Biphasic insulin secretion from freshly isolated or cultured, perifused rodent islets: comparative studies with rats and mice

• Published in: Metabolism, clinical and experimental Vol. 57; no. 1; pp. 30 - 39
• Main Authors: Zawalich, Walter S, Yamazaki, Hanae, Zawalich, Kathleen C
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 2008; Elsevier
• Subjects: Animals; Biological and medical sciences; Cells, Cultured; Endocrinology & Metabolism; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Glucose - pharmacology; Insulin - metabolism; Insulin Secretion; Islets of Langerhans - cytology; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Kinetics; Male; Mice; Perfusion; Rats; Rats, Sprague-Dawley; Species Specificity; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Cell culture; Pancreatic hormone; Rat; Secretion; Langerhans islet; Rodentia; Insulin; Vertebrata; Mammalia; Mouse; Animal; Endocrinology; Comparative study; Endocrine pancreas
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2007.07.020

Abstract In the present report, we compared the insulin secretory responses of freshly isolated, perifused rat and mouse islets to glucose. Prestimulatory glucose levels were changed to assess their influence on the subsequent secretory responses. Additional studies included experiments with the incretin factor glucagon-like peptide-1 (GLP-1), the cholinergic agonist carbachol, and the α 2 agonist epinephrine. Our findings demonstrate that under conditions where glucose (8.5-11.1 mmol/L) evokes a dramatic biphasic insulin secretory response from perifused rat islets, mouse islets exhibit little response. Increasing the prestimulatory glucose level to 8.5 mmol/L dramatically distorts subsequently measured glucose-induced insulin secretion from rat islets but allows the evocation of a modest but clear biphasic response from mouse islets in response to 30 mmol/L, but not 11.1 or 16.7 mmol/L, glucose. In the presence of a minimally effective glucose level (10 mmol/L), mouse islets remain exquisitely sensitive to the combined stimulatory effects of GLP-1 (2.5 nmol/L) plus carbachol (0.5 μ mol/L) and to the inhibitory influence of epinephrine (10 nmol/L). Short-term culture of rat islets in CMRL 1066 containing 5.6 mmol/L glucose resulted in a significant decrease in the secretory response to 11.1 mmol/L glucose, whereas the same manipulation improved mouse islet responses. It is concluded that the process of collagenase isolating islets does not alter mouse islet sensitivity in any adverse way and that increasing the prestimulatory glucose level can indeed alter the pattern of insulin secretion in either a positive or negative manner depending upon the species being investigated. Prior short-term culture of rodent islets differentially affects secretion from these 2 species.