Human islet amyloid polypeptide oligomers disrupt cell coupling, induce apoptosis, and impair insulin secretion in isolated human islets

Robert A. Ritzel, Juris J. Meier, Chia Yu Lin, Johannes D Veldhuis, Peter C. Butler

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

Insulin secretion from the 2,000-3,000 β-cells in an islet is a highly synchronized activity with discharge of insulin in coordinate secretory bursts at approximately 4-min intervals. Insulin secretion progressively declines in type 2 diabetes and following islet transplantation. Both are characterized by the presence of islet amyloid derived from islet amyloid polypeptide (IAPP). In the present studies, we examined the action of extracellular human IAPP (h-IAPP) on morphology and function of human islets. Because oligomers of h-IAPP are known to cause membrane disruption, we questioned if application of h-IAPP oligomers to human islets would lead to disruption of islet architecture (specifically cell-to-cell adherence) and a decrease in coordinate function (e.g., increased entropy of insulin secretion and diminished coordinate secretory bursts). Both hypotheses are affirmed, leading to a novel hypothesis for impaired insulin secretion in type 2 diabetes and following islet transplantation, specifically disrupted cell-to-cell adherence in islets through the actions of membrane-disrupting IAPP oligomers.

Original languageEnglish (US)
Pages (from-to)65-71
Number of pages7
JournalDiabetes
Volume56
Issue number1
DOIs
StatePublished - Jan 2007

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Islet Amyloid Polypeptide
Insulin
Apoptosis
Islets of Langerhans Transplantation
Type 2 Diabetes Mellitus
Membranes
Entropy
Islets of Langerhans
Amyloid

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Human islet amyloid polypeptide oligomers disrupt cell coupling, induce apoptosis, and impair insulin secretion in isolated human islets. / Ritzel, Robert A.; Meier, Juris J.; Lin, Chia Yu; Veldhuis, Johannes D; Butler, Peter C.

In: Diabetes, Vol. 56, No. 1, 01.2007, p. 65-71.

Research output: Contribution to journalArticle

Ritzel, Robert A. ; Meier, Juris J. ; Lin, Chia Yu ; Veldhuis, Johannes D ; Butler, Peter C. / Human islet amyloid polypeptide oligomers disrupt cell coupling, induce apoptosis, and impair insulin secretion in isolated human islets. In: Diabetes. 2007 ; Vol. 56, No. 1. pp. 65-71.
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