Pancreastatin inhibits insulin action in rat adipocytes

Pancreastatin (PST), a regulatory peptide with a general inhibitory effect on secretion, is derived from chromogranin A, a glycoprotein present throug hout the neuroendocrine system. We have previously demonstrated the counter regulatory role of PST on insulin action in rat hepatocytes. Here, we are r eporting the PST effects on rat adipocytes. PST dose dependently inhibits b asal and insulin-stimulated glucose transport, lactate production, and lipo genesis, impairing the main metabolic actions of insulin in adipocytes. The se effects were observed in a wide range of insulin concentrations, leading to a shift to the right in the dose-response curve. Maximal effect was obs erved at 10 nM PST, and the IC50 value was similar to 1 nM. Moreover, PST h as a lipolytic effect in rat adipocytes (ED50 0.1 nM), although it was comp letely inhibited by insulin. In contrast, PST dose dependently stimulated p rotein synthesis and enhanced insulin-stimulated protein synthesis. In summ ary, these data show the lipokinetic effect of PST and the inhibitory effec t of PST on insulin metabolic action within a range of physiological concen trations. Therefore, these results give new pathophysiological basis for th e association of PST with insulin resistance.