Islet morphology in young, genetically diabetic Chinese hamsters during the hyperinsulinemic phase

Plasma glucose and insulin levels were measured in genetically diabetic (subline L) hamsters from 2 1/2 weeks to over 1 year of age. This nonobese subline is known for subnormal pancreatic insulin release. Hyperglycemia was seen from 4 weeks onward. A short period of hyperinsulinemia was seen at 6 weeks of age, after which plasma insulin levels were not different from normal. During the hyperinsulinemia phase (age 6 weeks), pancreatic insulin content was subnormal, islet volume (as percent of pancreas cross-sectional area) and islet size (as islet cross-sectional area in micron2) were not different from normal, islet morphology appeared normal in electron micrographs, but granule volume was slightly but significantly below normal. Because the islets appeared morphologically normal, except for the slight degranulation during the hyperinsulinemic phase, these data suggest (a) that the islets "hypersecrete" to reduce hyperglycemia; but (b) synthesis does not increase enough to maintain a normal pancreatic insulin content; (c) that the first sign of pancreatic failure may be degranulation and decreased insulin synthesis or content; (d) that early peripheral resistance to insulin, rather than early islet failure, may cause the early hyperglycemia, and (e) that early hyperglycemia or insulin resistance contributes to the later islet exhaustion, which is seen in these diabetic animals when adult.