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 language | English (US) |
|---|---|
| Pages (from-to) | 65-71 |
| Number of pages | 7 |
| Journal | Diabetes |
| Volume | 56 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2007 |
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ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
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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 journal › Article
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TY - JOUR
T1 - Human islet amyloid polypeptide oligomers disrupt cell coupling, induce apoptosis, and impair insulin secretion in isolated human islets
AU - Ritzel, Robert A.
AU - Meier, Juris J.
AU - Lin, Chia Yu
AU - Veldhuis, Johannes D
AU - Butler, Peter C.
PY - 2007/1
Y1 - 2007/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33847012626&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33847012626&partnerID=8YFLogxK
U2 - 10.2337/db06-0734
DO - 10.2337/db06-0734
M3 - Article
C2 - 17192466
AN - SCOPUS:33847012626
VL - 56
SP - 65
EP - 71
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 1
ER -