H. Sankaran

Insulin receptors in isolated mouse pancreatic acini

Abstract Specific insulin receptors were measured in isolated mouse pancreatic acini. Scatchard analyses revealed a high affinity binding site with a K d of 1.67 nM and a lower affinity site with a K d of 83 nM. Binding of insulin to these receptors was rapid, one-half maximal binding occurring at 2 min and maximal binding at 30 min. Insulin stimulated the uptake of the glucose analogue 2-deoxy-D-glucose; maximum effects were detected at 1.67 μM. Insulin, in contrast, had no direct effects on alpha-aminoisobutyric acid uptake. The finding of high affinity insulin receptors in pancreatic acinar cells supports the hypothesis that insulin may directly regulate specific functions in the exocrine pancreas.

CCK4 contains the full hormonal information of cholecystokinin in isolated pancreatic acini

Abstract In mouse and rat isolated pancreatic acini, the C-terminal tetrapeptide amide of CCK (CCK4) fully mimicked the actions of the physiological octapeptide hormone (CCK8) although CCK4 was 10–100 thousand fold less potent than CCK8. Parallelism was observed for stimulation of both amylase secretion (including the submaximal secretion observed at supramaximal concentrations of agonist), and stimulation of glucose transport. Furthermore, CCK4 and CCK8 were able to comletely inhibit the binding of radioiodinated CCK33 to CCK receptors on acini. Therefore, the CCK4 sequence appears to be the minimal functional unit which possesses all of the information required to elicit the actions of CCK on the pancreas. The additional 4 amino acids present in CCK8 increase the affinity of the CCK molecule for pancreatic CCK receptors and thus enhance target organ specificity and sensitivity.

Scorpion Toxin-Induced Amylase Secretion in Guinea Pig Pancreas: Evidence for a New Neurotransmitter

Abstract Scorpion toxin, a substance that induces neurotransmitter release by depolarizing neurons, was used to stimulate amylase release from guinea pig pancreatic lobules. Scorpion toxin was found to act selectively on acinar cell neurons but not directly on acinar cells. The toxins action on lobules was blocked by tetrodotoxin, whereas scorpion toxin itself had no effect on isolated pancreatic acini. Toxin-induced amylase secretion from pancreatic lobules included two components, one that was atropine sensitive and one that was atropine resistant. This finding is consistent with the notion that scorpion toxin releases cholinergic and noncholinergic transmitters. Both cholinergic and noncholinergic effects showed a similar dose dependence, being maximal at a toxin concentration of 3 μg/ml. The noncholinergic pathway was not mediated through the CCK receptor since it was not blocked by dibutyryl cyclic GMP, a CCK antagonist. Moreover, the noncholinergic mechanism appeared to have a different biochemical mechanism of action than CCK in that scorpion toxin in the presence of atropine did not release rapidly intracellular Ca2+ prelabeled with 45Ca2+. The results suggest, therefore, the existence of a second neurotransmitter present in pancreatic nerve endings capable of stimulating amylase release in the guinea pig.