ABSTRACT
In the mid-1970s one of us (JFD) began studying the increased protein degradation in liver of rats made acutely diabetic with the drug streptozotocin.3,4 These animals were hyperglyce mic and ketotic, and they died in 3-4 days unless repeatedly injected with insulin. This infor mation is important because less severe insulin deficiency may elicit an opposite response in protein degradation; animals may adapt by decreasing protein degradation in many tissues.5 The increased protein degradation in severe insulin deficiency applied most dramatically to those proteins that were normally very long-lived suggesting that the enhanced degradation was selective for particular substrate proteins to some degree.6 The longer-lived cytosolic pro teins tended to be small,7 basic,8 nonglycosylated9 and/or hydrophilic. 0 These classes of pro teins are synthesized at the same rates during insulin deficiency, so their increased degradation leads to a decline in their intracellular concentration in response to insulin withdrawal.6