β-Cell failure in type 2 diabetes: Postulated mechanisms and prospects for prevention and treatment

Philippe A. Halban, Kenneth S. Polonsky, Donald W. Bowden, Meredith A. Hawkins, Charlotte Ling, Kieren J. Mather, Alvin C. Powers, Christopher J. Rhodes, Lori Sussel, Gordon C. Weir

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

OBJECTIVE: This article examines the foundation of β-cell failure in type 2 diabetes (T2D) and suggests areas for future research on the underlying mechanisms that may lead to improved prevention and treatment. RESEARCH DESIGN AND METHODS: A group of experts participated in a conference on 14-16 October 2013 cosponsored by the Endocrine Society and the American Diabetes Association. A writing group prepared this summary and recommendations. RESULTS: The writing group based this article on conference presentations, discussion, and debate. Topics covered include genetic predisposition, foundations of β-cell failure, natural history of β-cell failure, and impact of therapeutic interventions. CONCLUSIONS: β-Cell failure is central to the development and progression of T2D. It antedates and predicts diabetes onset and progression, is in part genetically determined, and often can be identified with accuracy even though current tests are cumbersome and not well standardized. Multiple pathways underlie decreased β-cell function and mass, some of which may be shared and may also be a consequence of processes that initially caused dysfunction. Goals for future research include to 1) impact the natural history of β-cell failure; 2) identify and characterize genetic loci for T2D; 3) target β-cell signaling, metabolic, and genetic pathways to improve function/mass; 4) develop alternative sources of β-cells for cell-based therapy; 5) focus on metabolic environment to provide indirect benefit to β-cells; 6) improve understanding of the physiology of responses to bypass surgery; and 7) identify circulating factors and neuronal circuits underlying the axis of communication between the brain and β-cells.

Original languageEnglish (US)
Pages (from-to)1983-1992
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number6
DOIs
StatePublished - 2014

Fingerprint

Medical problems
Type 2 Diabetes Mellitus
Cell signaling
Physiology
Therapeutics
Surgery
Brain
Natural History
Networks (circuits)
Communication
Genetic Loci
Genetic Predisposition to Disease
Cell- and Tissue-Based Therapy
Metabolic Networks and Pathways
Research Design

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

β-Cell failure in type 2 diabetes : Postulated mechanisms and prospects for prevention and treatment. / Halban, Philippe A.; Polonsky, Kenneth S.; Bowden, Donald W.; Hawkins, Meredith A.; Ling, Charlotte; Mather, Kieren J.; Powers, Alvin C.; Rhodes, Christopher J.; Sussel, Lori; Weir, Gordon C.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 99, No. 6, 2014, p. 1983-1992.

Research output: Contribution to journalArticle

Halban, PA, Polonsky, KS, Bowden, DW, Hawkins, MA, Ling, C, Mather, KJ, Powers, AC, Rhodes, CJ, Sussel, L & Weir, GC 2014, 'β-Cell failure in type 2 diabetes: Postulated mechanisms and prospects for prevention and treatment', Journal of Clinical Endocrinology and Metabolism, vol. 99, no. 6, pp. 1983-1992. https://doi.org/10.1210/jc.2014-1425
Halban, Philippe A. ; Polonsky, Kenneth S. ; Bowden, Donald W. ; Hawkins, Meredith A. ; Ling, Charlotte ; Mather, Kieren J. ; Powers, Alvin C. ; Rhodes, Christopher J. ; Sussel, Lori ; Weir, Gordon C. / β-Cell failure in type 2 diabetes : Postulated mechanisms and prospects for prevention and treatment. In: Journal of Clinical Endocrinology and Metabolism. 2014 ; Vol. 99, No. 6. pp. 1983-1992.
@article{b9e1d6b0cc22409596d80955dbc1fc50,
title = "β-Cell failure in type 2 diabetes: Postulated mechanisms and prospects for prevention and treatment",
abstract = "OBJECTIVE: This article examines the foundation of β-cell failure in type 2 diabetes (T2D) and suggests areas for future research on the underlying mechanisms that may lead to improved prevention and treatment. RESEARCH DESIGN AND METHODS: A group of experts participated in a conference on 14-16 October 2013 cosponsored by the Endocrine Society and the American Diabetes Association. A writing group prepared this summary and recommendations. RESULTS: The writing group based this article on conference presentations, discussion, and debate. Topics covered include genetic predisposition, foundations of β-cell failure, natural history of β-cell failure, and impact of therapeutic interventions. CONCLUSIONS: β-Cell failure is central to the development and progression of T2D. It antedates and predicts diabetes onset and progression, is in part genetically determined, and often can be identified with accuracy even though current tests are cumbersome and not well standardized. Multiple pathways underlie decreased β-cell function and mass, some of which may be shared and may also be a consequence of processes that initially caused dysfunction. Goals for future research include to 1) impact the natural history of β-cell failure; 2) identify and characterize genetic loci for T2D; 3) target β-cell signaling, metabolic, and genetic pathways to improve function/mass; 4) develop alternative sources of β-cells for cell-based therapy; 5) focus on metabolic environment to provide indirect benefit to β-cells; 6) improve understanding of the physiology of responses to bypass surgery; and 7) identify circulating factors and neuronal circuits underlying the axis of communication between the brain and β-cells.",
author = "Halban, {Philippe A.} and Polonsky, {Kenneth S.} and Bowden, {Donald W.} and Hawkins, {Meredith A.} and Charlotte Ling and Mather, {Kieren J.} and Powers, {Alvin C.} and Rhodes, {Christopher J.} and Lori Sussel and Weir, {Gordon C.}",
year = "2014",
doi = "10.1210/jc.2014-1425",
language = "English (US)",
volume = "99",
pages = "1983--1992",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "6",

