Chick Pancreatic B Islets as an Alternative In Vitro Model for Screening Insulin Secretagogues

Abstract

Previously, we reported a simple technique to isolate functional B islets from chick pancreata with retention of their insulin secretory ability in response to glucose challenge. To test the hypothesis that chick B islets are equally good candidates as mammalian islets for screening hypoglycemics and insulin secretagogues, we compared the structural and functional status of chick B islets with those of normal and diabetic mouse islets. Pancreata from chick, normal (nondiabetic) mice, and diabetic mice were collected, fixed, and processed for histological analysis using Gomori stain to distinguish A and B cells from islets. Similarly isolated islets from these animals were treated with different concentrations of tolbutamide, a known insulin secretagogue, and glucose to study insulin release. Histological analysis of pancreata from chicks and normal mice revealed intact B cells, whereas those from diabetic mice were destroyed. The insulin secretory response of chick B islets against the tolbutamide and glucose challenge was comparable to that of normal mouse islets. However, diabetic mouse islets did not respond to glucose challenge, indicating impaired functionality. We have identified a critical window that lies within 5 to 6 d posthatching for isolating chick B islets showing maximum glucose responsiveness and insulin secretion. The previous reports on chicken pancreatic islets involve the use of 4- to 6-wk-old chicks in which islets were found to be nonresponsive to glucose and, hence, could not be used for testing insulin secretory activity. However, our data on B islets from 5- to 6-d-old chick pancreata is highly promising, as islets are responsive to insulin secretagogues. The present data thus indicates that chick B islets can be used as an alternative in vitro model for screening insulin secretagogue and hypoglycemics.