Disturbed islet-cell function related to endogenous gastrin release. Studies on insulin secretion and glucose tolerance in pernicious anemia.

Abstract

A B S T R A C T The insulin and gastrin response to oral glucose, intravenous glucose, or a protein-rich meal were measured in 44 nondiabetic patients with pernicious anemia (PA) and in 44 control subjects. 36 of the PApatients had hypergastrinemia, while serum gastrin concentrations in the remaining eight patients were below normal. Three hypergastrinemic PA-patients were in addition studied during an oral glucose loading with synchronous intravenous infusion of gastrin-17.During both oral and intravenous glucose tests blood glucose concentrations were similar in patients and in controls. After ingestion of protein blood glucose concentrations in PA-patients with hypergastrinemia were above those of the controls (P <0.05). Parenteral infusion of gastrin-17 during oral glucose loading also increased blood glucose concentrations above the levels observed after glucose alone. In PA-patients with hypergastrinemia the insulin response was augmented in all tests. In patients with hypogastrinemia serum insulin concentrations were lower than normal in the fasting state and during stimulation with glucose intravenously (P < 0.01). In hypergastrinemic patients serum gastrin concentrations decreased after oral as well as intravenous glucose administration. The decrease was larger during the oral test. In hypogastrinemia oral glucose induced, as in controls, a small initial rise followed by a slow fall in serum gastrin concentrations. No variations were seen in these patients during the intravenous glucose infusion. Gel filtration of serum from hypergastrinemic patients disclosed a decrease in the concentrations of all Dr. Rehfeld's present address is Institute of Medical Biochemistry, University of Aarhus, DK-8000 Aarhus C, Denmark.Received for publication 1 December 1975 and in rezHsed form 16 February 1976. four main components of gastrin during the glucose loadings.Taken together with earlier studies on the effect of exogenous gastrin the results suggest that endogenous hypergastrinemia induces hyperglycemia and potentiates insulin secretion. In contrast hypogastrinemia is associated with hypoinsulinism.

Postprandial Acid Secretion and Serum Gastrin Response before and after Exclusion of the Proximal Small Intestine in Cats

“…Synthetic human gastrin-17 was used also as standard and tracer [22]. Details on assay reliability have been published previously [17,23], Antiserum 2604 binds serum gastrin components 1-IV with al most equimolar potency [14,15]. All gastrin determi nations were carried out in the same assay.…”

Effects of 12 weeks’ treatment with a proton pump inhibitor on insulin secretion, glucose metabolism and markers of cardiovascular risk in patients with type 2 diabetes: a randomised double-blind prospective placebo-controlled study

“…This is in contrast to previous animal and retrospective studies and to human studies using exogenous gastrin in modest doses [6] or endogenous hypergastrinaemia correlating with insulin secretion [7,8]. In one animal study [5], rodents were fed a high-energy diet until they reached a morning blood glucose level >10 mmol/l.…”

“…Similarly, studies on rodents (Psammomys obesus) have shown that gastrin treatment stimulates insulin secretion, thereby reducing the blood glucose levels and increasing beta cell mass [5]. Moreover, studies in man have shown that moderate hypergastrinaemia (exogenous as well as endogenous gastrin source) also increases insulin secretion [6][7][8].…”

Progastrin expression in mammalian pancreas.

“…It is, however, possible that a low level of expression has physiological significance. Hence, the concentration of locally released gastrin may be sufficient to affect the growth of neighboring pancreatic cells, as illustrated by the islet cell hyperplasia (35)(36)(37) and hyperinsulinemia (38) accompanying hypergastrinemia in man. In this context, the complete sulfation of pancreatic gastrin (refs.…”