Elevated Basal Insulin Secretion in Type 2 Diabetes Caused by Reduced Plasma Membrane Cholesterol
Autor: | Enming Zhang, Erik Renström, Thomas Reinbothe, Clemens Lewold, Pawel Buda, Satadal Barik, Johan Helgeson, Vini Nagaraj, Abdulla S. Kazim, Stefan Wennmalm |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Male medicine.medical_specialty endocrine system medicine.medical_treatment Type 2 diabetes Carbohydrate metabolism Biology Exocytosis Diabetes Mellitus Experimental 03 medical and health sciences Islets of Langerhans Endocrinology Membrane Microdomains Internal medicine Diabetes mellitus medicine Animals Insulin Secretion Rats Wistar Molecular Biology Lipid raft Original Research Cell Membrane General Medicine medicine.disease Insulin oscillation Rats 030104 developmental biology Cholesterol Glucose Diabetes Mellitus Type 2 Calcium Female Calcium Channels Oxidation-Reduction |
Zdroj: | Molecular Endocrinology |
ISSN: | 1944-9917 0888-8809 |
Popis: | Elevated basal insulin secretion under fasting conditions together with insufficient stimulated insulin release is an important hallmark of type 2 diabetes, but the mechanisms controlling basal insulin secretion remain unclear. Membrane rafts exist in pancreatic islet cells and spatially organize membrane ion channels and proteins controlling exocytosis, which may contribute to the regulation of insulin secretion. Membrane rafts (cholesterol and sphingolipid containing microdomains) were dramatically reduced in human type 2 diabetic and diabetic Goto-Kakizaki (GK) rat islets when compared with healthy islets. Oxidation of membrane cholesterol markedly reduced microdomain staining intensity in healthy human islets, but was without effect in type 2 diabetic islets. Intriguingly, oxidation of cholesterol affected glucose-stimulated insulin secretion only modestly, whereas basal insulin release was elevated. This was accompanied by increased intracellular Ca2+ spike frequency and Ca2+ influx and explained by enhanced single Ca2+ channel activity. These results suggest that the reduced presence of membrane rafts could contribute to the elevated basal insulin secretion seen in type 2 diabetes. |
Databáze: | OpenAIRE |
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