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