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• W2018584626 abstract "Plasma insulin displays 5–10 min oscillations. In Type 2 diabetes the regularity of the oscillations disappears, which may lead to insulin receptor down-regulation and glucose intolerance and explain why pulsatile delivery of the hormone has a greater hypoglycemic effect than continuous delivery. The rhythm is intrinsic to the islet. Variations in metabolism, cytoplasmic Ca2+ concentration ([Ca2+]i), other hormones, neuronal signaling and possibly β-cell insulin receptor expression have been implicated in the regulation of plasma insulin oscillations. Most of these factors are important for amplitude-regulation of the insulin pulses. Although evidence exists supporting a role of both metabolism and [Ca2+]i as pacemakers of the pulses, metabolic oscillations probably have a primary role and [Ca2+]i oscillations a permissive role. Results from islets from animal models of diabetes suggest that altered plasma insulin pattern could be due to lowering of pulse amplitude of insulin oscillations rather than alterations in their frequency. Supporting a role of metabolism, altered plasma insulin oscillations were found in MODY2, MIDD and glycogenosis Type VII, which are linked to alterations in glucokinase, mitochondrial tRNALeu(UUR) and phosphofructokinase. Plasma insulin oscillations require coordination of islet secretory activities in the pancreas. The intrapancreatic ganglia have been suggested as coordinators. The diabetes-associated neuropathy may contribute to the deranged pattern as indicated by glucose intolerance in chagasic patients. Continued investigation of the role and regulation of pulsatile insulin release will lead to better understanding of the pathophysiology of impaired pulsatile insulin release, which could lead to new approaches to restore normal plasma insulin oscillations in diabetes and related diseases. Copyright © 2000 John Wiley & Sons, Ltd." @default.
• W2018584626 created "2016-06-24" @default.
• W2018584626 creator A5089532594 @default.
• W2018584626 date "2000-01-01" @default.
• W2018584626 modified "2023-10-16" @default.
• W2018584626 title "Pathophysiology of impaired pulsatile insulin release" @default.
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