Sulfated gastrin stimulates ghrelin and growth hormone release but inhibits insulin secretion in cattle

Abstract

This study was designed to determine the effects of gastrin on the circulating levels of ghrelin, growth hormone (GH), insulin, glucagon and glucose in ruminants. Two experiments were done in eight Holstein steers. Animals were randomly assigned to receive intravenous bolus injections: (1) 0.1% bovine serum albumin in saline as vehicle, 0.8, 4.0 and 20.0μg/kg body weight (BW) of bovine sulfated gastrin-34; (2) vehicle, 0.53μg/kg BW of bovine sulfated gastrin-17 alone or combined with 20.0μg/kg BW of [d-Lys3]-GHRP-6, the selective antagonist of GHS-R1a. Blood samples were collected from −10 to 150min relative to injection time. Concentrations of acyl and total ghrelin in response to gastrin-34 injection were significantly increased in a dose-dependent manner. Concentrations of GH were also markedly elevated by gastrin-34 injection; however, the effect of 20.0μg/kg was weaker than that of 4.0μg/kg. The three doses of gastrin-34 equally decreased insulin levels within 15min and maintained the level until the time of last sampling. Gastrin-34 had no effect (P>0.05) on the levels of glucagon and glucose. Levels of acyl ghrelin increased after administration of gastrin-17 alone or combined with [d-Lys3]-GHRP-6; however, [d-Lys3]-GHRP-6 did not block the elevation of GH by gastrin-17. The present results indicate that sulfated gastrin stimulates both ghrelin and GH release, but the GHS-R1a may not contribute to the release of GH by gastrin. Moreover, sulfated gastrin seems to indirectly maintain the homeostasis of blood glucose through the down-regulation of insulin in ruminants.