pharmacology
MH  - Insulin/metabolism
MH  - Insulin Secretion
MH  - Islet Amyloid Polypeptide
MH  - Islets of Langerhans/metabolism
MH  - *Islets of Langerhans Transplantation
MH  - Male
MH  - Middle Aged
MH  - Peptides/*pharmacology
MH  - Primary Graft Dysfunction/*drug therapy
MH  - Prospective Studies
MH  - Transplantation, Homologous
MH  - Venoms/*pharmacology
EDAT- 2009/12/17 06:00
MHDA- 2010/04/14 06:00
CRDT- 2009/12/17 06:00
PHST- 2009/12/17 06:00 [entrez]
PHST- 2009/12/17 06:00 [pubmed]
PHST- 2010/04/14 06:00 [medline]
AID - ct1967faradji [pii]
AID - 10.3727/096368909X474456 [doi]
PST - ppublish
SO  - Cell Transplant. 2009;18(10):1247-59. doi: 10.3727/096368909X474456.