}

TY - JOUR

T1 - β-Cell failure in type 2 diabetes

T2 - Postulated mechanisms and prospects for prevention and treatment

AU - Halban, Philippe A.

AU - Polonsky, Kenneth S.

AU - Bowden, Donald W.

AU - Hawkins, Meredith A.

AU - Ling, Charlotte

AU - Mather, Kieren J.

AU - Powers, Alvin C.

AU - Rhodes, Christopher J.

AU - Sussel, Lori

AU - Weir, Gordon C.

PY - 2014

Y1 - 2014

N2 - OBJECTIVE: This article examines the foundation of β-cell failure in type 2 diabetes (T2D) and suggests areas for future research on the underlying mechanisms that may lead to improved prevention and treatment. RESEARCH DESIGN AND METHODS: A group of experts participated in a conference on 14-16 October 2013 cosponsored by the Endocrine Society and the American Diabetes Association. A writing group prepared this summary and recommendations. RESULTS: The writing group based this article on conference presentations, discussion, and debate. Topics covered include genetic predisposition, foundations of β-cell failure, natural history of β-cell failure, and impact of therapeutic interventions. CONCLUSIONS: β-Cell failure is central to the development and progression of T2D. It antedates and predicts diabetes onset and progression, is in part genetically determined, and often can be identified with accuracy even though current tests are cumbersome and not well standardized. Multiple pathways underlie decreased β-cell function and mass, some of which may be shared and may also be a consequence of processes that initially caused dysfunction. Goals for future research include to 1) impact the natural history of β-cell failure; 2) identify and characterize genetic loci for T2D; 3) target β-cell signaling, metabolic, and genetic pathways to improve function/mass; 4) develop alternative sources of β-cells for cell-based therapy; 5) focus on metabolic environment to provide indirect benefit to β-cells; 6) improve understanding of the physiology of responses to bypass surgery; and 7) identify circulating factors and neuronal circuits underlying the axis of communication between the brain and β-cells.

AB - OBJECTIVE: This article examines the foundation of β-cell failure in type 2 diabetes (T2D) and suggests areas for future research on the underlying mechanisms that may lead to improved prevention and treatment. RESEARCH DESIGN AND METHODS: A group of experts participated in a conference on 14-16 October 2013 cosponsored by the Endocrine Society and the American Diabetes Association. A writing group prepared this summary and recommendations. RESULTS: The writing group based this article on conference presentations, discussion, and debate. Topics covered include genetic predisposition, foundations of β-cell failure, natural history of β-cell failure, and impact of therapeutic interventions. CONCLUSIONS: β-Cell failure is central to the development and progression of T2D. It antedates and predicts diabetes onset and progression, is in part genetically determined, and often can be identified with accuracy even though current tests are cumbersome and not well standardized. Multiple pathways underlie decreased β-cell function and mass, some of which may be shared and may also be a consequence of processes that initially caused dysfunction. Goals for future research include to 1) impact the natural history of β-cell failure; 2) identify and characterize genetic loci for T2D; 3) target β-cell signaling, metabolic, and genetic pathways to improve function/mass; 4) develop alternative sources of β-cells for cell-based therapy; 5) focus on metabolic environment to provide indirect benefit to β-cells; 6) improve understanding of the physiology of responses to bypass surgery; and 7) identify circulating factors and neuronal circuits underlying the axis of communication between the brain and β-cells.

UR - http://www.scopus.com/inward/record.url?scp=84902352296&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902352296&partnerID=8YFLogxK

U2 - 10.1210/jc.2014-1425

DO - 10.1210/jc.2014-1425

M3 - Article

C2 - 24712577

AN - SCOPUS:84902352296

VL - 99

SP - 1983

EP - 1992

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 6

ER -