Diabetes in the rat is associated with a reversible postreceptor defect in cholecystokinin action.
Diabetes in the rat is associated with a selective decrease in the sensitivity of pancreatic acini to the secretagogue cholecystokinin. In these animals the concentration of cholecystokinin-33 that maximally stimulates amylase release from isolated pancreatic acini shifts from 300 pM in normal animals to 1 nM in animals made diabetic with streptozotocin. To evaluate the role of the cholecystokinin receptor in this loss of sensitivity, specific 125I-cholecystokinin-33 binding to its receptors on acini was measured. When compared with controls, acini from diabetic rats bound more cholecystokinin at all hormone concentrations. In diabetes, the total cholecystokinin binding capacity of acini increased from 157 fmol/mg to 362 fmol/mg acinar protein. Moreover, the amount of cholecystokinin bound at a maximally stimulating cholecystokinin concentration increased fourfold from 11 to 44 fmol/mg acinar protein. When diabetes was reversed by treatment with insulin, both the altered secretory responses and the increased binding of 125I-cholecystokinin returned to normal. These data indicate, therefore, that the decreased sensitivity of pancreatic acini from diabetic rats is due to an impaired ability of receptor bound cholecystokinin to initiate its cellular response.
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002766:Cholecystokinin / Q000378:metabolism / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000627:therapeutic use; D007457:Iodine Radioisotopes; D008297:Male; D010179:Pancreas / Q000201:enzymology / Q000378:metabolism*; D010666:Phenylpropionates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011949:Receptors, Cholecystokinin
D007328:Insulin; D007457:Iodine Radioisotopes; D010666:Phenylpropionates; D011956:Receptors, Cell Surface; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin; C042561:N-succinimidyl 3-(3-hydroxy-5-iodophenyl)propionate; D000681:Amylases