Pancreastatin is an endogenous peptide that regulates glucose homeostasis

Abstract

Pancreastatin (PST) is a regulatory peptide containing 49 amino acids, first isolated from porcine pancreas. Intracellular and extracellular processing of the prohormone Chromogranin A (Chga) results various bioactive peptides of which PST has dysglycemic activity. PST regulates glucose, lipid, and protein metabolism in liver and adipose tissues. It also regulates the secretion of leptin and expression of leptin and uncoupling protein 2 in adipose tissue. In Chga knockout mice, PST induces gluconeogenesis in the liver. PST reduces glucose uptake in mice hepatocytes and adipocytes. In rat hepatocytes, PST induces glycogenolysis and glycolysis and inhibits glycogen synthesis. In rat adipocytes, PST inhibits lactate production and lipogenesis. These metabolic effects are confirmed in humans. In the dual signaling mechanism of PST receptor, mostly PST activates Gαq/11 protein leads to the activation of phospholipase C β3-isoform, therefore increasing cytoplasmic free calcium and stimulating protein kinase C. PST inhibits the cell growth in rat HTC hepatoma cells, mediated by nitric oxide and cyclic GMP production. Elevated levels of PST correlating with catecholamines have been found in gestational diabetes and essential hypertension. Rise in the blood PST level in Type 2 diabetes suggests that PST is a negative regulator of insulin sensitivity and glucose homeostasis.