ABSTRACT
PTP1B has been most consistently shown to act as a negative regulator of insulin action, and animal studies have confirmed that PTP1B plays a key role in glucose homeostasis and energy expenditure. Evidence has also shown that LAR can have a negative impact on cellular insulin signaling, although its exact physiological role has been more difficult to discern from the knock-out and transgenic models. In contrast, SHP-2 positively influences post-insulin receptor signaling on mitogenic pathways in cellular studies, and animal models have confirmed that SHP-2 has important effects on embryonic development as well as a contribution to glucose metabolism. Studies on reduced LRP expression in cellular systems show that this homolog is less likely to play an important role in insulin signaling. These recent studies have provided insight into the physiological role of specific PTPases in insulin action and have provided further evidence for PTP1B, in particular, as a key target for pharmaceutical intervention to enhance insulin action in type 2 diabetes and other insulin-resistant disease states.
PTPASES AND THE REGULATION OF CELLULAR INSULIN ACTION
