Evidence that hyperglycemia increases muscarinic binding in pancreatic islets of the rat.
We studied the effects of fasting and of diabetes on binding of [3H]methylscopolamine to pancreatic islets of the rat. In nondiabetic rats, fasting for 36 h decreased binding of the muscarinic antagonist by 33% (P less than 0.05). Fasting also abolished the insulin response to 10 microM acetylcholine. Diabetes was induced by injecting streptozotocin (STZ) neonatally in rats. At the time of the experiments (6-10 weeks of age) these rats exhibited hyperglycemia (12.6 +/- 1.0 vs. 7.1 +/- 0.3 mM blood glucose in nondiabetics) but had a normal weight. Relative to islets from age- and sex-matched nondiabetic rats, islets from STZ rats were smaller (0.7 +/- 0.1 vs. 1.9 +/- 0.2 nl islet volume) and contained less insulin (218 +/- 33 vs. 1390 +/- 71 microU/islet). When calculated per islet volume, binding of [3H]methylscopolamine to STZ islets was enhanced by 80% in comparison to binding to normal islets (P less than 0.001). Scatchard analysis indicated that enhanced binding was due to increased number of binding sites. Cholinergic-induced insulin release, as assessed by carbamylcholine, was 37% higher in STZ than in normal islets (P less than 0.05) when expressed per islet volume and 3- to 4-fold enhanced in STZ islets when expressed per islet insulin content. Insulin treatment of STZ rats for 3 days lowered blood glucose, diminished binding of [3H]methylscopolamine, and abolished carbamylcholine-induced insulin secretion. We conclude that the level of glycemia in vivo participates in the regulation of the number of muscarinic receptors in the pancreatic islet and that such regulation is associated with changes in cholinergic-induced insulin secretion.
Ostenson
C G
CG
Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden.
Grill
V
V
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism / Q000627:therapeutic use; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D019832:N-Methylscopolamine; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000378:metabolism
D007328:Insulin; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D002217:Carbachol; D000109:Acetylcholine; D019832:N-Methylscopolamine