Acute and chronic effects of glucose and carbachol on insulin secretion and phospholipase C activation: studies with diazoxide and atropine
| Autor: | Walter S. Zawalich, Hanae Yamazaki, William M. Philbrick, Kathleen C. Zawalich |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Atropine
Male medicine.medical_specialty Carbachol Physiology Inositol Phosphates Endocrinology Diabetes and Metabolism medicine.medical_treatment In Vitro Techniques Carbohydrate metabolism Rats Sprague-Dawley Islets of Langerhans Physiology (medical) Internal medicine Insulin Secretion Muscarinic acetylcholine receptor Diazoxide medicine Animals Insulin Pancreatic hormone Phospholipase C Chemistry Colforsin Rats Enzyme Activation Glucose Endocrinology Hyperglycemia Type C Phospholipases Inositol medicine.drug |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 290:E26-E33 |
| ISSN: | 1522-1555 0193-1849 |
| DOI: | 10.1152/ajpendo.00149.2005 |
| Popis: | The acute and chronic effects of 20 mM glucose and 10 μM carbachol on β-cell responses were investigated. Acute exposure of rat islets to 20 mM glucose increased glucose usage rates and resulted in a large insulin-secretory response during a dynamic perifusion. The secretory, but not the metabolic, effect of 20 mM glucose was abolished by simultaneous exposure to 100 μM diazoxide. Glucose (20 mM) significantly increased inositol phosphate (IP) accumulation, an index of phospholipase C (PLC) activation, from [3H]inositol-prelabeled islets. Diazoxide, but not atropine, abolished this effect as well. Unlike 20 mM glucose, 10 μM carbachol (in the presence of 5 mM glucose) increased IP accumulation but had no effect on insulin secretion or glucose (5 mM) metabolism. The IP effect was abolished by 50 μM atropine but not by diazoxide. Chronic 3-h exposure of islets to 20 mM glucose or 10 μM carbachol profoundly reduced both the insulin-secretory and PLC responses to a subsequent 20 mM glucose stimulus. The adverse effects of chronic glucose exposure were abolished by diazoxide but not by atropine. In contrast, the adverse effects of carbachol were abolished by atropine but not by diazoxide. Prior 3 h of exposure to 20 mM glucose or carbachol had no inhibitory effect on glucose metabolism. Significant secretory responses could be evoked from 20 mM glucose- or carbachol-pretreated islets by the inclusion of forskolin. These findings support the concept that an early event in the evolution of β-cell desensitization is the impaired activation of islet PLC. |
| Databáze: | OpenAIRE |
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