Long-term metabolic and hormonal effects of exenatide on islet transplant recipients with allograft dysfunction

Raquel N. Faradji, Tatiana Froud, Shari Messinger, Kathy Monroy, Antonello Pileggi, Davide Mineo, Thipaporn Tharavanij, Armando J Mendez, Camillo Ricordi, Rodolfo Alejandro

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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 O-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.

Original languageEnglish
Pages (from-to)1247-1259
Number of pages13
JournalCell Transplantation
Volume18
Issue number10-11
DOIs
StatePublished - Dec 1 2009

Fingerprint

Transplants
Insulin
Allografts
Glucose
Grafts
Glucagon
Islet Amyloid Polypeptide
Proinsulin
Peptides
C-Peptide
Hyperglycemia
Transplantation (surgical)
exenatide
Transplant Recipients
Medical problems
Islets of Langerhans Transplantation
Glucagon-Like Peptide 1
Type 1 Diabetes Mellitus
Meals
Regeneration

Keywords

  • Diabetes
  • Exenatide
  • Glucagon
  • Graft dysfunction
  • Insulin
  • Insulin independence
  • Islet
  • Islet transplantation
  • Metabolism

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

Cite this

Long-term metabolic and hormonal effects of exenatide on islet transplant recipients with allograft dysfunction. / Faradji, Raquel N.; Froud, Tatiana; Messinger, Shari; Monroy, Kathy; Pileggi, Antonello; Mineo, Davide; Tharavanij, Thipaporn; Mendez, Armando J; Ricordi, Camillo; Alejandro, Rodolfo.

In: Cell Transplantation, Vol. 18, No. 10-11, 01.12.2009, p. 1247-1259.

Research output: Contribution to journalArticle

Faradji, Raquel N. ; Froud, Tatiana ; Messinger, Shari ; Monroy, Kathy ; Pileggi, Antonello ; Mineo, Davide ; Tharavanij, Thipaporn ; Mendez, Armando J ; Ricordi, Camillo ; Alejandro, Rodolfo. / Long-term metabolic and hormonal effects of exenatide on islet transplant recipients with allograft dysfunction. In: Cell Transplantation. 2009 ; Vol. 18, No. 10-11. pp. 1247-1259.
@article{f6d2c304da8f4bd89627bcf3d2011551,
title = "Long-term metabolic and hormonal effects of exenatide on islet transplant recipients with allograft dysfunction",
abstract = "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 O-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.",
keywords = "Diabetes, Exenatide, Glucagon, Graft dysfunction, Insulin, Insulin independence, Islet, Islet transplantation, Metabolism",
author = "Faradji, {Raquel N.} and Tatiana Froud and Shari Messinger and Kathy Monroy and Antonello Pileggi and Davide Mineo and Thipaporn Tharavanij and Mendez, {Armando J} and Camillo Ricordi and Rodolfo Alejandro",
year = "2009",
month = "12",
day = "1",
doi = "10.3727/096368909X474456",
language = "English",
volume = "18",
pages = "1247--1259",
journal = "Cell Transplantation",
issn = "0963-6897",
publisher = "Cognizant Communication Corporation",
number = "10-11",

}

TY - JOUR

T1 - Long-term metabolic and hormonal effects of exenatide on islet transplant recipients with allograft dysfunction

AU - Faradji, Raquel N.

AU - Froud, Tatiana

AU - Messinger, Shari

AU - Monroy, Kathy

AU - Pileggi, Antonello

AU - Mineo, Davide

AU - Tharavanij, Thipaporn

AU - Mendez, Armando J

AU - Ricordi, Camillo

AU - Alejandro, Rodolfo

PY - 2009/12/1

Y1 - 2009/12/1

N2 - 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 O-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.

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 O-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.

KW - Diabetes

KW - Exenatide

KW - Glucagon

KW - Graft dysfunction

KW - Insulin

KW - Insulin independence

KW - Islet

KW - Islet transplantation

KW - Metabolism

UR - http://www.scopus.com/inward/record.url?scp=75149167570&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=75149167570&partnerID=8YFLogxK

U2 - 10.3727/096368909X474456

DO - 10.3727/096368909X474456

M3 - Article

C2 - 20003758

AN - SCOPUS:75149167570

VL - 18

SP - 1247

EP - 1259

JO - Cell Transplantation

JF - Cell Transplantation

SN - 0963-6897

IS - 10-11

ER -